Cellular localization, assembly and abnormal aggregation of neurofilaments depend on phosphorylation. Pathological processes associated with neurodegeneration exhibit aberrant accumulation of microtubule associated aggregated forms of hyperphosphorylated neuronal protein tau in cell bodies. These processes are critical for the disease progression in patients suffering from Alzheimer’s disease, Parkinson’s disease, and Amyotrophic Lateral Sclerosis. In healthy cells, tau is localized in axons. Topographic regulation suggests that whereas the sites of synthesis of kinases and neurofilaments are the cell bodies, and sites of their functional assemblies are axons, phosphorylation/dephosphorylation are the key processes that arrange the molecules at their precise locations. Phosphorylation sites in the dynamic developmental and degenerative processes differ. Not all these processes are well understood. New advancements identify epigenetic factors involved in AD which account for the influence of age-related environment/genome interactions leading to the disease. Progress in proteomics highlights previously found major proteins and adds more to the list of those involved in AD. New key elements of specificity provide determinants of molecular recognition important for the assembly of macromolecular complexes. In this review, we discuss aberrant spatial distribution of neuronal polypeptides observed in neuropathies: aggregation, association with proteins of the neuronal cytoskeleton, and phosphorylation dependent dynamics. Particularly, we emphasize recent advancements in understanding the function and determinants of specific association of molecules involved in Alzheimer’s disease with respect to the topographic regulation of phosphorylation in neuronal cytoskeleton and implications for the design of new therapies. Further, we address the role of various filament systems in maintenance of the shape, rigidity and dynamics of the cytoskeleton. StructuFigure 1) and are candidates for binding other ligands. Carrying PxxP sequence, tau mono-, di- and tri-phosphorylated peptides exhibit polyproline II conformation in complex with antibody  and PIN1 . Interactions of two Pin1 domains, WW substrate recognition and catalytic , with each other, PP2A and other proteins contribute to its function . All six human tau isoforms show common mechanism of tau/PAD  conformational mobility associated with axonal transport inhibition  which are tethered to a membrane. Ankyrin repeats target proteins to the plasma membrane and link membrane proteins to the actin/spectrin cytoskeleton .Studies of neuron specific cytoskeletal proteins such as tau and light (NFL), medium (NFM), and heavy (NFH) subunits of NFs show that phosphorylation plays important role in their function and dynamics. Phosphorylation stabilizes NFs, protects from proteolysis, and promotes calcium mediated assembly of NF subunits and cytoskeletal components in axons, whereas dephosphorylation results in more dynamic chains which repair and regenerate less mobile chains . Tau regfunction . Tau obthibition . Both NFNeuron-specific cytoskeleton gives neuronal cell its shape. Unique features of the neuron with cell body in the central and meters long axons in the peripheral nervous system require specific structural components and maintenance . The asyPathological hyperphosphorylated and aggregated tau is surrounded by more than 150 proteins as shown by studies of neurofibrillary tangles . Many efHyperphosphorylation with involvement of Cdk5, GSK3β and other kinases and oxidation contribute to AD pathogenesis . PhosphoFigure 2) as one of the key risk factors for AD , ankyrin B (ANK2/ANKB), and ankyrin G (ANK3/ANKG), all of which have similar structure and function, and undergo alternative splicing to generate multiple isoforms . Epigenes for AD . ANK1 iss for AD . Microgls for AD  shows ho+ and K+ channels and their interactions with numerous modulators  makes connections to membrane proteins associated with lipid rafts (Progress in proteomics reveals AnkB and AnkG involvement in AD . Giant ldulators . AnkG, sid rafts . AnkG maid rafts  and an iid rafts .Progress in understanding the role of phosphorylation/dephosphorylation in regulation of spatial distribution and transport of proteins involved in neurodegenerative diseases brings new approaches and evolvement of new treatments. Understanding MT dynamics, posttranslational modifications, specific distribution and assembly of cellular components, and signaling which links neuronal dysfunction to neuropathies leads to the development of new therapies . Aβ accuAll authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The Church Health Association of Kenya (CHAK) partnered with health facilities managed by faith-based organizations (FBOs), religious leaders, and community health volunteers to increase access to family planning in western Kenya. FBO-managed health facilities saw large increases in family planning uptake over the 5-year project, particularly for implants. The Church Health Association of Kenya (CHAK) partnered with health facilities managed by faith-based organizations (FBOs), religious leaders, and community health volunteers to increase access to family planning in western Kenya. FBO-managed health facilities saw large increases in family planning uptake over the 5-year project, particularly for implants. Health facilities managed by faith-based organizations (FBOs) are important providers of health care in Kenya but provide only a small proportion of family planning services in the country. From 2013 to 2017, the Christian Health Association of Kenya (CHAK) implemented a project with 6 FBO-managed health facilities to increase voluntary family planning services in western Kenya, in partnership with religious leaders and community health volunteers (CHVs). The project aimed to build capacity of FBO-managed health facilities, increase religious leaders' knowledge of family planning, mobilize communities, improve family planning access and referrals for services, and advocate for improved family planning commodity security from the public sector. Project impact was evaluated using facility-level service statistics, project records and reports, and feedback from religious leaders and CHVs who implemented the project. Facility service statistics showed large increases in family planning visits. Phase 1 (2013–2014) was implemented at 2 health facilities, where client visits for family planning increased sixfold  with tenfold increases seen in client visits for pills, intrauterine devices, and implants. In Phase 2 (2015–2017), the project was expanded to an additional 4 health facilities and total client visits for family planning nearly doubled . During Phase 2, new client visits for implants increased threefold, making implants the most popular family planning method. Religious leaders who implemented the project reported reaching nearly 700,000 people with family planning messages and referring more than 87,000 clients to health facilities for family planning services. The religious leaders expressed confidence in the effectiveness of the project and in their role in enhancing access to voluntary family planning. Health facilities, religious leaders, and CHVs also reported multiple challenges to implementation, including inconsistent supply of family planning commodities from county health departments. This project demonstrates the potential of FBO-managed facilities and faith leaders to increase family planning demand and service provision, as well as the importance of coordination with the public sector to ensure supply of commodities and support for FBO-managed facilities. Faith-based organizations (FBOs) are important providers of health care in many sub-Saharan African countries,,–,FBOs in Africa are trusted by communities and thus well-placed to promote and provide family planning services,This article presents an initiative of the Christian Health Association of Kenya (CHAK) to partner with FBO-managed health facilities and religious leaders to increase family planning access in the Nyanza and Western regions of Kenya. CHAK is a national FBO, founded in 1946, which comprises 24 hospitals, 57 health centers, 387 dispensaries, and 27 community-based health care programs owned by Protestant churches. These facilities and programs work in partnership with the Kenya Ministry of Health (MOH), county health departments, NGOs, development partners, the private health sector, and communities. CHAK has a central mandate of engaging religious leaders to improve health and a long-standing focus on family planning, including implementation of a World Bank-funded project in 2010 that trained pastors to educate parishioners about the value of family planning from the pulpit.Nationally, Kenya's total fertility rate has declined from 4.9 births per woman in 2003 to 3.9 in 2014.The project was implemented in Kakamega, Siaya, and Vihiga counties, which are contiguous counties in the Nyanza and Western regions of Kenya near Lake Victoria and the border with Uganda. These counties have a higher total fertility rate than the national average . Four ofCHAK targeted 3 counties based on their high total fertility rate and unmet family planning need.The ongoing project has a mandate to (1) build capacity of FBO-managed health facilities and community-based providers of family planning services, (2) sensitize Protestant, Catholic, and Muslim religious leaders, (3) mobilize communities, (4) improve family planning access and referrals from communities to health facilities, and (5) advocate for improved commodity security from MOH and county health departments. A particular goal of the project is to train and engage religious leaders to provide family planning information and referrals as part of their commitment to the health and well-being of families in their communities. Key project activities are highlighted in Phase 1 of the project was initiated in 2013 in 2 CHAK health facilities and their surrounding communities: Dophil Maternity and Nursing Home and Namasoli Health Center , religious leaders, and CHVs. CHAK was able to identify challenges and bottlenecks to family planning access and develop a roadmap and implementation plan that defined desired outcomes and steps to achieving those outcomes.Religious leaders and CHVs were tasked with implementing the project at the community level. They received project-branded hats and t-shirts to help identify them in their role as community educators, but they were unpaid. Religious leaders received a 3-day training focused on information about family planning, communication skills, and counseling skills. CHVs had already been trained by MOH but were not engaged in community-based distribution of family planning commodities prior to the project. They received a further 5-day training to equip them to counsel family planning clients and assist them in making informed family planning choices, distribute certain family planning commodities according to MOH guidelines , and refer clients desiring