South Sudan has borne the brunt of years of chronic warfare and probably has the highest malaria burden in sub-Saharan Africa. However, effective malaria control in post-conflict settings is hampered by a multiplicity of challenges. This manuscript reports on the strategies, progress and challenges of malaria control in South Sudan and serves as an example epitome for programmes operating in similar environments and provides a window for leveraging resources.To evaluate progress and challenges of the national malaria control programme an in-depth appraisal was undertaken according to the World Health Organization standard procedures for malaria programme performance review. Methodical analysis of published and unpublished documents on malaria control in South Sudan was conducted. To ensure completeness, findings of internal thematic desk assessments were triangulated in the field and updated by external review teams.South Sudan has strived to make progress in implementing the WHO recommended malaria control interventions as set out in the 2006–2013 National Malaria Strategic Plan. The country has faced enormous programmatic constraints including infrastructure, human and financial resource and a weak health system compounded by an increasing number of refugees, returnees and internally displaced people. The findings present a platform on which to tailor an evidence-based 2014–2018 national malaria strategic plan for the country and a unique opportunity for providing a model for countries in a post-conflict situation.The prospects for effective malaria control and elimination are huge in South Sudan. Nevertheless, strengthened coordination, infrastructure and human resource capacity, monitoring and evaluation are required. To achieve all this, allocation of adequate local funding would be critical. In 2010, about 219 million malaria cases and 660,000 deaths were reported globally. The disease remains a major cause of morbidity and mortality, exacting its greatest toll in sub-Saharan Africa where over 80% of cases and 90% of deaths occur. InterveSouth Sudan has borne the brunt of years of chronic liberation warfare from the time of Sudan’s independence from Anglo-Egyptian rule in 1956. The warUpon the signing of the CPA, South Sudan has been characterized by enormous infrastructure, human and financial resource constraints and a weak health system against a huge burden of diseases. The couThe malaria control situation is threatened by the impact of refugees, returnees, internally displaced populations, and natural disasters, i.e. flooding, that put added strain on an already weakened system from years of conflict and that may destabilize whatever gains that have been made. Given gross constraints to access and the austerity budget announced by the government, humanitarian need remains very high. It is estimated that out of a projected population of 11.1 million people, 40% of the population (4.5 million people) are in urgent need of humanitarian assistance. While STo reduce the malaria burden, the World Health Organization (WHO) recommended case management and vector control tools have been implemented expansively in South Sudan. To be aIn March 2012, South Sudan undertook an in-depth review of the national malaria control programme (NMCP). The dec2 of land mass, between 8° and 18° degrees south latitude and between 20° and 35° degrees east longitude, divided into 10 states with a total population of about 8.3 million[South Sudan is a land-locked country in East Africa, bordering six malarious countries: Central African Republic in the west, Democratic Republic of Congo in the southwest, Ethiopia in the east, Kenya and Uganda in the south and Sudan in the north, Figure . The cou million. The staA comprehensive assessment was undertaken according to the WHO standard procedures for Malaria Programme Review (MPR). The evaMalaria is the leading cause of morbidity and mortality in the country, accounting for 20% to 40% morbidity with over 20% of deaths reported at health facilities and 30% of all hospital admissions. The disPlasmodium falciparum, the most virulent parasite species is dominant and responsible for up to 94% of all morbidity, 5% is caused by Plasmodium vivax, 0.7% is due to Plasmodium malariae, and mixed infections occur in 6.3% of cases especially in the Greater Equatoria region[Anopheles gambiae s.s., Anopheles arabiensis and Anopheles funestus, with Anopheles nili as a secondary vector but little is known about their relative distribution in time and space[a region. The majnd space.The eco-epidemiological profile of South Sudan is ideal for proliferation of malaria vectors and country-wide perennial malaria transmission with seasonal variations. Malaria transmission season is longer in the southern than in the northern regions and peaks towards the end of the rainy season in September to November.Plasmodium falciparum resistance to CQ and SP were found ranging from 40% to 93% for CQ and 15% to 69% for SP, and the country switched its treatment policy to ACT[Anti-malarial drug efficacy studies for chloroquine (CQ) and sulphadoxine-pyrimethamine (SP) have been conducted across the three greater regions of the country between 2001 and 2003. High levels of y to ACT. Follow y to ACT.Anopheles species populations to DDT and deltamethrin in four localities of Juba County, Central Equatoria State. According to the WHO criteria, susceptibility was detected in Bari and Juba payams and suspected resistance in Munuki and Kator payams to 4% DDT, resistance was detected in Bari payam, and suspected resistance in Munuki, Katour and Juba payams to 0.05% deltamethrine[Anopheles species to identify malaria vectors. Insecticide resistance monitoring and surveillance system is being established.There is very limited data on insecticide resistance in malaria vectors in South Sudan. The only available information is on insecticide susceptibility of methrine. The stuThe MoH through the NMCP is responsible for planning, coordinating, implementing and monitoring of malaria control interventions. While the NMCP in South Sudan is relatively young, the malaria control policy and strategic framework is well defined, with key WHO recommended interventions being scaled up and monitoring and evaluation systems established Table . A natioHistorically, vector control was operationally harnessed for malaria prevention in South Sudan. In the late 70s and early 80s IRS and larviciding were implemented by the local vector control units to prevent malaria transmission in and around the major towns and municipalities. However, due to the collapse of infrastructure and public services these interventions stopped in 1983 and are currently not available at operational level. With thThe recommended channel for delivering Malaria in pregnancy (MIP) interventions is through comprehensive and focused ante-natal care (ANC) services with a three-pronged package; effective treatment of malaria and anaemia, IPT and use of LLINs. AccordiEffectual case management, consisting of definitive diagnosis and prompt treatment with appropriate anti-malarials, is a key strategic intervention for malaria control. In South Sudan, the malaria diagnosis policy recognizes microscopy as the gold standard for parasitological confirmation. However, due to constraints in human resource and institutional capacity microscopy is mostly restricted to hospital and primary health care centre (PHCC) levels. Malaria rapid diagnostic tests (RDTs), First Response Malaria HRP-2®, remain frontline confirmatory tools at the primary health care unit (PHCU) level and to lesser extent at the hospital and PHCC levels. With only 40% of the health facilities capable of offering definitive diagnostic services, most maResistance to CQ and SP in the country was detected between 2001 and 2004, limitinThe recommended treatment for severe malaria is parenteral artesunate with parenteral artemether and parenteral quinine as alternatives. The parenteral anti-malarials are given for at least 24 hrs after which an oral medication (ACT or quinine) would be given to complete treatment if the patient is able to take medication orally. The pre-referral treatment for severe malaria is rectal artesunate along with supportive treatment; tepid sponging, sucrose, and analgesics. Public-Private Partnership mechanisms have been put in place to enable the private sector to conform to national malaria treatment policies and guidelines.The NMCP collects routine morbidity case data from all health facilities monthly based on the national HMIS and the IDSR. There exist marked variations in reported malaria cases probably due to gross under - or over -estimations resulting from weak reporting systems Figures  and3. CLongitudinal measurement of progress in malaria control interventions has been provided by the South Sudan House Hold Survey (SHHS) and the Under the financial and technical auspices of the WHO, 32 malaria sentinel sites with at least 3 per state have been set up and operationalized covering all 10 states across the country. At each sentinel health facility, tracked indicators include: Number of uncomplicated malaria cases; number of severe malaria cases; malaria case fatality rates; number of uncomplicated malaria cases treated with first line anti-malarial; percentage of pregnant women who receive two doses of SP for IPTp; Blood smear and RDT positivity rates; severe anaemia rates and blood transfusion rates among children under five years of age; including stock levels and consumption rates for antimalarial – ACT, SP, injectable quinine, injectable artesunate. With recent funding from USAID, sentinel site surveillance is being strengthened. Malaria drug efficacy monitoring has been conducted from 2001 to 2003 by the MSF. Follow The NMCP in South Sudan started in 2004 as part of the Secretariat of Health based in Nairobi, Kenya. Since the signing of the CPA in 2005, major milestones in the fight against malaria have been achieved  with extension to 2013 has been implemented in South Sudan. Under tThe major funders of the malaria control in South Sudan are the Global Fund, WHO, UNICEF and USAID. Other contributors include the World Bank, MSH, DFID, PSI, Malaria Consortium and CIDA. The parThe decades of war in South Sudan virtually led to the collapse of the entire health system, as evidenced by the poor health outcome indicators of the country that are among the worst globally. The sitAmidst the austerity budget announced by government, humanitarian aid providers i.e. UN agencies, IOM and NGOs continue to play a pivotal role in malaria control. In 2013 about 131,990 conflict-related displacements occurred in South Sudan. These often over-clouded and mobile populations create a major stumbling block to malaria control. The country is not uniformly amenable for malaria control. In the northern states of Northern Bahr el Ghazal (NBeG), Unity and Upper Nile, control is challenged by an influx of South Sudanese returnees  and more than 224,000 refugees . Lack of access due to either conflict in Unity and Jonglei states or natural disaster like floods in Jonglei, Lakes, NBeG, Unity, Upper Nile and Warrap are also major impediments to control[While technical capacity for exploiting the full potential of IVM exists, financial and human resources to facilitate deployment of a full package of vector control tools are inadequate. There is minimal coordination among partners and a lack of adequate entomological and epidemiological data for rational evidence-based decision making for vector control at state and county levels Table . The funDespite the introduction of ACT as fixed dose at health facility and community level, access to diagnosis and treatment remains a constraint due long distances to health facilities, lack of functional microscopes, and stock-outs of RDTs and anti-malarials. Although progress has been made in ICCM, coverage and coordination remains minimal. The situation is further aggravated by challenges of ensuring correct practices in the largely unregulated private sector coupled with unavailability of treatment guidelines and algorithms. Most malaria cases are treated based on clinical suspicion due to limited diagnostic capacity. The parasites have developed resistance to CQ and SP. Currently there exists an uncoordinated supply chain operated by multiple partners. Procurement and supply chain management is further compromised by the non-existence of accurate consumption data on malaria commodities and the weak pull-based distribution system. The state of most storage facilities does not meet prescribed basic standards.There is insufficient qualified staff for M and E at all levels of the health system. Most health facilities have poor infrastructure and frequently experience stocks out of key supplies. They lack adequate reporting tools and health worker skills thus compromising quality and resulting into poor data recording and delayed or non -reporting. The county and state levels have limited capacity for supportive supervision and analysis and interpretation of data collected from the health facilities to provide timely corrective feedback. The national level has inadequate funding, lack a database and transport to allow implementation of the plans and to support the lower level structures. The MIP component is the least developed aspect of malaria control in South Sudan and is characterized by lack of access to and late attendance of pregnant women at ANC services. Unavailability of national training modules including limited research on prevention and treatment of MIP present an additional challenge.Coordination with other departments within the MoH and partners is weak leading to duplication of activities, inequitable distribution of partner support and difficulties in collection and collation of information. This has limited effective harmonization and sharing of messages and materials for BCC, minimal involvement and commitment of community leaders, private sector and government line ministries. As such, the target audience’s uptake of recommended practices to prevent and treat malaria remains low. There is limited human resource capacity with no clear structure at state and county level for malaria control. The minimal financial and technical capacity and high donor dependency has resulted in limited Government funding and inadequate support for operations Table .Following the call by the WHO for scaled-up malaria control efforts, coupledP. falciparum malaria from 2003 through 2008 showed a precipitous decline and a steady re-emergence through 2012  in reporting. Parasitological confirmation before treatment with antimalarials increased from 27% in 2009 to 40% in 2011. TherefoThe prevalence has been shown to be higher in the Greater Equatoria, followed by the Greater Bahr el Ghazal and lower in the Greater Upper Nile Regions of South Sudan. There iEffective deployment of conventional key malaria vector control interventions is mostly challenged in conflict and post-conflict situations. In South Sudan prevention of malaria in pregnant women and children through distribution of ITNs, IPT, RDTs and treatment with ACT has been prioritized including ICCM. With the increasing influx of mobile displaced populations, humanitarian groups have used these strategies for emergency response among refugees and returnees with striking efficacy. However, logistical assessments are critical for the correct quantifications of malaria commodities. Recently Mentor Initiative an NGO has embarked on IRS deployment with remarkable impact on the burden of malaria. This substantiates the premise that IRS is amenable and effective in emergency situations.South Sudan has one of the highest malaria burdens in sub-Saharan Africa; the disease remains a leading cause of morbidity and mortality in the country. This coMalaria control problems are further compounded by limited supply of health services due to a serious lack of qualified staff; inadequate equipment and supplies; long distances to facilities, poor roads and transport; dysfunctional referral system and cultural and financial barriers. Presently, only 44% of the population has access to health services within 5 km walking distance in South Sudan. The preWhile appreciable progress has been made relative to the 2006–2013 malaria control strategic plan  and various NGOs have also contributed considerably. Apart from 13 million USD allocated to malaria control in 2007/8 under the Multi Donor Trust Fund, domestic funding for health including malaria control has not been significant and has steadily dropped from 7.9% in 2006 to 4.2% in 2010[The health sector in South Sudan requires substantial technical, programmatic, managerial and financial input and investment. To move out from humanitarian assistance into development country-level sustainable programming and ensure allocation of adequate local funding, malaria control in South Sudan is prioritized under the Basic Package of Health Services (BPHS) which provides the operational reference for the implementation of the Health Policy and HSDP for the period 2011–2015. The BPHS is a key document for all stakeholders and is the platform for the cooperation between the implementing and capacity building partners. The HSDP is closely linked to the health section in the social and human development pillar of the South Sudan Development Plan (SSDP). This policy framework for health service delivery would increase advocacy and convince donors and parliament members to fund malaria control when faced with food insecurity and the necessity of meeting other essential needs, such as shelter and economic livelihoods for the thousands of returnees and those currently displaced.Prospects for effective malaria control and elimination in South Sudan are huge Table . HoweverSouth Sudan has dealt with constant threats from an influx of returnees, refugees, IDPs, flooding, and civil strife. Given the trend and magnitude of the malaria burden in the country a more defined malaria control strategic direction will be critical. To improve services in a post-conflict setting with, elements of conflict and severe resource limitations, there is need to address the increasing malaria case load through deployment of interventions that are amenable to the local situation and improve case detection, data analysis and reporting. A clear understanding of the effectiveness of control tools and improved health information system with integration of community is necessary. All this calls for improved requisite infrastructure and strengthened human and financial resource capacity in South Sudan.ACT: Artemisinin-based combination therapy; AS: Artesunate; AQ: Amodiaquine; CES: Central equatoria state; CPA: Comprehensive peace agreement; DHIS: Demographic health information survey; EES: Eastern equatoria state; EPI: Expanded programme for immunization; FBO: Faith-based organizations; GoSS: Government of southern Sudan; HMM: Home management of malaria; HMIS: Health management information system; HRP-2: Histidine rich protein-2; HSDP: Health sector development plan; HSSP: Health sector strategic plan; ICCM: Integrated community case management; IDSR: Integrated disease surveillance response; IMCI: Integrated management of childhood infections; IMA: Interchurch medical assistance; IOM: International organization for migration; IPT: Intermittent preventive treatment; IRS: Indoor residual spraying; LLINs: Long-lasting insecticidal nets; MDGs: Millennium development goals; MIP: Malaria in pregnancy; MIS: Malaria indicator survey; MoH: Ministry of health; MPR: Malaria programme review; MSF: Médecins Sans Frontières; NBeG: Northern Bahr el Ghazal; NGOs: Non-governmental organizations; NMCP: National malaria control programme; OPD: Out-patient department; PHCC: Primary health care centre; PSM: Procurement and supply chain management; RBM: Roll back malaria; RDTs: Rapid diagnostic tests; RSS: Republic of south Sudan; SHHS: Sudan house hold survey; SP: Sulpadoxine-pyrimethamine; UNICEF: United nations international children emergence fund; UNS: Unity state; USAID: United States agency for international development; WBeG: Western Bahr el Ghazal; WES: Western Equatoria state; WHO: World health organization; WRP: Warrap state.The authors declare that they have no competing of interests.HP: Managed the NMCP in South Sudan. MJ, AJ and CD: Coordinated deployment of malaria control interventions. BS, MY: monitored and evaluated the interventions. SPB: Collaborated. EC: Conceived the idea and wrote the paper. All authors read and approved the final manuscript.


To the Editor: Contagious caprine pleuropneumonia is a severe respiratory disease of goats caused by Mycoplasma capricolum subsp. capripneumoniae (Mccp), a member of the M. mycoides cluster (Pantholops hodgsonii) in China.In 2000, the International Union of Conservation of Nature first listed the Tibetan antelope as an endangered species , we analyzed a 562-bp segment of the H2 gene of Mccp, which was used to distinguish the Mccp and Mcc as reported by Lorenzon et al. (To assess the relationship of the Mccp strain isolated from infected Tibetan antelope with previously isolated Mccp strains and the closely related n et al.  Figure 2The changing habitat of endangered Tibetan antelope may lead to increased exposure to Mccp, which can cause devastating outbreaks, such as the one reported here. Goats and sheep are herded on grasslands at an altitude of 4,300–5,000 m, the same area where Tibetan antelope reside. Goats are a reservoir for Mccp, and Mccp has been isolated from sheep in mixed herds with goats (Our results show that contagious caprine pleuropneumonia may pose a substantial threat to the survival of endangered Tibetan antelope. Surveillance for Mccp infection among Tibetan antelope populations and domestic and wild goat and sheep populations that have close contact with the Tibetan antelope should be considered.Histopathologic findings and results of pathogen testing, primer pairs used for pathogen testing, lung tissue findings, and phylogenetic tree.