other family planning methods to health facilities. Each CHV received a branded bag stocked with family planning commodities  and a penis model to use in demonstrating male condom use. CHVs were also given funds for transport to allow them to fulfill their responsibilities.Religious leaders and CHVs worked together to lead community dialogues about family planning. Before each dialogue, the leaders met to talk about family planning methods and address any questions or concerns about family planning (particularly among religious leaders). Religious leaders also invited CHVs to talk about family planning in forums such as church women's groups and youth groups. This approach has been so successful that CHAK has initiated additional projects to train religious leaders to educate their communities about hypertension and diabetes and to enlist their help in tuberculosis case finding.Religious leaders and CHVs worked together to lead community dialogues about family planning.Throughout Phases 1 and 2, CHAK held biannual stakeholder meetings with faith leaders, community gate keepers such as chiefs and community administrators, health workers, facility managers, CHAK managers, county officials, and county Ministry of Health staff. This engagement with stakeholders was crucial to garner support, avoid duplication of efforts, and ensure successful project outcomes. County health departments provided training materials, reporting tools and registers, and family planning commodities. Throughout project implementation, CHAK worked with county governments to ensure that the facilities received adequate supplies of family planning commodities. CHAK also supported facilities through offering on-the-job training for health workers (particularly training on long-acting family planning methods), supportive supervision, and mentoring.CHAK received approval for the project from health facility administrators, health providers, community religious leaders, and religious leaders governing the health facilities. Health facilities approved use of facility-level data  in evaluating the project. MOH and county health departments also approved and supported the project because it served to improve county family planning performance.Funding for the project was provided by the David and Lucile Packard Foundation under the Africa Christian Health Associations Platform Family Planning Project in 2 separate grants, which accounts for the 2 phases of the project. Christian Connections for International Health (CCIH) collaborated closely with CHAK in the conceptualization, proposal development, and early implementation of the project, including baseline assessments at the health facilities. CCIH is an association of FBOs and individuals working in international health that has been a leader in advocating for family planning funding and promoting FBO involvement in family planning.In order to evaluate the impact of this project, we assessed multiple sources of data, including facility service statistics, project records and reports, and feedback from religious leaders and CHVs who implemented the project.For Phase 1 (2013–2014), 2 of the authors (JK and DH) collected service statistics on new and return visits according to family planning method from the registers of Dophil Maternity and Nursing Home and Namasoli Health Center for 2012 (baseline prior to project implementation), 2013 (after project implementation), and 2014. All data collected from these health facilities were part of the standard MOH reporting system for counties, contained no identifying patient information, and provided a comparable and consistent data source before and during the project. In Phase 2 (2015–2017), the project added 4 additional health facilities . BaselinThroughout Phases 1 and 2, CHVs submitted monthly reports of how many clients they had provided with pills, condoms, and CycleBeads in households and communities. These clients were included in health facility data. In 2014, an unanticipated innovation led to another source of data with which to evaluate the pilot project. As well as providing family planning messages to their congregations and communities, religious leaders began making family planning referrals directly to CHVs and health facilities, an activity that had not been part of the original project design. The project thus asked religious leaders to begin reporting monthly, using a standardized form, the number of community members they had reached with family planning messages and the number of clients they had referred to health facilities and CHVs. Religious leaders and CHVs were provided with mobile phone-based reporting tools, but not all of them had phones or Internet access to support the technology; consequently, some chose to instead submit reports in hard copy. CHVs and religious leaders also submitted written feedback on the project as part of their monthly reports. The CHAK program coordinator (JK) made regular supervisory visits to the facilities to monitor the project and maintain an ongoing dialogue with religious leaders, CHVs, clinical staff, and the communities.In Phase 1 (2013–2014), 30 religious leaders and 60 CHVs were trained with updated family planning information, counseling, and referral skills. According to monthly reports submitted by religious leaders during Phase 1, they reached 5,154 clients in the Dophil catchment area and 7,198 clients in the Namasoli catchment area with family planning messages, and referred 450 and 988 clients to the 2 facilities, respectively. In Phase 2 (2015–2017), an additional 32 religious leaders and 52 CHVs were trained. By 2017, religious leaders had reached a total of 675,000 men and women with family planning information and had referred 85,810 clients to health facilities for family planning services.By 2017, religious leaders had reached 675,000 people with family planning information and had referred 85,810 for family planning services.Religious leaders and CHVs reported satisfaction with the project and confidence that it was benefiting the health and well-being of families in their communities. Religious leaders reported that they were comfortable in and enthusiastic about their role in providing education about family planning and referrals for family planning services. CHVs reported that community-based distribution reduced barriers to women accessing family planning services, and that working with religious leaders facilitated acceptance of their work by communities. During Phase 1, Dophil and Namasoli saw large increases in family planning visits compared with the 2012 baseline . Total cIn Phase 2, total client visits to the 6 health facilities for family planning nearly doubled, from 7,925 visits (2015) to 11,183 visits (2016) to 14,832 visits (2017). Data from Phase 2 also distinguished between new visits (which represent unique clients) and revisits . New cliIn Phase 2, total client visits to the 6 health facilities for family planning nearly doubled.According to health center staff, some returning visits were scheduled follow-up visits and others were initiated by clients who had experienced side effects, had questions, or had other needs for ongoing care. Injectables are effective for 3 months, meaning women using injectables should have returned 4 times per year. However, the number of revisits for injectables in 2016 and 2017 (the second and third years of Phase 2) suggests that not all new users of injectables were returning to the same facilities 4 times the following year. Revisits for injectables in 2016 and 2017 were only 2 to 3 times the number of new visits for injectables the previous year, consistent with typical discontinuation rates for injectables. This finding suggests that some women discontinued injectable contraceptives, while others may have obtained injections at facilities not included in this study. Similarly, data for pill revisits suggest that some women discontinued pill usage. Clients were typically given a 3-cycle supply of pills at each visit, but sometimes only 1 or 2 cycles of pills were provided if supplies were short, which may have contributed to some women discontinuing usage.The number of revisits for IUDs was smaller than for pills and injectables, as expected. Women receiving IUDs were scheduled for 1-month and 3-month follow-up visits. The copper-bearing CuT 380A, which is effective for up to 12 years, was the most common IUD provided. Implants were primarily 3-year devices (Implanon or Nexplanon) and less commonly 5-year devices (Jadelle), and women receiving implants were scheduled for a 1-month follow-up visit after insertion. The number of revisits among women using implants was relatively high, compared with revisits among women using IUDs. Condoms were distributed in variable numbers, depending on available stock and client request, but the fact that a majority of visits for condoms were new visits (rather than revisits) suggests that women were not regularly obtaining condoms from these facilities as a primary means of contraception.As shown in Considerable variation existed between facilities in total client visits for family planning and in the popularity of various methods.Whereas health facility data indicate that the project was highly successful in increasing family planning access, CHAK also noted a number of challenges to implementation faced by religious leaders, CHVs, and health facilities. These challenges are described in The rapid and sustained increase in family planning uptake by the 6 participating health facilities over the course of project implementation indicates that FBOs can substantially expand services to help address unmet need for family planning in Kenya. Data on facility visits, as assessed in this study, have been found to be a fairly accurate proxy for trends in contraceptive prevalence.Implants were the most frequently requested family planning method and had the largest increase in demand. This high demand for implants is consistent with analysis showing that large increases in implant use across sub-Saharan Africa since the early 2000s are driving increased modern contraceptive use in the region.This project demonstrates that religious leaders can effectively reach large numbers of people in their communities and congregations with family planning messages, reinforcing previous findings that people have a high degree of trust in FBOs and religious leaders and that religious leaders are thus well placed to address the unmet need for family planning.This project demonstrates that religious leaders can effectively reach large numbers of people with family planning messages.CHVs were instrumental in bridging the gap between communities and health facilities. Their effectiveness depended on appropriation training, provision of family planning commodities, and motivation from health facility staff and their religious leaders. Monthly meetings between CHVs and health facility staff provided an opportunity for updates, problem solving, and commodity supply. At times CHVs also participated in church services