Organizational improvement of neonatal intensive care units requires strict monitoring of preterm infants, including routine assessment of physiological functions of the gastrointestinal system and optimized procedures for the definition of appropriate discharge timing.We conducted a prospective study on the effect of osteopathic manipulative treatment in a cohort of N = 350 consecutive premature infants admitted to a neonatal intensive care unit without any major complication between 2005 and 2008. In addition to ordinary care, N = 162 subjects received osteopathic treatment. Endpoints of the study were differences between study and control groups in terms of excessive length of stay and gastrointestinal symptoms, defined as the upper quartiles in the distribution of the overall population. Statistical analysis was based on crude and adjusted odds ratios from multivariate logistic regression.Baseline characteristics were evenly distributed across treated/control groups, except for the rate of infants unable to be oral fed at admission, significantly higher among those undergoing osteopathic care (p = .03). Osteopathic treatment was significantly associated with a reduced risk of an average daily occurrence of gut symptoms per subject above .44 . Gestational age lower or equal to 32 weeks, birth weight lower or equal to 1700 grams and no milk consumption at admission were associated with higher rates of length of stay in the unit of at least 28 days, while osteopathic treatment significantly reduced such risk .In a population of premature infants, osteopathic manipulative treatment showed to reduce a high occurrence of gastrointestinal symptoms and an excessive length of stay in the NICU. Randomized control studies are needed to generalize these results to a broad population of high risk newborns. Significant improvements in neonatal technology utilized in neonatal intensive care units (NICUs) over the last 2 decades, along with evidence-based care guidelines, have significantly improved hospitalization and survival for both low birth weight (LBW) infants and the residual preterm population, albeit at a high cost. A major proportion of pediatric hospital stays in the United States is attributable to neonatal conditions that rank among the most expensive items in the list of services provided for children . The aveLength of stay (LOS) in NICUs is strongly associated with GA and birth weight . InfantsHowever, compared to term infants, premature infants are unique in their need to attain not only medical stability but also physiologic maturity, including adequate temperature control, cessation of apnea and bradycardia, and adequate feeding behavior, before they are safely discharged to home ,6.Patterns of hospitalization of preterm infants are also associated with the presence of clinical symptoms of abnormal gastrointestinal function. In particular, vomit and regurgitation were found to be associated with increased esophageal acid occurrence among NICU patients , as wellIn VLBW infants, feeding tolerance algorithms are based on pre-prandial GR volume measurement. High pre-prandial volumes of GR are regarded as significant markers of feeding intolerance . PreviouNon invasive treatments to improve feeding tolerance and to reduce clinical complications of premature infants may represent a convenient option in the absence of standard procedures for specific subgroups of patients.The present report describes the activity of a research team investigating the effects of Osteopathic Manipulative Treatment (OMT) in preterm infants, including monitoring of physiological functions of the gastrointestinal system and LOS.To evaluate the efficacy of OMT on premature infants during hospitalization. Endpoints of the study were differences between study and control groups in terms of changes in gastrointestinal function and LOS.Primary endpoints were measured over the entire period of NICU hospitalization as follows:I. High frequency of gut symptoms, defined as the upper quartile of the average number of episodes of vomit, regurgitation, GR and enema per measurement visit per subject.II. Excess duration of LOS, defined as the upper quartile of LOS in NICU per subject.The study was based on a non randomized, longitudinal observational design investigating outcomes in a cohort of newborns admitted to the NICU of the main public hospital in Pescara, Abruzzo, Italy.Eligible subjects included all infants consecutively admitted between January 2005 to June 2008 (N = 663). A total of N = 359 passed the following exclusion criteria: GA less than 29 weeks, or greater than 37 weeks; osteopathic treatment performed more than 14 days after birth; newborn transferred to/from other hospital/unit; newborn from an HIV seropositive and/or drug addicted mother; newborn with any of the following clinical conditions: genetic disorders, congenital abnormalities, cardiovascular abnormalities, neurological disorders; proven or suspected necrotizing enterocolitis with or without gastrointestinal perforation; proven or suspected abdominal obstruction; pre- and/or post- surgery patients; pneumoperitoneum and/or atelectasis. Among the 304 subjects excluded, 232 infants had a GA below 29 or above 37, while 78 subjects presented with severe clinical conditions.After enrollment, 4 additional infants were dropped because of an unrecorded birth weight, and 5 infants  because of complications arising during hospitalization.The final total number of infants analyzed in this study was 350.A total of 188 preterm infants were non-randomly assigned to routine neonatal care; while 162 subjects received routine care plus OMT. All patients from both groups were transferred from the delivery and/or operating room to the NICU immediately after birth.No prior manipulation provided by any physical and/or massage therapist was performed on any infant.Data collection was performed by undergraduate osteopaths from the Accademia Italiana Osteopatia Tradizionale (AIOT). Measurements were recorded twice a week (Tuesdays and Fridays) based upon NICU's clinical charts completed by nursing staff who provided care on the same day.Additional infant information was included: date of birth, admission/discharge from NICU, GA at birth , birth weight at admission and discharge, formula and/or breast milk intake volume. Gastrointestinal function was measured as regurgitation , or vomiting , or GR finding , frequency of stooling and enema administration per patient care encounter. A neurological/developmental evaluation at entry/discharge was not available for this study as it does not constitute part of routine assessment in the NICU.Data were directly entered on an Excel spreadsheetOsteopathic treatment was administered to the intervention group on Tuesdays and Fridays. Subjects in the study arm received osteopathic care within 14 days after birth, regardless of the application of any other procedure .OMT was performed by a group of osteopaths certified by the Registro degli Osteopati d'Italia with at least five years of clinical experience.Treatment duration ranged between 20-30 minutes. The infant's entire body was evaluated and manipulative procedures were provided as indicated by the osteopathic palpatory structural examination results. Osteopaths performing OMT were trained to use only indirect and fluidic techniques which included: indirect myofascial, sutural spread, balanced membranous tension and balanced ligamentous tension .Feeding regimen, feeding strategies and enema administration were based on the application of standard international guidelines to both study arms ,15. As dPhysiological conditions required for discharge included: maintenance of body heat at room temperature, coordinated sucking, swallowing, and breathing while feeding; sustained pattern of weight gain; and stability of cardiorespiratory function  .Main results are expressed in terms of odds ratios between each level of a potential risk factor and a set reference category (R.C.), with primary endpoints classified as binary outcomes (low/high).Potential confounders included the following characteristics (categories): gender, GA , birth weight , oral feeding at admission (No/Yes).Univariate statistical tests included formal tests of the differences between study and control groups using chi-square for categorical variables and unpaired t-tests for continuous measurements.Multivariate logistic regression was used to estimate the independent effect of OMT on primary outcomes, simultaneously adjusting for all potential confounders. Statistical significance was based on a probability level (α) equal to 0.05. Results were expressed in terms of point estimates (odds ratios: OR) and 95% confidence intervals (C.I.). All analyses were performed using the statistical programming language R .Univariate statistical analyses are shown in Table Upper quartiles led to the definition of the following thresholds for the outcomes of interest:1) average daily occurrence of gut symptoms per subject above .44;2) LOS of at least 28 days.Results for gastrointestinal function are shown in Table Results for LOS are reported in Table The main objective of this exploratory study was to investigate the effects of OMT in a population of premature infants in terms of gastrointestinal functions and LOS.The medical literature lacks information of any potential benefits of complementary treatments in this area. To the best of the authors' knowledge, OMT in premature newborns has never been documented by pediatric specialty journals. Studies carried out in pediatric patients suggested positive effects of OMT in very young children -19. In tThe present study suggests that OMT may reduce the occurrence of frequent symptoms of abnormal gastrointestinal functionality.Precise mechanisms for such positive effects generated by OMT are difficult to specify, but several hypotheses can be offered on the basis of neurological, tissue and neuroendocrine factors.In terms of neurology, there is evidence of an association between autonomic nervous system function and OMT, showing a significant direct relation between myofascial release technique and modifications in the autonomic nervous system activity .Regarding the interaction between OMT and tissue modification, in-vitro models highlight a possible decrease in the production of inflammatory factors .A possible role of neuroendocrine factors can be hypothesized as indicated by the evidence of the effect of OMT on pain biomarker modification in patients affected by low back pain .This study also shows that a significantly higher rate of premature infants receiving osteopathic care can be discharged before 28 days regardless of gender, GA, birth weight and oral feeding at admission.Such a result may have important implications for the optimization of health care in premature infants. Focusing on the percentage of patients discharged before a given threshold, rather than looking at the average reduction in LOS, may be very relevant for health optimization and cost control. Reducing the rate of long stays would reduce the number of patients in the NICU, allowing for more cribs to become simultaneously available for those infants who require specialized care.From an epidemiological point of view, the potential benefit may also spread beyond discharge, considering that hospitalization can influence nutrition  and morbAn understanding of the differential advantage of OMT on specific subgroups, in particular within specified classes of GA, will require ad hoc studies with an adequate sample size. In the present study, it was not possible to perform subgroups analyses on subjects with very low GA, due to the very limited number of patients available for enrollment.Finally, some intrinsic limitations of the present study need to be outlined.This report is based on measurements implemented at the local NICU at the start of the study. Additional relevant confounding variables such as maternal/delivery factors (including breast feeding), respiratory support, method of feeding and gastric emptying time could not be included in this study.Treatment allocation was neither randomized nor structured, as it was based on matters of convenience within the constraints of the proposed two days per week of osteopathic care. Furthermore, due to the current logistics and procedures it was not possible to "blind" nurses and neonatologists to treatment regimen.This study, which was conducted in only one NICU, cannot capture the intrinsic variability of organizational strategies across multiple clinical centers managing the complexities of the overall population of newborn infants.From a methodological point of view, sample size was not based on formal power estimation, treatment was not allocated using a random procedure, and the population of preterm infants may not be representative of the entire population of cases.The above limitations affect our ability to check for bias and duly rely on the precision of our estimates. In other terms, both the size of the effect of OMT (point estimate) and its level of uncertainty  are more likely to be inconsistent with further results obtainable under more general conditions.To evaluate the efficacy of OMT more studies are required using formal experimental methods, such as randomized and placebo controlled clinical trials. The best endpoint of a well designed three armed study would be the difference between the sham and the actual treatment. However, to make it possible, osteopaths should collaborate with NICU managers to revise the application of operational procedures, so that OMT can be smoothly applied on large populations, across multiple clinical sites.Despite the above limitations, and given the current lack of information on the possible effects of OMT in preterm infants, the finding of this report sets an interesting ground for new developments. Among these, the standard measurement of all relevant parameters represents an essential aspect that deserves attention for future investigations. Key characteristics and outcomes that can be easily monitored on a daily basis by clinicians, nurses and even parents of preterm infants have been identified. Their adoption for the construction of electronic data base registers can offer a sustainable means to improve both analysis and management of NICU activity, allowing to carry out more detailed exploratory studies while providing a basis for ongoing trials.The study suggests that osteopathic treatment may reduce a high occurrence of gastrointestinal symptoms and the rates of long-term stays.Randomized control studies are needed to confirm these results and to generalize them to a broader population of high risk newborns.NICU: neonatal intensive care unit; VLBW: very low birth weight; LBW: low birth weigh; GA: gestational age; LOS: length of stay; GER: gastroesophageal reflux; GR: gastric residual; OMT: osteopathic manipulative treatment; OR: odd ratio.GB and CD conceived the idea of the study. GP, GB, VC, CR and FCE participated in the design of the study and its coordination. GP, PT, MD, FCE and PF coordinated and performed the data collection. GP and FCA drafted the manuscript. FCA performed the statistical analysis. All authors read and approved the final manuscript.The authors declare that they have no competing interests.