to provide health and family planning messages.County officials were also an integral part of the project, participating in launch and training workshops as well as providing commodities. In some cases, county officials also allowed staff who were paid by the MOH to be seconded to FBO facilities. Project results were included in county reporting, and county officials thus viewed the performance of FBO projects and facilities as part of county efforts to strengthen services. CHAK is now expanding this model of collaboration between FBO-managed health facilities and counties to other regions of the country. The challenges faced by health facilities in procuring family planning commodities from county health departments demonstrate the need for continuing coordination with the public sector, especially given the reality of constrained government resources for family planning and inconsistent supply of commodities. Continued advocacy, engagement, and good relationships with county officials are necessary to support staffing of health facilities and training of staff, as well as procurement of materials and commodities.Procuring family planning commodities was a recurring challenge for this project and is a common problem across Africa, especially for FBO-managed facilities.Procuring family planning commodities was a recurring challenge and is a common problem across Africa, especially for FBO-managed facilities.Besides the challenges described, we also note several limitations in the available data and interpretation of those data. Because the project had no control group, we cannot know to what degree factors external to the project and project facilities affected family planning uptake at those facilities. Stock-outs of family planning commodities at other facilities may have increased demand for family planning at the project facilities, and the health worker strikes during Phase 2 of the project may have had the same effect. Furthermore, no baseline data are available for the 4 facilities added in Phase 2, meaning that while data from 2015 to 2017 show an increase in family planning visits beginning in the first year of Phase 2, they cannot answer how family planning uptake changed from pre-implementation to the first year of Phase 2 implementation. The increase in family planning uptake for 2015–2017 likely underestimates the impact of the project in Phase 2.We offer the following recommendations for similar programs attempting to engage religious leaders and FBO-managed facilities for rapid and sustainable increases in voluntary family planning. In addition, CHAK is willing to share expertise and any tools developed for the project, including training materials and reporting forms, and would welcome visits to the health facilities that implemented the project.The project should ensure that religious leaders are appropriately invited and adequately trained to participate in the project, and it should include religious leaders of all faith traditions if possible. Adequate training includes up-to-date information on methods of family planning and addressing common misconceptions held by the community and religious leaders themselves. In this project, health facility staff issued invitations to Christian and Muslim leaders, which were well received. Also critical was giving religious leaders time to understand the training they received on family planning, ask questions, and discuss their new knowledge as well as their role in the project with their congregations. This collaborative process of “internal advocacy” was crucial to religious leaders (who are mostly men) having the support of their faith communities in taking on the role of family planning advocate.As noted, stakeholder engagement meetings were critical to ensure that government officials, faith leaders, health facilities, and other key stakeholders concurred with the project's goals and put their support behind the project in practical ways. The project also found other ways to increase stakeholder investment in the project. Providing CHVs and religious leaders with branded bags, t-shirts, and hats built morale and gave them a sense of ownership and commitment to the project. Communicating with CHVs, religious leaders, and health facilities about the project's progress at regular meetings, and sharing data from all health facilities with them, helped them to see the “big picture” of project impact and increased their investment in the project's success. These meetings also gave stakeholders an opportunity to discuss how the project might improve.A carefully designed monitoring and evaluation strategy is crucial for documenting progress toward project goals and should be implemented from the beginning of the project. Effective data management can be challenging in an environment in which electricity and telecommunications can be erratic. This project found that CHVs and religious leaders were often unable to use electronic reporting tools designed for mobile phones (via Internet or SMS) because they lacked funds to purchase data for their phones and also required training in use of these electronic tools. The project did not have funds for such training or to purchase mobile phone data for religious leaders and CHVs, so religious leaders and CHVs submitted paper reports to health facilities. Projects should be careful to design a monitoring and evaluation system that is realistic in the project environment.We believe this project provides an effective, scalable, and sustainable model for engaging with FBO-managed facilities, CHVs, and religious leaders to increase family planning demand and services in sub-Saharan Africa. These 3 partners formed a vital triangle of effective service provision, and the linkages between them enhanced performance and results. This study makes a particular contribution in identifying lessons learned for mobilizing religious leaders as effective promoters of voluntary family planning and facilitating access to services through referrals. Even given recent increases in family planning usage within sub-Saharan Africa, considerable unmet need remains. Greater support for the extensive service delivery infrastructure provided by FBOs, and effective engagement of religious leaders, can make a significant impact on addressing the unmet need for family planning in Africa.


Social and behavior change communication interventions are integral to improving dietary and care practices, but evidence on the impact of the combination and intensity of these interventions in different contexts is scarce.We examined the extent of and factors associated with intervention exposure: interpersonal communication (IPC) alone or with other interventions , number of and factors associated with IPC contacts, and combinations of intervention components and number of contacts associated with infant and young child feeding (IYCF) practices.n = 1001, 1720, and 1001 mothers with children aged <2 y, respectively). Multivariable regression models were used for analyses.We used endline survey data from impact evaluations in Bangladesh, Ethiopia, and Vietnam , minimum dietary diversity (OR: 1.8), and consumption of iron-rich foods (OR: 4.7). In Vietnam, exposure to IPC alone or with mass media was associated with higher odds of exclusive breastfeeding . Near-monthly visits were associated with 2–3 times higher odds of IYCF practices in Bangladesh and Ethiopia. In Vietnam, even 1 IPC visit was associated with 2 times higher odds of EBF.www.clinicaltrials.gov as NCT01678716 (Bangladesh), NCT02775552 (Ethiopia), and NCT01676623 (Vietnam).Exposure matters for impact, but the combination of behavior change interventions and number of IPC contacts required to support IYCF behavior change are context specific. This trial was registered at  Social and behavior change communication (SBCC) is an integral component of nutrition programs aiming to improve dietary and care practices. Interpersonal communication or counseling has been shown to be an effective behavior change intervention for improving breastfeeding and complementary feeding practices . The desTo guide the design, implementation, and scaling up of programs for breastfeeding counseling, the WHO recently developed a guideline on global, evidence-informed recommendations on breastfeeding counseling . The guiEvidence on the impact of counseling intensity is mixed, but many studies suggest that more intensive programs and counseling   and indiAlive & Thrive is an initiative that aims to improve infant and young child feeding (IYCF) practices through large-scale SBCC programs, which include interpersonal communication (IPC) delivered by frontline health workers . IPC dur1) the extent of exposure to the large-scale behavior change interventions in the 3 countries and the household, maternal, and child factors associated with intervention exposure; 2) the number of IPC contacts achieved and the factors associated with the number of contacts; and 3) the association between different combinations of interventions and number of contacts and IYCF practice outcomes.In this article, we examined the coverage and frequency of IPC with or without other SBCC interventions  across the 3 diverse country settings. Our objectives were to understand the following: This study used data from the impact evaluation of Alive & Thrive's intervention programs to improve IYCF practices in Bangladesh, Ethiopia, and Vietnam . In BangIn Bangladesh, BRAC, a large nongovernmental organization, delivered IPC and CM activities in 50 rural subdistricts through its existing countrywide essential health care program. In the intervention areas, BRAC health workers and community volunteers conducted multiple, age-targeted, IYCF-focused counseling visits to households with pregnant women and mothers of children ≤2 y of age . IYCF promotors were also recruited and trained to support them. CM included sensitization of community leaders about IYCF, and community theater shows focused on IYCF. The MM component consisted of the national broadcast of 7 television spots with messages on various aspects of IYCF—2 spots focused on breastfeeding, 4 spots focused on complementary feeding, and 1 spot focused on hygiene. In intervention areas that had low electricity and limited access to television, media-dark strategies such as local video screenings were carried out.woredas (districts) in northwest Amhara. In intervention areas, HEWs provided age-appropriate IYCF messaging to women from their last trimester of pregnancy to 2 y of child age  during health post  and home visits and conducted food demonstrations; HDTLs also provided the age-appropriate IYCF messaging during home visits, and agricultural extension workers promoted AG activities, such as designating a chicken whose eggs are prioritized for young children in the household and designating vegetables from homestead gardens to be prioritized for children. Priests and religious leaders delivered CM activities such as sermons about adequate child feeding during religious fasting periods, which are common and extensive in the region; and enhanced community conversations about IYCF were led by community-based organizations. The MM component consisted of a regional broadcast of a radio drama, which included 12 episodes with stories that aligned with Alive & Thrive's IYCF messages, associated jingles, and testimonials of model mothers. In intervention areas with limited access to radio, there were media-dark strategies such as broadcasting the radio drama through mobile vans with speakers and traveling performers to enact parts of the drama.In Ethiopia, Alive & Thrive with Save the Children worked with government health extension workers (HEWs), health development team leaders , and agricultural extension workers to deliver intensified IPC about IYCF and promote AG activities to benefit children <2 y of age in 10 In Vietnam, Alive & Thrive with Save the Children worked with the government to establish a total of 781 social franchises within government health facilities at the province, district, and commune levels in 15 of the 63 provinces to deliver high-quality IYCF counseling. Facilities were required to meet minimum criteria, including a standardized room dedicated to counseling, trained health staff (nurse midwives and doctors), and availability of job aids and client materials. The IPC schedule included 9–15 counseling contacts (≤8 breastfeeding contacts before 6 mo of age and 7 complementary feeding contacts between 6 and 24 mo) to each mother–child pair from the last trimester of pregnancy through the child's first 2 y of life. There was little to no CM, involving only the distribution of invitation cards to social franchises by village health workers to encourage mothers to attend counseling services. MM consisted of a nationally broadcast campaign that used television, print, and digital media; 2 television spots focused on breastfeeding, 1 spot focused on complementary feeding, and 1 spot promoted the use of franchise services. Other MM activities in intervention areas included community airing of loudspeaker announcements, posters promoting breastfeeding in commune health centers, billboards, and bus wraps.1) intervention areas that received intensified IPC, CM, and MM (and AG activities in Ethiopia only); and 2) comparison areas that received standard IPC and less-intensive CM and MM . Household data were collected through 2 cross-sectional surveys in the same communities, in 2010 and exactly 4 y later in 2014 (for Bangladesh and Vietnam), and in 2015 and exactly 2 y later in 2017 (for Ethiopia). Given the focus of this article on exposure to interventions, we used the endline survey data for the intervention samples only. The sample sizes included 1001 mothers with children <2 y of age in Bangladesh, 1760 mothers with children in Ethiopia (400 mothers with children aged 0–5.9 mo and 1360 mothers with children aged 6–23.9 mo), and 1001 mothers with children aged <2 y in Vietnam. Data were collected via face-to-face interviews using structured questionnaires. Informed consent was obtained from all mothers prior to their participation in the survey. Ethical approval was obtained from the institutional review boards of the Medical Research Council in Bangladesh, Addis Continental Institute of Public Health in Ethiopia, Union of Science and Technology Association in Vietnam, and the International Food Policy Research Institute in the United States. This trial was registered at www.clinicaltrials.gov as NCT01678716 (Bangladesh), NCT02775552 (Ethiopia), and NCT01676623 (Vietnam).The impact evaluations in all 3 countries used cluster-randomized designs. There were 2 program arms: 1) any AG, CM, or MM (no IPC); 2) IPC alone; 3) IPC and any AG, CM, or MM; and 4) no IPC, AG, CM, or MM.Exposure variables were based on self-reported exposure to IPC, AG, CM, and/or MM. For exposure to IPC, mothers were asked if they had been visited by a health or community worker in the last 6 mo (Bangladesh and Vietnam) or in the last 3 mo (Ethiopia) and received IYCF information. In Ethiopia only, mothers were also asked whether they heard about raising a baby's chicken or growing a baby's garden, which are AG activities with complementary feeding–related messages promoted by agricultural extension workers. For exposure to CM (in Bangladesh and Ethiopia), mothers were asked about whether they attended any of the activities related to IYCF—local theater, mobile television show, food demonstration, community conversation, and priest sermons. Exposure to MM considered ever-exposure to television spots about IYCF (Bangladesh and Vietnam) and radio drama (Ethiopia). Respondents were categorized into 4 exposure groups: For frequency of IPC, mothers were asked about the number of times they had IPC contacts in the last 6 mo (Bangladesh and Vietnam) or in the last 3 mo (Ethiopia). The proportions of respondents were shown by the number of contacts or 3–4 categories of contacts, depending on the distribution of respondents by frequency.1) exclusive breastfeeding (EBF) to 6 mo, defined as the proportion of infants 0–5 mo of age who are fed exclusively with breast milk ; 2) minimum meal frequency, defined as the proportion of breastfed and nonbreastfed children 6–23 mo of age who receive solid, semisolid, or soft foods the minimum number of times or more ; 3) minimum dietary diversity, defined as the proportion of children 6–23 mo of age who receive foods from ≥4 food groups ; and 4) consumption of iron-rich or iron-fortified foods, defined as the proportion of children 6–23 mo of age who receive an iron-rich or iron-fortified food that is specially designed for infants and young children or that is fortified in the home .Descriptive analysis was used to examine the study sample characteristics, exposure to individual or combinations of intervention components , and frequency of IPC contacts. Multinomial logistic regression analyses were used to test the association between the various household, maternal, and child factors and exposure groups or categories of IPC contacts. Household variables such as the number of children <5 y of age, socioeconomic status (SES), and food insecurity; maternal variables such as age, years of schooling, and ≥4 antenatal care (ANC) visits ; and child variables such as sex, age, and illness symptoms in the last 2 wk were selected as factors that may influence intervention exposure or IYCF practice outcomes, based on a resources for care conceptual framework . MultivaSupplemental Figure 1.Across the 3 countries, the mean number of household members was ∼5, and the number of children <5 y of age within households was similar  . In BangPatterns of association between household, maternal, and child factors and intervention exposure differed across the 3 countries  without IPC than with IPC in Vietnam only. On average, mothers received 8 visits in the last 6 mo, 2 visits in the last 3 mo, and 1 visit in the last 6 mo in Bangladesh, Ethiopia, and Vietnam, respectively. Our study results reflect different contexts in the 3 countries as seen by the different patterns of factors associated with intervention exposure and number of IPC contacts. In Bangladesh, there were positive, nonsignificant associations between any intervention exposure and IYCF practices, but we observed significant associations with ≥4 contacts. In Ethiopia, exposure to IPC with other interventions was associated with higher odds of minimum meal frequency, minimum dietary diversity, and consumption of iron-rich foods. In Vietnam, exposure to IPC alone or with MM was associated with higher odds of EBF. Near-monthly or more frequent visits were associated with higher odds of IYCF practices in Bangladesh and Ethiopia. In Vietnam, even 1 IPC visit was associated with higher odds of EBF, but most mothers who had an IPC visit were also exposed to MM.In the intervention areas, large overlap of IPC with other intervention components  was observed in Bangladesh and Ethiopia, where IPC was mainly community based and delivered through home visits. The other interventions extended reach to the target population not covered by IPC, but mostly they overlapped with and likely played a role in reinforcing the IPC contacts. In Vietnam, IPC contacts were facility-based only, and therefore more mothers were exposed to MM than IPC. Overall, 77% of mothers were exposed to any MM and 44% of them were exposed to MM alone; thus, MM played an important role in extending the reach of behavior change communication or IYCF messages to mothers in Vietnam, which was also documented during the process evaluation .The expected frequency of IPC contacts according to intervention design was mostly achieved in Bangladesh and Ethiopia but fell short in Vietnam. By design, Bangladeshi mothers were expected to receive at least monthly contacts , Ethiopian mothers were to receive bimonthly contacts , and Vietnamese mothers were to receive 8 contacts before 6 mo of age and 7 contacts between 6 and 23 mo . In Bangladesh, extensive cadres of BRAC frontline workers, dedicated to delivering health- and nutrition-promotion activities through home visits, were able to deliver monthly or more frequent IPC contacts through home visits. In Ethiopia, where government HEWs and community health volunteers delivered IPC through health post or home visits, respectively, ∼2 contacts over the 3-mo recall period were reported by mothers. In Vietnam, however, <1 contact over a 6-mo recall period was reported by mothers. Facility-based IPC delivered through government health centers was not able to achieve the planned regimen, reflecting the added challenge of generating a demand for these services so that mothers will go to the health facilities and attend them, compared with services delivered directly to their homes. Other constraints to utilization of the facility-based interventions included the distance to facilities and the lack of perceived need (the perception of need for IYCF counseling was less recognized than it is for illness) . InasmucThe patterns of household, maternal, and child factors associated with exposure to different combinations of intervention components and number of IPC contacts reflect different contexts across the 3 countries. In Bangladesh, mothers with higher SES, reflecting more household resources, were more likely to be exposed to other intervention components (CM or MM), with or without IPC. Mothers who received ≥4 ANC visits, reflecting health service use, were more likely to be in any exposure group. Those with older children and children with low birth weight were more likely to be exposed to other interventions without IPC. There was a mix of positive and negative conditions associated with exposure groups in Bangladesh, as well as in Ethiopia, reflecting a complex interplay of demand-side factors on how community workers might target beneficiaries and how beneficiaries access or use SBCC interventions. In Ethiopia, those with higher food insecurity and older maternal age were more likely to be exposed to IPC with other interventions, which may be a result of community