The facial pits of rattlesnakes, copperheads, lanceheads, bushmasters and other American and Asian pitvipers  are highly innervated and densely vascularized infrared (IR) receptor organs. For over a century, studies have focused on a small sample of model species from North America and Asia. Based on an expanded survey of Central and South American crotalines, we report a conspicuous accessory structure composed of well-defined papillae that project from the anterior orbital adnexa. The papillae are continuous with the inner chamber of the IR receptor organ and our histological and ultrastructural data suggest that they possess a well-developed nervous network and extensive vascularization; however, they lack the characteristic IR-sensitive terminal nerve masses found in the IR-receptive pit membrane. The function of the IR receptor organ papillae is unknown. Rattlesnakes, copperheads, lanceheads, bushmasters and other American and Asian pitvipers  are uniquely characterized by possessing a deep facial pit in the loreal region between the eye and naris . Since NGloydius and Trimeresurus from Asia, Agkistrodon and Crotalus from North America), with little or nothing known about IR receptor organs of the remaining 200 species of crotalines. While conducting an expanded survey of the IR receptor organ in Central and South American crotalines, we discovered a new accessory structure that is extensively innervated, highly vascularized, and continuous with the IR receptor organ but that lacks the IR-sensitive TNMs present in the pit membrane.Previous studies of IR receptor organ structure and function focused on only a few species of four genera , fixed samples were also dehydrated in ethanol and embedded in glycol methacrylate (Leica). Sections (3–4 µm) were cut in a Leica RM 2255 microtome and stained with toluidine blue-fuchsin 2 as an intermediate medium, and coated with gold in a sputtering device. Samples were examined in an FEI Quanta 250 scanning electron microscope, operating at 10–12.5 kV. For transmission electron microscopy (TEM), the samples were post-fixed in 1% osmium tetroxide, dehydrated and embedded in epoxy resin. Ultrathin sections were cut in a Leica UC7 ultramicrotome, contrasted in 2% uranyl acetate and lead citrate and examined in a LEO 906E electron microscope operating at 80 kV.For convenience, we follow the generic taxonomy of Fenwick et al. Atropoides nummifer ; Agkistrodon piscivorus ; Bothriechis schlegelii ; Bothriopsis bilineata ; Bothriopsis taeniata ; Bothrocophias hyoprora (MZUSP 5293); Bothropoides alcatraz (MZUSP 1453); Bothropoides jararaca (MZUSP 5252); Bothrops asper ; Bothrops brazili ; Bothrops jararacussu (MZUSP 14923); Crotalus durissus ; Lachesis muta ; Ovophis okinavensis ; Porthidium lansbergi ; P. nasutum ; Rhinocerophis alternatus (MZUSP 1458); R. cotiara (MZUSP 2504).Dissecting microscopes were used for gross examination of duct openings of the following specimens : Permission was obtained from all the relevant museums/institutions to access the collections and specimens were either loaned or examined at the museum/institution.Bothriopsis, Bothrocophias, Bothropoides, Bothrops, Lachesis, Porthidum, and Rhinocerophis the orbital opening of the inner chamber duct lies deep in the orbit and is encircled by well defined cuneiform papillae that vary in length from greatly enlarged folds to elongate, externally visible projections emerging from the anterior corner of the orbit (Agkistrodon piscivorus, Atropoides nummifer, Bothriechis schlegelii, Crotalus durissus, and Ovophis okinavensis is a simple preocular opening in the superficial orbital adnexa, immediately beneath the preocular scales, which is consistent with previous observations We examined the gross morphology of the IR receptor organs of 18 species of pitvipers representing the phylogenetic diversity of Neotropical lineages and one Asian genus. In all examined species of the Neotropical genera he orbit . In contLM and SEM revealed that the surface of the papillae is flat , with thBothrops asper showed that the papillae are covered by an epithelium composed of two layers of cells and a cornified superficial layer (B. asper shows the same general pattern described previously LM and TEM of the papillae of al layer , 3A. Theal layer  and an eal layer . Melanopal layer . The IR-The function of the IR receptor organ papillae is unknown. In general, papillae and papilla-like structures increase surface area to fulfill a variety of sensory and physiological functions. Despite the considerable increase in epithelial surface area, there is no evidence that papillary tissues or cells are used for absorption. Likewise, there is no indication of a secretory function associated with either isolated cells or clusters of cells or of any storage of secretory compounds. Primarily chemoreceptive and mechanoreceptive/tactile functions are possible but seem unlikely given the location of the papillae in the anterior corner of the orbit. Given their position around the orbital opening of the inner chamber duct, the papillae could serve as a physical barrier to prevent debris or ectoparasites from entering the inner chamber and interfering with IR detection while still allowing inner chamber pressure to equalize. However, this hypothesis is inconsistent with their extensive vascularization and and thin epithelium.The fact that the papillae are projections of the IR receptor organ into the environment from the orbit suggests they might be related somehow to IR-reception, possibly functioning as a second IR detector that provides an independent reference point to complement the information obtained by the pit membrane. The extensive vascularization of the papillae, which is necessary for energy and oxygen demands and rapid heat exchange in the IR-receptive pit membrane Gloydius and Trimeresurus and the North American genera Agkistrodon and Crotalus—none of which possess papillae; does IR reception differ between species that possess and lack IR receptor organ papillae? Despite recent efforts to elucidate viperid phylogeny Clearly, the discovery of this accessory structure of the pitviper IR receptor organ raises more questions than can be answered presently. If the IR receptor organ papillae are directly involved in IR reception, how do they accomplish this function without IR-sensitive TNMs? And if they are not directly involved in IR reception, then what function do they perform? Previous studies of IR receptor organ structure and function focused on only a few species of the Asian genera


Parrotfishes and surgeonfishes perform important functional roles in the dynamics of coral reef systems. This is a consequence of their varied feeding behaviors ranging from targeted consumption of living plant material (primarily surgeonfishes) to feeding on detrital aggregates that are either scraped from the reef surface or excavated from the deeper reef substratum (primarily parrotfishes). Increased fishing pressure and widespread habitat destruction have led to population declines for several species of these two groups. Species-specific data on global distribution, population status, life history characteristics, and major threats were compiled for each of the 179 known species of parrotfishes and surgeonfishes to determine the likelihood of extinction of each species under the Categories and Criteria of the IUCN Red List of Threatened Species. Due in part to the extensive distributions of most species and the life history traits exhibited in these two families, only three (1.7%) of the species are listed at an elevated risk of global extinction. The majority of the parrotfishes and surgeonfishes (86%) are listed as Least Concern, 10% are listed as Data Deficient and 1% are listed as Near Threatened. The risk of localized extinction, however, is higher in some areas, particularly in the Coral Triangle region. The relatively low proportion of species globally listed in threatened Categories is highly encouraging, and some conservation successes are attributed to concentrated conservation efforts. However, with the growing realization of man's profound impact on the planet, conservation actions such as improved marine reserve networks, more stringent fishing regulations, and continued monitoring of the population status at the species and community levels are imperative for the prevention of species loss in these groups of important and iconic coral reef fishes. Parrotfishes  and surgeonfishes (Acanthuridae) are among the most conspicuous and dominant groups of fishes on coral reefs, both in terms of numbers of individuals and biomass Species in these two families have long been considered to play important functional roles in coral reef ecosystems. They exhibit a range of feeding modes and ingest a variety of food items including plant material, detritus/bacterial complexes, zooplankton, live coral, and sessile/benthic invertebrates Parrotfishes and surgeonfishes have been collectively categorized as herbivores Herbivorous fishes are considered to play an important role in coral reef dynamics by limiting the establishment and growth of algal communities that impede coral recruitment Bolbometopon muricatum), the largest of all parrotfishes and the largest coral predator, is considered an important bioeroder Chlorurus sordidus), there is a non-linear relationship between body size and ecological function, such that reefs impacted by fishing and dominated by small individuals may be functionally impaired The larger taxa of the excavating parrotfishes may especially have profound effects on the dynamics of reef growth and sedimentation B. muricatumScarus guacamaia) Many species of parrotfishes and surgeonfishes are prized components of coral reef fisheries in many parts of their wide distributional range, with a number of dedicated fisheries particularly in the Caribbean Zebrasoma flavescens) Z. flavescens is well monitored and is subject to a number of management actions including: marine reserves, Fish Replenishment Areas (FRAs), and establishment of a limited entry program for the aquarium fishery As iconic reef inhabitants, parrotfishes and surgeonfishes are also important components of marine park tourism and the diving industry. In addition, many are popular marine aquarium species, some of which are collected by the tens of thousands each year, such as the Yellow Tang  determine the global conservation status of these fishes, 2) draw attention to regional importance and the local threats affecting species in these two families, 3) highlight the habitat status of coral reef dependent species, and 4) underline life history traits that affect coral reef dynamics and predispose species to heightened risks of extinction.Acanthurus tractus, Sparisoma rocha, and Sparisoma choati) are currently under assessment and are not included in these results. Eastern Tropical Pacific endemics were assessed in 2008 Global Red List Assessments were conducted for the world's known parrotfishes and surgeonfishes using the International Union for Conservation of Nature (IUCN) Red List Categories and Criteria http://www.iucnredlist.org).Prior to the workshops, species-specific information on taxonomy, distribution, population status and trends, ecology, biology, life history, utilization, impacts of major threats, and conservation measures were compiled. During the Red List Assessment workshops, species were evaluated one at a time by regional and international experts, with outside consultation and follow-up conducted when additional information was needed but not available at the workshop. Based on the most current data, each species was assigned to one of eight levels of extinction risk expressed as an IUCN Red List Category There are eight different levels of extinction risk on the IUCN Red List Categories: Extinct (EX), Extinct in the Wild (EW), Critically Endangered (CR), Endangered (EN), Vulnerable (VU), Near Threatened (NT), Least Concern (LC), and Data Deficient (DD). A species is listed in one of the three threatened Categories  if it meets the thresholds and conditions for that category in one of the five different available criteria (A–E) . A categThe five Criteria underscore the real strength of the IUCN Red List as these quantitative thresholds are based on extinction risk theory and can be collectively applied across a range of taxonomic groups that exhibit diverse life histories Digital distribution maps were created in ArcView 3.3 based on drawing a minimum convex polygon connecting points of known species' occurrence. Since the majority of parrotfishes and surgeonfishes inhabit shallow waters in coral reef habitats, each species map was cut to a maximum depth of 200 m with a 100 km buffer from the coastline, based on 2 minute spatial bathymetry data available from NOAA National Marine Fisheries Service (ETOPO1). This “cookie-cutter” method allows the analyses to be standardized and is a better representation of the known occurrence of these groups that inhabit shallow waters To determine the number of species affected by fisheries, distribution maps for all species that were impacted by the fisheries threat , were overlain to create a richness map for this type of threat. The two other major threat codes that were assigned, if relevant, to species during the workshop process included habitat loss  and pollution (including climate change).The proportion of marine protected area within each species range was calculated in ArcGIS by first determining the total area of each species distribution map as described above. Each species distribution map was then overlain with the 2010 World Database of Protected Areas During Red List assessment workshops, participants assigned each species to one or more of the IUCN marine habitat classifications Functional classification based on dietary targets and both pre-and post-ingestive processes were determined for each species to more accurately portray the ecological features of these groups and their impact on different coral reef systems. Based on this information, each species was assigned to one of four feeding functional groups: detritivore, herbivore, omnivore, and planktivore In light of the susceptibility of parrotfishes and surgeonfishes to habitat degradation, coral reef habitat decline was estimated for each species. The percentage of destroyed and declining coral reef in a species' range was calculated based on estimates of effectively lost reefs and reefs at critical stages in each global geographic node as reported by Wilkinson (2008) Scarus trispinosus) listed as Endangered; Bolbometopon muricatum and Kapingamarangi Surgeonfish (Acanthurus chronixis) listed as Vulnerable. Of these three species, two are large-bodied, long-lived and experiencing significant population declines from intense fishing pressure. The third species, A. chronixis, has a restricted distribution known only from Kapingamarangi Atoll, Caroline Islands, and is also exploited by subsistence fishers. Two species, Bower's Parrotfish (Chlorurus bowersi) and the Yellowtail Parrotfish (Scarus hypselopterus), did not fully meet the thresholds and conditions provided in the Criteria for listing under a threatened Category, but were very close to these thresholds and were thus assessed as Near Threatened. A complete list of species, Red List Category and, associated information is provided in Of the 179 species assessed, only three qualified for listing under a threatened Category: the Greenback Parrotfish  were listed as Least Concern. These species have broad distributional ranges, high turnover rates, occur in a wide variety of habitats, and are close to the base of the food chain as these species feed on an array of sources that include plant materials, detrital aggregates, bacterial and meiofaunal complexes Scarus guacamaia, which was assessed as Data Deficient et al. (2005) S. guacamaia is locally extinct, this species is confirmed as a vagrant along the Brazilian coast. In the Caribbean, this species has experienced significant localized population declines from destruction and loss of its mangrove habitats and historical overfishing S. guacamaia appears to occur in high densities only in areas that are protected from fishing Of special concern is the largest parrotfish in the Atlantic, S. guacamaia shares a number of parallel traits with Bolbometopon muricatum, the largest parrotfish in the Indo-Pacific. Intrinsic life history characteristics such as large size, natural rarity and shallow foraging areas render both of these species particularly susceptible to overfishing mainly spearfishing. Both species recruit into very shallow water, sheltered reef and mangrove sites that are increasingly impacted by habitat modification and degradation. Scarus guacamaia is experiencing >30% decline, destruction of coral reef habitat (which makes up 7% of its range) and is exposed to extensive mangrove deforestation in many parts of its distribution. Unlike B. muricatum, which inhabits a wide oceanic basin and could find refuge on isolated oceanic islands in the Indo-Pacific, S. guacamaia inhabits a smaller oceanic habitat and may not have access to the types of refuge available for B. muricatum. For these reasons, S. guacamaia is likely to be conservation dependent, especially as recorded densities are highest only in areas where protection is present. In the absence or cessation of protective measures, S. guacamaia may currently qualify for a re-listing of Near Threatened, or possibly one of the threatened categories in the near future (within a period of 5 years).However, Bolbometopon muricatum, listed as Vulnerable, which is the largest of all the scarines, reaching 1.4 m (FL). Intrinsic life history characteristics exhibited by B. muricatum, such as large body size, nocturnal aggregating behavior in shallow lagoons, reef caves or coral structures, daytime foraging in shallow waters B. muricatum is heavily fished in most parts of its wide distributional range and is rare and virtually extinct at some locations  is listed as Least Concern globally but is assessed as Near Threatened in the Coral Triangle region. This species is heavily fished throughout the region, with recorded reductions of 50–60% in the Philippines from resource exploitation C. bleekeri also inhabits sheltered coral reef habitats that are under pressure from coastal development, pollution, and climate change Parrotfishes and surgeonfishes are important sources of protein in the Coral Triangle region and are commercially targeted with many species prominent in fish markets. Of the 105 species in the Coral Triangle, 18 are commonly targeted commercially in multi-species fisheries, with many more species actually present in catches. Of the commonly targeted species, 13 were at a higher risk of extinction regionally compared to their global assessment . For exaAdditional regional assessments are needed to better understand the conservation status of these species, thereby bringing to the forefront significant threats to the local populations that would not otherwise be captured at the global scale. A comprehensive regional assessment for all known species of marine bony and cartilaginous shorefishes, corals, mangroves, and seagrasses was conducted for the Tropical Eastern Pacific (TEP) Scarus persicus, but as a mixed habitat species known to inhabit rocky reefs and coral patches, it is not know to what extent it may actually be affected by coral reef loss (Scarus maculipinna), known only from reefs off of Thailand and Indonesia, may be significantly impacted by an estimated 60% coral reef habitat loss and decline within its range. However, this species was assessed as Data Deficient, as it was fairly recently described in 2007, and there is very limited information available on population status, abundance, or life history characteristics.The adverse effects of coral loss and habitat degradation  eef loss . By contA. chronixis). However, Chlorurus bowersi, listed as Near Threatened, has a relatively restricted range in the Indo-Pacific and is subject to intense fishing pressure in over 90% of its distribution. Fishing coupled with rampant habitat loss may prove detrimental to this species in the near future and warrant listing in a higher threat category. Interestingly, some Data Deficient and Least Concern species have as much as 60% coral reef decline and area loss within their range. These species currently listed in low extinction risk categories may necessitate listing at a higher level of threat as habitat loss and degradation persist within the species' range. Models of extrinsic threat factors may be used to predict probability of extinction in the future. Indeed, Davidson et al. (2012) The three threatened and Near Threatened species that are exclusive to coral reefs have a lower average proportion of destroyed and declining reef area within their ranges compared to those listed as Least Concern or Data Deficient . This loZ. flavescens recruit into live branching corals and areas of high coral cover Many parrotfishes and surgeonfishes exhibit strong associations with coral reefs, especially as live coral provide suitable habitat for juveniles of both groups, and several sub-adult and adult species of surgeonfishes are primarily associated with coral B. muricatum, the Bicolor Parrotfish (Cetoscarus bicolor), and other species of the genus ChlorurusWidespread coral reef loss and declining habitat conditions are particularly worrying for some corallivorous excavating parrotfishes, particularly Studies on the trophic ecology of herbivorous fishes have focused on the ecological impacts of these fishes on reefs, in particular, the contributions of herbivores in the prevention of macro-algal phase shifts in coral reef systems Acanthurus thompsoni and A. mata. Compared to herbivores and detritivores, members of the last two categories have limited impact on the benthic biota of the reef. Four of the five species listed in threatened or Near Threatened Categories are classified as detritivores.There is great diversity in feeding patterns exhibited by parrotfishes and surgeonfishes Of all the threats identified for parrotfishes and surgeonfishes, none compete with the pervasive and deleterious effects of fishing. At least 40% (73 species) were determined to be impacted by either small-scale or large-scale fisheries. Other threats affecting parrotfishes and surgeonfishes include habitat modification and degradation (6%), pollution (3%), or by-catch (1%) . The CorS. guacamaiaB. muricatumC. bowersiS. trispinosusThe effects of overfishing on the loss of large consumer species in marine ecosystems have been well documented Scarus rubroviolaceus), Steephead Parrotfish, Chlorurus microrhinos), Blue-barred Parrotfish (Scarus ghobban), and B. muricatum, the target is shifted to the smaller scraping species, e.g. Yellowbarred Parrotfish (Scarus dimidiatus), Globehead Parrotfish (Scarus globiceps), and Yellowband Parrotfish (Scarus schlegeli) Changes in size structures are key indicators of the effects of human disturbance Z. flavescens in Hawaii Acanthurus spp. and Naso spp. in the Philippines B. muricatum in Australia Calotomus zonarchus from the Hawaiian Islands and Prionurus microlepidotus from eastern Australia, both listed as Least Concern, currently have a large proportion (>45%) of their range within a protected area. By contrast, Acanthuris chronixis, listed as Vulnerable, is not protected within any marine protected area within its known range in the Caroline Islands.The principal conservation actions in place for parrotfishes and surgeonfishes are presence in marine reserves, and fisheries restrictions and limits. Marine reserves have been shown to facilitate recovery of populations of these key functional groups Scarus coelestinus), Blue Parrotfish (Scarus coeruleus), and S. guacamaia as well as reduced parrotfish harvest in St. Croix Because of the long recognized ecological services provided by the parrotfishes and surgeonfishes, species-specific management measures are in place in Bermuda, wherein all species of parrotfishes are protected under the Fisheries (Protected Species) Order 1978 Bolbometopon muricatum, Scarus guacamaia, etc.) that are present in areas of high fishing pressure and or high coral reef habitat loss, should be a priority for further research and monitoring, regardless of their IUCN Red List Category.Parrotfishes and surgeonfishes are critical components of coral reefs, a habitat that is experiencing extensive global decline B. muricatum, as the schooling behavior of this species in shallow waters makes it highly vulnerable to exploitation It is important to note that despite the prevalence of marine reserves, the effectiveness of these conservation efforts, is rarely measured, and enforcement is often weak or absent in many parts of the world. Urgent protection and effective protective legislation is needed as well as continued monitoring of harvest levels and population status, especially for those species already at increased risk of extinction. In addition to scaling up of species-specific conservation actions, existing conservation practices need to take into account the reproductive strategies of these species that render them vulnerable to extinction. Parrotfishes and surgeonfishes form spawning aggregations with at least 14 and nine confirmed aggregations for the Acanthuridae and scarinae respectively In order to afford adequate conservation of these species, critical knowledge gaps also need to be addressed. Although a number of demographic, trophodynamic, distribution, and habitat association studies have been conducted for both groups, there is a general lack of information, on life history, dietary requirements, fisheries information and trade data for most of the commercially targeted coral reef fishes Table S1Complete list of species, Red List Category and associated information on life history, dietary classification and presence in marine reserves.(PDF)Click here for additional data file.Table S2Percentage of coral reef loss and declining reef area for all species of parrotfishes and surgeonfishes .(PDF)Click here for additional data file.Table S3Major threats identified for each species of parrotfish and surgeonfish.(PDF)Click here for additional data file.