health workers targeting poorer or more vulnerable households. Mothers who received ≥4 ANC visits, reflecting health service–seeking behavior, were also more likely exposed to IPC with other interventions.In Vietnam, mothers with higher SES and higher schooling were more likely exposed to IPC and MM, reflecting associations with positive resources and maternal capacity. Older mothers were less likely to be exposed to MM, with or without IPC. Mothers who reported being a housewife were less likely to be exposed to IPC alone or IPC with MM, indicating that they did not use or used less often the facility-based IPC than mothers who reported being employed, which appears to run counter to the idea that housewives may have more time to access IPC services. Mothers with older children were more likely to be exposed to MM alone and less likely to be exposed to IPC alone. A closer examination of factors associated with one-time, repeated, or recommended use of the facility-based IPC services in Vietnam was presented in a separate article . OverallIn relation to the number of IPC contacts, older maternal age, older child age, and receipt of ≥4 ANC visits were associated with more IPC contacts in Bangladesh, while those with more household members were less likely to receive >6 visits. Since IPC in Bangladesh was entirely home based, these relationships may reflect a combination of factors related to service demand (service-seeking) and delivery challenge (with more people residing in the house). In Ethiopia, higher food insecurity and receipt of ≥4 ANC visits were associated with ≥3 IPC visits, either through health post or home visits. Older age and more schooling among mothers were associated with any number of IPC contacts. In both Ethiopia and Vietnam, being a housewife and older child age were associated with fewer IPC visits, suggesting that housework and obligations at the home may occupy as much or more of women's time compared to employment .The associations between combinations of intervention exposure or number of IPC contacts and IYCF practices present different scenarios across countries. In Bangladesh, any exposure appeared to be insufficient, and the frequency of contacts mattered for IYCF practices. Also, higher exposure to IPC was not associated with minimum dietary diversity or consumption of iron-rich foods in Bangladesh, which may suggest that these practices require inputs such as a variety of or specific nutrient-rich foods and are not adequately influenced by behavior change communication alone in this population. In Ethiopia, the combination of exposure to IPC and other intervention components and at least monthly IPC contacts was important for complementary feeding practices. In Vietnam, exposure to IPC alone and IPC with MM was associated with higher odds of EBF, as was exposure to ≥1 IPC contact. Even just 1 facility-based IPC contact appeared to be effective for EBF in Vietnam, which is corroborated by findings of significant improvements in IYCF counseling service quality as a result of incorporating the social franchising elements into government health care facilities .Our findings contribute to the evidence base on the implementation of behavior change interventions, particularly the combination of interventions and frequency of IPC or counseling contacts to improve child feeding practices. A systematic review on breastfeeding counseling showed that ≥4 contacts may reduce the likelihood of not exclusively breastfeeding, compared with standard care or no breastfeeding counseling . Our stuData from cross-sectional household surveys were used to assess intervention exposure, factors associated with exposure, and IYCF practices; thus, we cannot determine causal relations between them. The impact evaluation results have already proven the effectiveness of interventions, however, and our present findings are the result of closer examination at how these interventions were implemented and associated with the outcomes. Measures were based on maternal report and may be susceptible to recall bias. Feasible ranges and variability in indicators corroborated by process evaluation results and program reports strengthen our interpretation of results. Also, EBF practice was measured in our study based on mothers’ recall in the last 24 h rather than over the entire period since birth, but this standard point-in-time measure of current status helps to avoid the risk of recall error over a longer period and serves its purpose in our study for comparison across the 3 countries . While SIn conclusion, the combination of behavior change interventions and number of IPC contacts required to achieve IYCF behavior change seem to be very context specific. Further research to understand the relations between intervention exposure, individual characteristics, contexts, and benefits can help guide decisions about intervention planning and implementation at scale.nzz140_Supplemental_FileClick here for additional data file.


Physicians’ motivation plays a vital role in health systems particularly in dense and urban cities, which deal with high volumes of patients in a variety of settings. The loss of physicians due to low motivation to developed countries is also a critical aspect affecting the quality of care in many regions. Fewer studies have explored health provider and particularly physicians’ motivation in developing countries, which is critical to health service delivery. In addition, limited relevant tools have been developed and tested in low and middle-income settings like Pakistan. The purpose of this study was to create and test a tool for measuring physician motivation. A tool was developed to explore physicians’ motivation in the Lahore district, Pakistan. Three sections of the questionnaire, which included intrinsic, socio-cultural and organizational factors, were tested with a stratified, random sample of 360 physicians from the public and private health facilities. Factor analysis produced six factors for ‘intrinsic motivation,’ seven for ‘organizational motivation’ and three for ‘socio-cultural motivation’ that explained 47.7%, 52.6% and 40.6% of the total variance, respectively. Bartlett’s test of sphericity and the KMO were significant. Cronbach's α and confirmatory factor analysis were found satisfactory for all three sections of questionnaires. In addition to identifying important intrinsic, socio-cultural and organizational factors study found the questionnaires reliable and valid and recommend further testing the applicability of the instrument in similar and diverse settings. It has been estimated that the shortage of health care providers (HCP) is approximately 7.2 million, mostly in low and middle income settings of South Asia and Africa where the burden of disease is also high . UndoubtThe terms of motivation and job satisfaction have been defined by scholars extensively over the last few decades. In general, literature is suggestive of multidimensional and inter-related facets of motivation and job satisfaction determinants. According to Luthans, motivation can be defined as the process that arouses, energizes, directs, and sustains behavior and performance . Franco Unfortunately, though research on HCP has been conducted extensively in developed countries, little has been accomplished in developing countries , 17, 18.The overall study consisted of three components. Part one was comprised of semi-structured, open-ended questions about physicians’ work motivators and demotivators published elsewhere . The sec2) of Lahore, , Pakistan , personal values and ethics [four items], work interest and importance [four items], work pride and internal recognition [three items], self-actualization and esteem [three items] and intrinsic satisfaction and self-sufficiency [four items]. For ‘organizational motivation’, the seven factors (33 items) were labeled as working conditions and facilities (eight items), job roles and responsibilities (five items), work-related health and safety (three items), pay (four items), incentives other than salary (six items), resource availability (four items), and supervision (three items). For ‘socio-cultural motivation’ three factors (12 items) were labeled as work-related interpersonal relationships (five items), social recognition (three items) and personal life issues (four items).Confirmatory factor analyses for intrinsic, organizational and socio-cultural sections of the questionnaire are shown in Figs This study showed various known intrinsic, organizational and socio-cultural determinants of HCP motivation. Although literature shows overlapping and complexity in categorization of different individual items into intrinsic, organizational and socio-cultural factors Tables –3, it waAs with most tools, the possibility of response bias  may exist. In an effort to reduce this possibility, the instrument used no negatively worded items and local experts were involved throughout the process of tool development and analysis. Additionally, the self-administered questionnaires were returned anonymously. Another limitation of the study is the age bias of the respondents. Many of the physicians who participated in the study were younger and early in their career, which could have affected the outcome of the factor analysis. Nevertheless, the instrument is still applicable in this region, as the majority of practicing physicians in Pakistan are young, and the risk of emigration from rural to urban or to developed countries is the highest among this age group, since they are in the early stages of their career and are generally more mobile . A recomStudy findings provide evidence to support different aspects of Maslow's, Herzberg’s and ERG theories –46. In aOverall, factors found in the study also support the findings of prior research that money or financial incentives are not the only factors important for HCP motivation in other low and middle income countries , 64, 65.In Pakistan, fewer studies conducted on health providers’ motivation and/or job satisfaction have also found many factors that are comparable to the tool findings. Mostly studies have explored the issue in general using tools previously used in other developed countries or dissimilar settings with no or different categorization of determinants , 76, 77.In addition to the development of a valid and reliable tool to explore motivation, this study identified important intrinsic, socio-cultural and organizational factors behind physician motivation and job satisfaction in this region. Considering limited studies and tools developed and tested on this issue in the region, study findings can potentially assist managers and policy makers to identify feasible determinants to deal with in resource limited settings like Pakistan. Findings also highlight the need for further investigations across different health facilities to assist in policy planning and interventions, particularly in low and middle-income countries.S1 Data(SAV)Click here for additional data file.S1 Questionnaire(PDF)Click here for additional data file.


Molecules, as one year ends and another starts its Publisher and Editor-in-Chief would like to take stock of our progress in 2008 and offer our readership a preview of things to come in 2009. Just as we had hoped in last year’s editorial [Molecules. By year’s end we had published 239 papers and three Editorials or Editor's Notes for a total of 3,252 pages. While the 8% growth in the number of papers published compared to 2007 may appear modest, the number of pages published represented a 22% increase over the prior year, and was largely attributable to the increase in the number of reviews published. As has now become a custom for ditorial , the yeaPhenolics and Polyphenolics, 5-Fluorouracil, Prodrugs, Alkaloids and Spirocompounds, whose Guest Editors, Professors Pereira and Andrade, Puoci, Vanden Eynde, Valentao and Plourde shall continue to work on the manuscripts submitted for these issues that will continue to appear in the coming months, as they make their way through the peer review process. These Guest Editors will be joined in 2009 by those from our lengthy list of planned new special issues: Macromolecules Applied to Pharmaceutics (Coviello); Dynamic Combinatorial Chemistry (Otto); Acetogenins: Extraction, Synthesis and Biological Properties ; Coumarins and Xanthones (Richomme); Neglected Diseases: Medicinal Chemistry and Natural Product Chemistry (Batista); Nucleic Acids (Carlsen); Triterpenes and Triterpenoids (Roussis); Biodegradation: Organic, Medicinal and Analytical Chemistry (Lin and Teramoto); Dendrimers – From Synthesis to Applications (Zhang); Ferrocenes (Ríos Torres); Microwave Assisted Synthesis (Seijas Vázquez); Organocatalysis (Zhong); Quinones and Hydroquinones: Target Molecules and Building Blocks (Spyroudis); Selenium and Tellurium Chemistry (Pietschnig); Alpha- or Beta-aminophosphonates and -phosphinates ; Aporphines and Oxaporphines (Sobarzo-Sánchez); Baylis-Hillman Reaction and Related Processes (Li); Ionic Liquids (Bonrath) and Sonochemistry – Organic Synthesis (Bonrath). Last year also saw the passing of the submission deadlines for some of the special issues carried over from the previous year, like those dedicated to Molecules is now indexed and/or abstracted in PubMed/Medline; Beilstein CrossFire; Chemical Abstracts (CAplus); Science Citation Index Expanded; Chemistry Citation Index; Current Contents/Physical, Chemical & Earth Sciences; SciSearch; Research Alert; Scopus; Google Scholar; IndexCopernicus; Journal Citation Report; Scirus; Directory of Open Access Journals (DOAJ) and Open-J-Gate, so authors may be assured of the prompt and widest possible dissemination of their results. We are also happy to note that as the Publisher anticipated in a previous Editorial , the movGeneral Editorial Board, which had remained essentially unchanged for the past 13 years since we started publication. We are extremely pleased to report that new names of the highest caliber have been added, while many of the luminaries already on our Board, including three Nobel Prize winners, graciously agreed to extend their relationship with Molecules. Also in 2008 we renewed the composition of our www.mdpi.com, where we offer an appealing new layout complete with graphical abstracts, powerful search and document export features and access to papers within 1-2 days of acceptance for publication, rather than on a monthly basis when the issues are released as was previously the case. In 2008, DOI numbers were added for all papers published in MDPI journals. Though all the pdf files of the papers published and indexed in many databases are still available from the www.mdpi.org server, complete sets of the all the papers are now available at www.mdpi.com. This progress can be duly attributed to Dietrich Rordorf and his software development and data management team members Marc Bigler, Robert Seibert and Daniel Schmutz.Finally, readers will have noticed our move to a new publication platform at lin@mdpi.org.In conclusion, as 2009 begins, we take this opportunity to offer our best wishes and thanks to our many authors, anonymous peer-reviewers and readers for their continued support of our efforts and our Assistant Editors Ms Felicity Wright and Ms Jely He at our Basel and Beijing offices, respectively, for their hard work handling the submission and peer review process. As always, we welcome your comments on these matters. Messages with a suitable subject header may be sent to


Like other subjects, forensic genetics gradually emerged and developed through long-term social practice. Following the discovery of the ABO blood groups by Landsteiner in 1900  and statOne of the central aspects of forensic genetics is the use of genetic markers, which are the easily identifiable phenotypes of genotypes. Genetic markers generally have features such as strong polymorphisms, codominant expression and ease of observation and recording. With the development of genetics, the use of genetic markers has also developed steadily. To date, the development of genetic markers has gone through four major stages characterized by the use of morphological markers, cytological markers, biochemical markers and molecular markers. In particular, this present special issue provides an introduction to the application and development for molecular markers in forensic areas.TH01, vWA, FES/FPS and F13A1. Today, commercial STR kits can generally detect 15–20 STR loci at one time. With the advancement of fluorescent marker techniques, six-color fluorescent marker STR kits have appeared on the market, and 25–30 STR loci can be detected. The International Society for Forensic Genetics (ISFG) has drafted a guide to the forensic validation of STR kits, and this guide provides excellent standards and guidance for the forensic application of STR kits.During the early 1990s, short tandem repeats (STRs) were used for the first time as key molecular markers in human paternity testing. The first forensic multiplex amplification STR kit was developed by Britain’s Forensic Science Service (FSS) and included four genetic loci: The rapid development of massively parallel sequencing (MPS) has attracted widespread attention among forensic genetics researchers. STR typing based on capillary electrophoresis can only reflect differences in length; however, MPS can also reveal differences in the internal sequence and flanking structure of STRs, which tremendously increases the available genetic information and provides a new possible method for difficult cases involving complex kinship identification and the resolution of mixtures. In addition, the development of MPS has also promoted metagenomics research. In recent years, metagenomics has developed as a new branch of microbial ecology that addresses the microbial composition and diversity of different environments, and microbial community members’ relationships with each other and their environment. Metagenomics is gradually being applied in areas connected with forensic identification such as individual identification, identification of the source of biological stains in crime scenes and the detection of drug abuse, which has also brought new research opportunities.−8 [Since forensic polymorphic STR loci are limited in number and cannot provide more functional information, which hampers the effectiveness of the application in forensic community, a new type of genetic marker, single nucleotide polymorphisms (SNPs), may replace STRs in the future, although this process may take a considerable period of time. Compared with STR loci, SNP sites have a lower mutation rate, approximately 10−8 , and theScience as a major scientific breakthrough. A series of groundbreaking advances in RNA research during the past 20 years have enabled RNA to escape from the brilliance of DNA’s aura, have changed RNA from the “supporting role” to the “leading role” and have made RNA a new challenge to DNA’s central position. In the field of forensics, steady progress is being made in applied research involving the use of RNA to identify racial affiliation, the identification of bodily fluids, the determination of time of death and the analysis of injuries. In addition, thanks to their advantages of convenience, economy, speed and precision, protein-level genetic markers offer great promise in forensic genetics and related fields.Apart from DNA-level genetic markers, RNA-level genetic markers have also become a new type of marker and research hotspot in forensic genetics. In 2000, progress in RNA research was acclaimed by In summary, the application of genetic markers has advanced in pace with the scientific knowledge and technological capabilities, which has expanded and changed the scope of forensic genetics research. From the dual perspectives of the development of genetic markers and their applications, the papers in this special issue explain that forensic genetics research is no longer limited to DNA-level markers but also includes RNA-level and protein-level markers. The scope of forensic genetics research is no longer limited to conventional determination of kinship and individual identification; it has steadily branched out into areas such as forensic clinical medicine, forensic pathology and forensic psychiatry, yielding many new findings and applications.