Impaired glucose metabolism has been linked with increased cancer risk, but the association between serum glucose and cancer risk remains unclear. We used repeated measurements of glucose and fructosamine to get more insight into the association between the glucose metabolism and risk of cancer.We selected 11,998 persons (>20 years old) with four prospectively collected serum glucose and fructosamine measurements from the Apolipoprotein Mortality Risk (AMORIS) study. Multivariate Cox proportional hazards regression was used to assess standardized log of overall mean glucose and fructosamine in relation to cancer risk. Similar analyses were performed for tertiles of glucose and fructosamine and for different types of cancer.A positive trend was observed between standardized log overall mean glucose and overall cancer risk . Including standardized log fructosamine in the model resulted in a stronger association between glucose and cancer risk and aninverse association between fructosamine and cancer risk . Cancer risks were highest among those in the highest tertile of glucose and lowest tertile of fructosamine. Similar findings were observed for prostate, lung, and colorectal cancer while none observed for breast cancer.The contrasting effect between glucose, fructosamine, and cancer risk suggests the existence of distinct groups among those with impaired glucose metabolism, resulting in different cancer risks based on individual metabolic profiles. Further studies are needed to clarify whether glucose is a proxy of other lifestyle-related or metabolic factors. Impaired glucose metabolism is one of the most common lifestyle-related disorders and has been linked to various chronic diseases including cancer Besides serum glucose, other markers of the glucose metabolism have been used to monitor diabetic patients. Fructosamine, which refers to glycated serum proteins, reflects the average glucose levels for the previous 10–14 days and thus serves as a more stable indicator of short-term glycaemic status compared to serum glucose The Apolipoprotein MOrtality RISk (AMORIS) study contains 351,487 men and 338,101 women recruited during the period 1985 to 1996, mainly from the greater Stockholm area From the AMORIS population, we selected all participants aged 20 or older who had four repeated measurements of glucose and fructosamine . To define a repeated measurement we used the following criteria: the interval between each measurement had to be at least 9 months but maximum 15 months, and the interval between the first and the fourth measurements could not exceed 45 months. These intervals were chosen to capture annual changes in glycaemic status. All participants were free from cancer at time of entry and none were diagnosed with cancer or died within three months after study entry. The variables regarded as exposures in this study were serum glucose (mmol/L) and fructosamine (mmol/L). Standardized logarithm of overall mean glucose and fructosamine were calculated to observe the effect of small changes in glucose and fructosamine levels. Since fructosamine levels may be affected by serum albumin, we also assessed corrected fructosamine (c-fructosamine) using the following formula: (fructosamine (mmol/L)/albumin (g/L))×100 The following data were also collected from the CALAB database: total cholesterol (mmol/L), triglycerides (mmol/L), and age at baseline. Height (cm) and weight (kg) were recorded for 2,828 (24%) subjects and used to determine body mass index (BMI). The mean total cholesterol and triglycerides levels recorded at the same time as the four glucose and fructosamine measurements were also calculated and used in the analysis. All laboratory examinations were performed with automated and calibrated instruments in CALAB laboratory Information regarding cancer diagnosis was obtained from Swedish National Cancer Register, using ICD-7 codes to identify overall (140–205), prostate (177), breast (170), colorectal , and lung cancer (162). From the Population and Housing Census, information about socioeconomic status (SES) was also collected. SES is based on occupational groups and classifies all gainfully employed subjects as manual workers and nonmanual workers, which are referred to below as blue collar and white collar workers st December 2002), whichever occurred first. All analyses were conducted with Statistical Analysis Systems (SAS) release 9.1.3 .Multivariate Cox proportional hazards regression was used to study the association between glucose, fructosamine, and cancer. We assessed the standardized log of overall mean serum glucose and fructosamine in relation to overall cancer risk using four different models. In the first model, we evaluated the association between standardized log of overall mean glucose or fructosamine and risk of cancer,while adjusting for age. Next, we assessed cancer risk while including standardized log of overall mean glucose and fructosamine in the same model and adjusting for age. Additional adjustment were subsequently conducted for other potential confounding factors including gender, SES, fasting status, history of cardiovascular and lung disease, history of diabetes, serum albumin, triglycerides and total cholesterol levels. Additionally, we performed a sensitivity analysis for persons aged 50 and older in the study population. To further minimize confounding effects by history of diabetes, we repeated the above analyses among all non-diabetic persons . These were defined as those with glucose <7.0 mmol/L at all measurements and without any registered hospital discharge diagnosis of diabetes prior to the fourth measurement. As obesity has also been linked to both impaired glucose metabolism and cancer During a mean follow-up of 9.4 years, 1,021 participants (8.51%) developed cancer. More cancers were observed in men (57.79%). An overview of the study population is given in When assessing the link between glucose, fructosamine and overall cancer risk in the first model, we only observed a positive association between standardized log of overall mean glucose and cancer . When we included both glucose and fructosamine in one model, we found a stronger association between glucose and cancer risk and a statistically significant inverse association between fructosamine and overall cancer . Further adjustments for potential confounders did not substantially alter these results , but no statistically significant association between fructosamine and cancer risk was found. In the subgroup with recorded BMI values and the subgroup who was fasting during all four measurements, we did not observe any relationship between glucose, fructosamine, and cancer risk . When coWhen studying specific cancers, we observed an inverse association between standardized log of overall mean fructosamine and risk of prostate, colorectal, and lung cancer when also taking into account glucose levels . No clear association was found between glucose, frucosamine and breast cancer risk. Finally, using likelihood ratio test, we found no statistically significant interaction between standardized log glucose and fructosamine in the above models .In order to test whether the subgroup with four repeated measurements differs from those with at least one glucose measurement in AMORIS, we studied this association in the subcohort of all persons aged >20 with a single measurement of glucose and fructosamine . As shown in The present study found an increased risk of cancer in persons with increasing glucose levels and decreasing fructosamine levels. We also showed that those in the highest tertile of glucose and lowest tertile of fructosamine combined were at the highest risk of developing cancer. Similar findings were observed for prostate, colorectal, and lung cancer.The generation of advanced glycation end products (AGEs) during nonenzymatic glycation of free amino group of proteins, lipids, or amino acids is one of the suggested mechanisms for the link between elevated serum glucose and cancer risk 1C has later taken over this role and is currently regarded as the gold standard for measurement of glycaemic control in diabetic patients 1C and cancer occurrence Fructosamine represents all glycated serum proteins and may therefore also be related to formation of AGEs and subsequent development of cancer 1C and fructosamine in turnover times. The 6 to 12 week time frame over which HbA1C equilibrates is important when comparing it with shorter-term measures as fructosamine 1C reflects non-enzymatic glycosylation in the intraerythrocyte compartment 1C is beyond the scope of this study.When interpreting the value of glucose and fructosamine as biomarkers, one should take into account the significant differences between measures of plasma glucose and glyceamia estimated from HbA1C identify further possible sources of population variation beyond glycaemic control per se. When diagnosing diabetes, postprandial glucose levels are more likely to detect diabetes in lean individuals, while fasting glucose levels are more likely to identify obese individuals The differences between fasting glucose, fructosamine and HbAet al. assessed the risk of breast and colorectal cancer in the Women’s Health Initiative Study using serum glucose as a time-dependent covariate and demonstrated a positive trend between glucose measured in different time frames and the risk of cancer To date, there have been few studies on repeated measurements of glucose metabolism markers in relation to cancer risk. Kabat In this study, an inverse relation between fructosamine and cancer risk was also observed for different cancer sites, i.e prostate, colorectal and lung cancer. However, most of the associations between glucose and risk of these individual cancers were not statistically significant, which may be caused by the small number of events in the study population. Additionally, such lack of association may occur due to other factors modifying individual cancer risk, such as menopausal status and hormone replacement therapy for breast cancer The major strength of this study is the large number of subjects with four prospectively collected measurements of serum glucose and fructosamine, all measured in the same laboratory. The use of national registers provided detailed follow-up information on diagnosis of cancer, time of death, and emigration for all subjects. To our knowledge, this is the first study using repeated measurements of glucose and fructosamine in assessing the risk of cancer, hence providing a more detailed and accurate overview of the glucose status of an individual. The AMORIS population was mainly selected by analyzing blood samples from healthy check-ups in non-hospitalized individuals. This healthy cohort effect is not thought to affect the internal validity of the current study and is likely to be minor since it has been shown that the AMORIS cohort is similar to the general working population of Stockholm County in terms of SES and ethnicity By using repeated measurements of glucose and fructosamine, the present study showed that higher levels of fructosamine contributed to a decreased risk of cancer as opposed to the effect of higher glucose levels on cancer risk. These discrepancies emphasize the complex relation between the glucose metabolism and cancer, which does not necessarily reflect the established link between diabetes and cancer. Instead, our findings highlight the existence of different cancer risk groups among those with impaired glucose metabolism, according to their individual metabolic profiles. Hence, further studies are relevant to understand whether glucose levels are associated with cancer risk as markers of lifestyle factors or metabolic changes other than diabetes rather than as biomarkers of diabetes or insulin resistance.