Law lies at the centre of successful national strategies for prevention and control of noncommunicable diseases. By law we mean international agreements, national and subnational legislation, regulations and other executive instruments, and decisions of courts and tribunals. However, the vital role of law in global health development is often poorly understood, and eclipsed by other disciplines such as medicine, public health and economics. This paper identifies key areas of intersection between law and noncommunicable diseases, beginning with the role of law as a tool for implementing policies for prevention and control of leading risk factors. We identify actions that the World Health Organization and its partners could take to mobilize the legal workforce, strengthen legal capacity and support effective use of law at the national level. Legal and regulatory actions must move to the centre of national noncommunicable disease action plans. This requires high-level leadership from global and national leaders, enacting evidence-based legislation and building legal capacities. Noncommunicable diseases, including cardiovascular disease, cancer, respiratory diseases and diabetes, cause an estimated 41 million deaths each year.Box 1Overall target:by 2025, a 25% relative reduction in mortality from cardiovascular disease, cancer, diabetes and chronic respiratory diseases in persons aged 30–70 years.Eight supporting targets:10% relative reduction in harmful use of alcohol;10% relative reduction in prevalence of physical inactivity;30% relative reduction in mean average population salt intake;30% relative reduction in prevalence of tobacco use (persons older than 15 years);25% relative reduction in raised blood pressure;0% increase in diabetes and obesity;50% coverage for drug therapy and counselling for those at risk for cardiovascular disease;80% coverage of affordable technologies and essential medicines for treating noncommunicable diseases in both public and private facilities.Target 3.4: by 2030, reduce by one third premature mortality from noncommunicable diseases through prevention and treatment and promote mental health and wellbeing.The effective use of law and regulation lies at the heart of successful national noncommunicable disease action plans.Box 2The World Health Organization’s (WHO) work at the intersection of law and noncommunicable diseases includes:supporting governments to develop laws and regulations on health matters through technical assistance, training and provision of technical resources;comparative analysis of laws in different jurisdictions for WHO publications, including biannual reports on the global tobacco burden;analysing litigation and industry opposition to policies and laws, and integrating lessons learnt into technical assistance and resources;gathering evidence in support of effective public health laws and policies in Member States;providing assistance to Member States in litigation matters;–intervening in legal disputes; for example, through the amicus briefs filed in disputes over tobacco control lawsengaging with other inter-governmental organizations on legal and normative issues.This paper identifies some important areas of intersection between law and prevention and control of noncommunicable diseases, arguing that law lies at the centre of effective action. We suggest actions that WHO and other health development partners could take to strengthen national legal capacities and accelerate implementation of legal and regulatory strategies.,In 2017, the World Health Assembly endorsed an updated set of policy options and cost–effective interventions for reducing the burden of noncommunicable diseases, including minimizing the major risk factors .Box 3Highly cost–effective policy interventions (best-buys) recommended by the World Health Organization include:increasing excise taxes and prices of tobacco products and alcoholic beverages;eliminating peoples’ exposure to second-hand tobacco smoke in all indoor workplaces, public places and public transport;comprehensive bans on tobacco advertising, promotion and sponsorship;implementing plain tobacco packaging and/or graphic health warnings on all tobacco packages;comprehensive bans or restrictions on alcohol advertising across multiple forms of media;enforcing restrictions on the physical availability of alcohol via reduced hours of sale in retail outlets;mandatory product reformulation and front-of-pack labelling to help people to reduce salt intake.Other cost–effective policy interventions include:implementing and enforcing drink-driving laws and blood alcohol concentration limits via sobriety checkpoints;eliminating industrial trans-fats through legislation banning their use in food manufacturing;taxation of sugar-sweetened beverages at a rate high enough to encourage people to reduce sugar consumption.Other recommended, legally-oriented policy options include:measures to minimize illicit trade in tobacco products;bans on cross-border tobacco advertising;setting minimum alcohol prices;enforcing a minimum age for purchase of alcoholic beverages;reducing the density of retail alcohol outlets;restricting or banning promotions of alcoholic beverages targeting young people;requiring labels for alcoholic beverages to include information about the harm caused by alcohol;implementing subsidies to increase people’s intake of fruits and vegetables;replacing trans-fats and saturated fats with unsaturated fats through mandatory reformulation, product labelling, fiscal or agricultural policies;implementing nutrition labelling to encourage people to reduce consumption of energy, sugars, sodium and fats;improving urban environments to ensure ease of walking, connectivity and access to public transport to encourage people to engage in more physical activity.Source: World Health Organization.,,The force of law is needed to implement effective policies for prevention and control of noncommunicable disease risks because voluntary implementation will rarely be in the commercial interests of food, alcohol and tobacco companies. There are similarities in the ways these industries seek to influence not only legislative outcomes, but also the perceptions of politicians and the public, the framing of issues for debate and the generation of favourable evidence.Apart from seeking to reduce noncommunicable disease risk factors, law is an important tool for establishing institutional and governance mechanisms to support public health functions. For example, Samoa’s Health Promotion Act, enacted in 2013, established the Samoa Health Promotion Foundation, giving it a legislative mandate to engage in health promotion, fund research and advise the health minister.–The constitution of many countries guarantees health-related rights to their population.Box 4Constitutional rights may provide remedies for groups harmed by government or corporate actions or omissions:In India, individuals may petition the Supreme Court to enforce fundamental rights and liberties in the Indian Constitution. The Supreme Court has ruled that the exposure of non-smokers to tobacco smoke violates the constitutional right to life and personal liberty.The High Court of Uganda has ruled that the emission of tobacco smoke, dust and smell from a tobacco factory in a residential area violates the right to a healthy and clean environment, as protected in the Ugandan Constitution.A Colombian civil society organization, Educar Consumidores, successfully challenged an order given by a regulatory authority, the Superintendency of Industry and Commerce, directing Educar Consumidores to cease transmission of a television and radio campaign that pointed to the quantities of sugar in sugary drinks and their harmful effects. Educar Consumidores and representatives of another civil society organisation successfully petitioned for review by the Colombian Constitutional Court, which held that the ban violated consumers’ constitutional right to receive information – and to inform others – about the health risks of sugary drinks.On the other hand, constitutional rights may conflict with public health policies on noncommunicable diseases:The city of San Francisco passed a local ordinance requiring billboards advertising soda drinks to display a warning that added sugars contribute to obesity, diabetes and tooth decay. In response, the American Beverage Association obtained an injunction on the basis that a mandatory warning infringed their First Amendment rights to free speech.On the other hand, national constitutions typically protect a range of non-health-related rights that may conflict with public health policies. In some countries, the right to freedom of expression protects commercial speech, which may undermine efforts to restrict the marketing of tobacco, alcohol, unhealthy food and drinks, and breastmilk substitutes. Civil society organizations have also relied successfully on the right to freedom of expression to resist efforts to supress information about the health effects of sugary drinks, as illustrated by an example from Colombia .25International law can also influence national policies on noncommunicable disease prevention and control. For example, parties to the WHO Framework Convention on Tobacco Control have assumed an obligation under international law to implement policies on reduction in demand and supply of tobacco products.Unlike the WHO Framework Convention on Tobacco Control, health-related provisions in human rights treaties are often expressed in general terms and were not framed with noncommunicable disease risk factors in mind.Each country’s compliance with its human rights obligations is reviewed through a process known as Universal Periodic Review, overseen by the UN Human Rights Council. Universal Periodic Review provides an impetus for governments to strengthen health-related rights,International human rights law and practice is a neglected resource for governments seeking to reduce the burden of noncommunicable diseases. Analysis of specific health rights within international human rights agreements provides important guidance in many areas, such as tobacco control and marketing of foods and beverages.International trade law is another important area of law that impacts on risk factors for noncommunicable diseases. International trade and investment agreements can affect noncommunicable disease risk factors in complex ways; for example, by reducing prices, increasing competition, and facilitating international trade and investment in harmful products, such as tobacco and alcohol.In legal terms, trade and investment agreements discipline how states can regulate. For example, World Trade Organization (WTO) law establishes core principles of trade law, including prohibiting discriminatory regulation, requiring that regulation be not more trade restrictive than necessary to protect health, and requiring minimum standards of protection for intellectual property rights. The WTO panels have applied these principles in adjudicating legal disputes concerning tobacco control. For example, a WTO panel held that United States legislation banning flavoured tobacco, but exempting menthol-flavoured products discriminated in favour of domestic products.Regional trade agreements are increasingly important. Customs unions, such as the European Union, can lead to harmonization of laws, such as through the 2014 European Tobacco Products Directive.,Investment treaties, whether bilateral or as investment chapters in trade agreements, can also impact on legislation concerning noncommunicable diseases. The tobacco company Philip Morris International recently challenged tobacco control laws in Australia and Uruguay. These claims, which were unsuccessful but expensive to defend, concerned plain tobacco packaging, health warnings and other labelling requirements implemented in response to the WHO Framework Convention on Tobacco Control.Challenges to policies for prevention and control of noncommunicable diseases are frequently resolved in national courts and tribunals, as illustrated again by the alcohol industry’s 5-year attempt to overturn Scotland’s legislation on minimum alcohol pricing.On the other hand, litigation and use of other complaints mechanisms can be used to hold industry to account for harm caused by their products, to improve access to medicines and to vindicate other health-related rights.Legislation and executive actions are essential for noncommunicable disease prevention and control, while many of the challenges to effective national plans, such as defending litigation initiated by industry, also call for technical legal expertise. However, governments face major obstacles to using law effectively, including lack of trained personnel, lobbying by powerful industry groups and uncertainty about the extent of their country’s obligations under trade and investment agreements.Box 5,In 2015, the Chilean Ministry of Health published regulations on the nutritional composition of food products, implementing an earlier law passed in 2012.Mexico’s 1 peso per litre tax on sugar-sweetened drinks, implemented in 2014, resulted in a seasonally adjusted reduction in consumption of taxed beverages of 5.5% in 2014, and 9.7% in 2015, compared with estimates based on trends in consumption before the implementation of the tax.In 2013, South Africa introduced regulations under its Foodstuffs, Cosmetics and Disinfectants Act to impose maximum limits for sodium across 13 categories of food including bread, breakfast cereal and porridge, processed meat, savoury snacks and potato chips.Effective from April 2018, the soft drinks levy introduced in the United Kingdom has two tax levels that apply according to the sugar content: 18 pence for drinks with > 5 g sugar per 100 mL, and 24 pence for drinks with > 8 g sugar per 100 mL.,Six States  and more than 350 cities and counties, including New York city, have raised the minimum purchasing age for tobacco from 18 to 21 years.Public health advocates have called on the World Health Assembly to make bold use of its legal powers, through a convention on alcoholic beveragesThe WHO Independent High-level Commission on noncommunicable diseases encouraged governments to use their “full legal and fiscal powers to achieve public health goals.”WHO could also facilitate the diffusion of policy across Member States by creating opportunities for governments that are leading the way to share their practical experiences of drafting, implementing and enforcing laws and fiscal policies.Building legal capacity means mobilizing a workforce with the technical skills to navigate legal issues arising in key areas of noncommunicable disease prevention and control.Leadership requires greater investment in legal capacity within WHO and other agencies working in health development, and careful assembling of a legal workforce. Donor funding for a dedicated public health law programme within WHO to support countries in implementing best-buy policy interventions could have a substantial impact.First, WHO could facilitate professional exchanges and mutual support among those who use legal knowledge in key practice areas. Fostering such a transnational network could be achieved online, with support for legal practitioners working in key thematic areas, countries and regions, and in different languages. With appropriate support, these communities of practice will grow and evolve, seeking out strategic opportunities, developing novel legal arguments, providing expert evidence in litigation (through filing of amicus briefs), documenting case studies and developing technical resources in areas of need.Second, knowledge provides the foundation for action. In the context of tobacco control, for example, databases of case law and legislation facilitate comparative analysis and assist lawyers and health professionals to anticipate tobacco industry strategies.Although prevention and control of noncommunicable diseases ideally require a national response, state, city and local governments can be powerful innovators . Unlike Local governments have been leaders in many areas of noncommunicable disease policy. In the United States, local jurisdictions were the first to impose higher taxes, marketing restrictions and bans on smoking in public places, among other interventions.Regionally coordinated action can accelerate the implementation of legislation, particularly by smaller countries. The best opportunities exist in regions that have a strong history of cooperative action. WHO’s regional offices and other regional political groupings  could lead, coordinate and support national noncommunicable disease policies. Deliberate, planned, regional action could benefit small, remote and vulnerable populations whose governments may otherwise engage in prevention and control in a piecemeal fashion and at a slower rate. Regional action allows more efficient use of legal resources, although careful groundwork is needed to create a shared vision and agreed principles for action. Box 6The World Health Organization Regional Office for the Eastern Mediterranean (WHO-EMRO), partnered with the O’Neill Institute for National and Global Health Law at Georgetown University, Washington, United Sates of America, to spur legal reform for noncommunicable disease prevention and control. The project identified affordable, feasible and cost–effective legislative and regulatory interventions that were suitable for implementation in the Eastern Mediterranean Region.The comprehensive dashboard of legal interventions proposed that WHO-EMRO Member States prioritize interventions in three key domains: (i) noncommunicable disease governance mechanisms requiring multisectoral collaboration, accountability and transparency; (ii) tobacco control laws in compliance with the WHO Framework Convention on Tobacco Control;WHO-EMRO committed to support Member States to enact and enforce population health improvements through these priority interventions. The project includes implementation guidance tools as well as capacity-building initiatives led by multidisciplinary teams of legislators and public health experts.Legislative and regulatory actions lie at the heart of successful national and local strategies for noncommunicable disease prevention and control. However, the role of law as a public policy tool, translating scientific evidence and normative guidance into action, receives inadequate attention amid the dominance of other disciplines in global health development. This needs to change. Rapid progress in tobacco control has not been accidental, but reflects agreement about the critical importance of law to tobacco control – leading, in turn to adoption of strong, legally-binding standards at international and national levels. The rapid progress also reflects global investment in capacity-building, technical assistance to WHO Member States, and expansion of legal resources, assisted by organizations such as Bloomberg Philanthropies and the Bill & Melinda Gates Foundation. These factors, which have accelerated progress in tobacco control, are not yet present for other noncommunicable disease risk factors such as unhealthy diets and harmful use of alcohol. Legal and regulatory action must move to the centre of national noncommunicable disease action plans. This requires high-level leadership at global and national levels, developing evidence-based legislation through transparent processes, enforcing it, evaluating its effectiveness and building legal capacities.


Stroke and transient ischaemic attack (TIA) remain leading causes of mortality and morbidity globally. Although mortality rates have been in decline, the number of people affected by stroke has risen. These patients have a range of long-term needs and often present to primary care. Furthermore, many of these patients have multimorbidities which increase the complexity of their healthcare. Long-term impacts from stroke/TIA along with care needs for other morbidities can be challenging to address because care can involve different healthcare professionals, both specialist and generalist. In the ideal model of care, such professionals would work collaboratively to provide care. Despite the commonality of multimorbidity in stroke/TIA, gaps in the literature remain, particularly limited knowledge of pairings or clusters of comorbid conditions and the extent to which these are interrelated. Moreover, integrated care practices are less well understood and remain variable in practice. This article argues that it is important to understand (through research) patterns of multimorbidity, including number, common clusters and types of comorbidities, and current interprofessional practice to inform future directions to improve long-term care. The two most frequent physical comorbidities for those with a diagnosis of stroke were hypertension and coronary heart disease, consistent with other studies  across 56 conditions found that of 4.2 million UK adults, 229 205 individuals experienced cardiovascular disease  and timespan in which comorbid conditions present in relation to stroke/TIA also need further exploration given subsequent implications on treatment, care management, and health service financing and planning ’ , some are decades old  those that are focussed on a specific disease  and include other conditions as comorbid; (ii) those that are focussed on specific combinations of a number of chronic diseases; and (iii) those that are not confined to specific combinations of chronic diseases  in different countries , as well as different care settings  to contribute to the ‘global atlas’ of multimorbidity  identifying their risk factors for developing further morbidity, and/or experiencing another stroke or TIA and (ii) developing context-appropriate strategies for addressing wide-ranging and long-term needs, such as cognitive impairment and rehabilitation. From this understanding, new models of integrated care practices can be developed, informed by evidence and current effective integrated care practices. The landmark Alma-Ata Declaration’s 40