Psychodynamic psychotherapy is frequently applied in the treatment of social phobia. Nevertheless, there has been a lack of studies on the transfer of manualized treatments to routine psychodynamic practice. Our study is the first one to examine the effects of additional training in a manualized Short Term Psychodynamic Psychotherapy (STPP) procedure on outcome in routine psychotherapy for social phobia. This study is an extension to a large multi-site RCT (N = 512) comparing the efficacy of STPP to Cognitive-Behavioral Therapy (CBT) of Social Phobia.The manualized treatment is designed for a time limited approach with 25 individual sessions of STPP over 6 months. Private practitioners will be randomized to training in manualized STPP vs. treatment as usual without a specific training (control condition). We plan to enrol a total of 105 patients (84 completers). Assessments will be conducted before treatment starts, after 8 and 15 weeks, after 25 treatment sessions, at the end of treatment, 6 months and 12 months after termination of treatment. The primary outcome measure is the Liebowitz Social Anxiety Scale. Remission from social phobia is defined scoring with 30 or less points on this scale.We will investigate how the treatment can be transferred from a controlled trial into the less structured setting of routine clinical care. This question represents Phase IV of psychotherapy research. It combines the benefits of randomized controlled and naturalistic research. The study is genuinely designed to promote faster and more widespread dissemination of effective interventions. It will answer the questions whether manualized STPP can be implemented into routine outpatient care, whether the new methods improve treatment courses and outcomes and whether treatment effects reached in routine psychotherapeutic treatments are comparable to those of the controlled, strictly manualized treatment of the main study.German Clinical Trials Register (DRKS) DRKS00000570 Social phobia  is a disorder marked by an irrational intense fear of social or performance situations in which embarrassment may occur. According to the DSM-IV  diagnostThe average 12 months prevalence rate of social phobia in the German population is 2% . Women aThe quality and effectiveness of psychodynamic psychotherapy in clinical practice, conducted by more than 50% of certified psychotherapists  in GermaThe study is being carried out at three trial sites. The participating centres are the Clinic for Psychosomatic Medicine and Psychotherapy of the University Medial Centre, Johannes Gutenberg University, Mainz, the Department of Psychosomatics and Psychotherapy, University of Giessen and the Department of Psychosomatic Medicine and Psychotherapy, Medical Faculty Carl Gustav Carus, Technical University of Dresden.In contrast to other RCTs in this trial patients are not recruited by centres. Participating therapist announce patients potentially fulfilling inclusion criteria and willing to participate to the trial site.For recruitment of therapists all officially listed  psychodynamic psychotherapists in the regions of the trial sites are asked for willingness to participate as study therapists. All therapists underwent a specific training (about 5 years of training) in psychodynamic psychotherapy. Due to the intended naturalistic character of our study we have defined relatively broad inclusion criteria for the participating therapists. Therapists can be of any age and gender. Double certification in CBT is not an exclusion criterion, as it is relatively rare in the German health care system. Therapists from the first funding period - specifically trained in STPP for Social Phobia are excluded.Therapeutic experience (including former training in SET) and allegiance to the treatment condition will be assessed.Patients' inclusion and exclusion criteria are listed in table The manualized treatment approach is based on Luborsky's Supportive Expressive Therapy (SET). The treatment includes the characteristic elements of SET therapy, that is, setting goals, focus on the Core Conflictual Relationship Theme (CCRT) associated with the patient's symptoms, interpretive interventions to enhance insight into the CCRT, and supportive interventions, in particular fostering a helping alliance. In order to tailor the treatment more specifically to social phobia, treatment elements have been added, for example informing the patient about the disorder and the treatment, a specific focus on shame and on unrealistic demands, and encouraging the patient to confront anxiety-provoking situations. More directive interventions are included as well, such as specific prescriptions to stop persisting self-devaluations . The treThose patients who are treated in the control condition will receive standard psychodynamic treatment.The time points of assessment are shown in Figure Patients are assessed by independent and trained SCID interviewers, who are blind to the treatment condition.The research questions of this trial are:(1) How can manualized STPP be implemented into routine outpatient care?(2) Will the new methods lead to an improvement of treatment courses and outcomes?(3) Will treatment effects reached in routine psychotherapeutic treatments be comparable to those of the controlled, strictly manualized treatment of the main study?The major hypotheses are: (1) Treatment effects reached by private practitioners trained with the manualized procedure of STPP of the main trial will be superior to therapists who apply their usual psychodynamic treatment. (2) Implementation of manualized STPP will lead to an average reduction of treatment duration and costs.Further objectives: a) direct comparison (using the same measures) of results based on an efficacy and an effectiveness design; b) comparison between effectiveness in different fields of health care delivery. In combination with the results of the RCT from the first funding period, this study will allow to estimate the reduction of treatment duration and costs made possible through implementation of treatment manuals derived from the main trial into clinical practice.Furthermore, this trial has been planned in close collaboration with the parallel trial for short-term cognitive-behavioural therapy (CBT). Endpoints and outcome measures were chosen in accordance with the main trial  to allowThe primary outcome measure is the Liebowitz Social Anxiety Scale (LSAS ) ≤30 indFurthermore, costs of treatment of Social Phobia are assessed with the German adaptation of the client sociodemographic and service receipt inventory (CSSRI ). This qBeing aware of the controversy whether RCT and efficacy studies reach the same effect sizes we used two recent meta-analyses on RCTs in STPP to estimate expected effect sizes. Abbass et al. (2006)  includedIn their meta-analysis, Leichsenring et al. (2004)  reportedα = z-value for probability of error type I alpha, zβ = z-value for probability of error type II beta, σ = standard deviation of outcome, E = expected ES of outcome, m = mean observations for each cluster, ρ = Intracluster correlation coefficient (ICC), ES = E/σ = standardized effect size), we introduced the following conservative assumptions:a) The ICC was set to 15%, which is high for comparable studies. According to Campbell (2001)  the ICC b) The average number of patients in a cluster was assumed to be 2. In fact, due to the prevalence of the disease we expect the average number of patients in a cluster to be less than 2.c) Within the planning the sample size of 42 per group was calculated for patients completing the trial. For the primary analysis (ITT) drop-outs will be analysed as patients without remission. When assuming less than 50% remitters and an equal drop-out rate in both treatment groups, the absolute difference between remission rates will not change, but the relative difference will be much greater and will enlarge the difference between treatments substantially.At a conservative drop-out rate of 25% (taking into account slightly elevated drop-outs in a practice study), a total of N = 105 patients are required to be allocated to the trial. Thus, N = 35 patients will have to be included in each centre. According to the data of the Davidson et al. (2004) ).The procedure set out in this protocol, pertaining to the conduct, evaluation, and documentation of this trial, were designed to ensure that all persons involved in the trial abide by Good Clinical Practice (GCP) and the ethical principles described in the current revision of the Declaration of Helsinki. The trial will be carried out in keeping with local legal and regulatory requirements.Before being admitted to the clinical trial, patients must consent to participate after the nature, scope, and possible consequences of the clinical trial have been explained in a form understandable to them. The patients must give written informed consent to participate in the study including their consent to publish.The study is designed as an extension to the larger multi-site project in which Cognitive-Behavioral Therapy (CBT) and Short Term Psychodynamic Psychotherapy (STPP) of Social Phobia based on SET have been evaluated . It combIn contrast to the previous RCT in this study the patients are not recruited by the participating centres. Patients will seek treatment in the regular way of the German health care system attending private practitioners. Therefore, participating therapists recruit patients and announce them to the study centres. In the previous RCT treatments were limited to 25 sessions. In our study therapists are completely free to determine treatment duration. Accordingly, we determined primary outcome after 25 sessions. Our comparison group is naturalistically treated with standard psychodynamic psychotherapy without any additional training of the therapists.Examinations of these issues in a methodologically rigorous manner will be of high relevance not only for the domain of social phobia but for the dissemination of innovative psychotherapeutic treatments in general.Implementing the best obtainable treatment into the practice of experienced psychotherapists can be expected to increase treatment effectiveness. While evidence for the efficacy of Supportive Expressive Psychotherapy (SET) and other variants of Short Term Psychodynamic Psychotherapy (STPP) has accumulated ,23, therADIS-IV: Diagnostic interview; AE: Adverse event; BDI: Beck Depression Inventory; BMBF: Federal Ministry of Education and Research; BSSS: Berlin Social Support Scale; CBT: Cognitive Behavioral Therapy; CCRT: Core Conflictual Relationship Theme; CSSRI: Client Sociodemographic and Service Receipt Inventory; CDS: Cambridge Depersonalization Scale; DKB: Dresdner Körperbildfragebogen; CRF: Case Report Form; DMSB: Data Monitoring and Safety Board; DSM: Diagnostic and Statistical Manual of Mental Disorders; EC: Ethic Committee; EQ-5D: Quality of life questionnaire; ES: Effect size; FSKN: Frankfurt self concept scales; HAQ: Helping Alliance Questionnaire; ICC: Intracluster Correlation Coefficient; ICD-10: International Classification of Diseases; ITT: Intention to treat; IZKS: Interdisciplinary Centre for Clinical Trials; LOCF: Last observation carried forward; LSAS: Liebowitz Social Anxiety Scale; MedDRA: Medical Dictionnary for Regulatory Activities; RCT: Randomised Controlled Trial; SAD: Social Anxiety Disorder; SAE: Serious Adverse Event; SCID: Structured Clinical Interview for DSM Disorders; SET: Supportive Expressive Therapy; SP: Social Phobia; SPAI: Social Phobia and Anxiety Inventory; SSRI: Selective serotonin reuptake inhibitors; STPP: Short Term Psychodynamic PsychotherapyThe authors declare that they have no competing interests.JW did the first draft of the manuscript. JW, FL and MEB did the final draft of the manuscript and critically revised it for its intellectual content. JW, CR, AH, MC, FL, PJ, KP and MEB substantially contributed to the conception and the design of the study. All authors read and approved the final manuscript.


Improving the health and health literacy of low-income families is a national public health priority in the United States. The federal Head Start program provides a national infrastructure for implementation of health promotion interventions for young children and their families. The Health Care Institute (HCI) at the Anderson School of Management at the University of California, Los Angeles, developed a structured approach to health promotion training for Head Start grantees using business management principles. This article describes the HCI approach and provides examples of implemented programs and selected outcomes, including knowledge and behavior changes among Head Start staff and families. This prevention-focused training platform has reached 60,000 Head Start families in the United States since its inception in 2001. HCI has demonstrated consistent outcomes in diverse settings and cultures, suggesting both scalability and sustainability. Compared with children from high-income families, children from low-income families in the United States face disproportionate health challenges and have worse reported child health status  and healHead Start (HS), a national early childhood program for low-income families in the United States, was created in 1964 as part of the War on Poverty. HS and Early Head Start (EHS) programs annually serve approximately 1 million children aged 0 to 5 years. Recognizing the important relationship between health and school readiness, HS has long required its grantees to coordinate health-related services such as basic screenings, health education, and referrals to health providers . Each grSince 1991, the Anderson School of Management at the University of California, Los Angeles (UCLA) has led annual leadership training for HS administrators. The UCLA/Johnson & Johnson Head Start Management Fellows Program has trained more than 1,400 HS leaders from grantee centers across the United States. On the basis of information provided via a 2001 survey of HS directors, the UCLA/Johnson & Johnson Health Care Institute (HCI) was formed to improve health literacy among HS families. The survey indicated that although grantees had access to health materials and resources to conduct health education trainings, these sessions were often poorly attended and the materials were not well understood . The HIP is based on the Business Improvement Project, a tool used in the Management Development for Entrepreneurs executive training program at the UCLA Anderson School of Management . The HIPAfter an initial planning meeting, leadership teams from as many as 50 HS grantees attend a 2-day train-the-trainer (TTT) event organized by HCI. Curriculum topics include strategic planning, project management, parent and staff motivation, marketing, and community relations. Teams use this time to refine their HIPs. A mock parent training demonstration during the TTT allows staff attendees to “walk in their families’ shoes” and learn the importance of audience engagement and interaction. In addition to the presentation of health education materials, the trainings include hands-on activities using topic-relevant tools  and incentives such as door prizes. After the TTT, HS leadership teams return home to implement training events, customized to meet the needs of local communities, for staff and parents at their grantee sites.The leadership teams train their entire HS staff using topic-specific health promotion materials provided by UCLA. HCI staff, faculty, and field-based partners provide technical assistance and advice throughout the implementation process. The staff training provides a model for the staff on how to lead interactive and engaging sessions for parents and children. Following the staff trainings, grantees engage their local communities, applying newly learned marketing strategies to engage local businesses, services, and health professionals and to secure in-kind donations and media coverage for the parent training event. At this point, grantees adapt their implementation strategies to meet local needs, translating materials into appropriate languages, incorporating cultural food preferences, and adding creative features to the event. The outreach process helps to build anticipation for the event and promote high attendance rates.A key goal of logistics planning is reducing barriers to attendance by providing transportation, child care, and a complimentary healthful meal and holding trainings during hours that maximize parent availability (including weekends and evenings). Health materials developed by HCI are written at a low literacy level, using graphics and limited text, and generally include slides for trainers and books and handouts for parents to take home. The training blends many educational techniques: audio, visual, hands-on, group with peer-to-peer teaching, and handouts for home use. The event also provides the opportunity for social interaction and networking among parents.Following the parents’ training, typically 3 home visits or workshops by HS staff are dedicated to reinforcement of the concepts learned at the initial training. These reinforcement activities help maintain family and staff engagement and focus on family assets that facilitate positive health behavior changes. Classroom teachers are encouraged to incorporate the health topics into daily classroom activities and curricula. Again, grantees have flexibility in designing the reinforcement activities that best meet local needs and cultures and use existing HS infrastructure, aligning activities with HS program performance standards.At the conclusion of the reinforcement period, usually 3 to 4 months after the initial training, a graduation event celebrates families’ participation. This event is a forum for sharing success stories and building relationships. Certificates of completion enhance parents’ sense of accomplishment in building skills to care for their families.For each implemented health promotion module HCI has collected preintervention and postintervention data from HS staff and parents. The baseline staff and parent measurements are generally done at the staff and parent training sessions and include written questionnaires to measure topic-specific health knowledge and self-reported behaviors. The same questionnaire is given again at the graduation session to measure changes in knowledge and behaviors. If literacy limitations pose problems for families to complete these written questionnaires independently, they are administered orally by staff.Once HS grantees participate in the initial TTT, they can implement other health promotion modules using a similar approach with new topic-specific materials introduced during webinars by HCI. From 2001 to 2012, we trained 240 HS grantees in 43 states to implement health promotion interventions on management of common childhood illnesses, oral health, and obesity prevention, reaching a total of 60,000 HS families. HCI materials have been translated into 7 languages and adapted for 10 ethnicities. Additional modules, such as use of over-the-counter medicines, home safety, vaccines, prenatal care, sun safety and secondhand smoke avoidance, are in various stages of development and testing .The first topic HCI addressed in 2001 was management of common childhood illnesses, designed to help parents treat common symptoms at home and learn practical skills such as how to use a thermometer and measure over-the-counter medicines. Parents also learned how to use a simple health reference book and when to consult a health care provider. Comparison of data from pre- and postintervention parent questionnaires showed a significant decrease in reported number of missed school and work days and significant decreases in reported numbers of emergency department and doctor visits . HCI theP < .001) and adults  over 6 months. We also documented increased nutrition knowledge, positive nutrition-related behavior changes, and increased frequency of physical activity  among parents, staff, and children, and a decrease in the proportion of obese children , suggesting that simply distributing written information is likely ineffective. A few grantees started the planning and training process but never completed implementation — these grantees tended to have directors who were not invested , underscoring the importance of the grantee leadership teams as organizational drivers in the diffusion of new programs. Finally, barriers to parent participation are generally practical ones, such as lack of time, transportation, or child care, but may also include social factors, such as mistrust of staff because of prior negative experiences or perceived exclusion because of linguistic or cultural differences. Our training process encourages staff to recognize and address these barriers and to approach all families with the utmost respect, building on the trusting relationships usually established during the HS enrollment process.HCI has applied a management training approach to health promotion implementation, using systematic strategies for planning, training, and engaging staff and families through a social-ecological framework. The HCI health promotion training model described in this article is a promising approach that has been replicated widely and disseminated across many HS sites, many of these implementing programs year after year. After attending just one TTT event, grantees are able to repeat the program and apply the same approach to multiple health topics. The HCI experience highlights the value of a systematic approach to dissemination of health promotion, consistent with dissemination frameworks for evidence-based health promotion practices reported previously . This apThe studies conducted by HCI to date are limited by lack of comparison groups, making the changes seen from pre- to postintervention measurement subject to selection bias. Future studies should measure the effectiveness of the HCI approach more rigorously using an experimental or quasiexperimental study design and also measure outcomes beyond the 6-month intervention period. Also, we have focused on measuring knowledge and behavior changes among families and staff but have limited implementation data. A more precise understanding of which program components are most important would be useful, as well as which organizational-level factors influence individual-level outcomes.Another potential disadvantage of the HCI approach is that it is initially time-intensive, requiring multiple training sessions and reinforcement activities. We have found, however, that this investment of time and energy yields important intangible dividends, such as leadership capital and parent engagement. We believe this approach is essential to engage staff and families consistently and to promote positive behavior changes, and have found that efficiency increases with grantee expertise. Now, in partnership with the American Academy of Pediatrics as part of the Head Start National Center on Health, the HCI model is poised for wider dissemination in HS as well as across other early childhood programs nationwide.