In South Africa, stigma, discrimination, social visibility and fear of loss of confidentiality impede health facility-based HIV testing. With 50% of adults having ever tested for HIV in their lifetime, private, alternative testing options are urgently needed. Non-invasive, oral self-tests offer a potential for a confidential, unsupervised HIV self-testing option, but global data are limited.A pilot cross-sectional study was conducted from January to June 2012 in health care workers based at the University of Cape Town, South Africa. An innovative, unsupervised, self-testing strategy was evaluated for feasibility; defined as completion of self-testing process . An oral point-of-care HIV test, an Internet and paper-based self-test HIV applications, and mobile phones were synergized to create an unsupervised strategy. Self-tests were additionally confirmed with rapid tests on site and laboratory tests. Of 270 health care workers , 251 consented for participation.Overall, about 91% participants rated a positive experience with the strategy. Of 251 participants, 126 evaluated the Internet and 125 the paper-based application successfully; completion rate of 99.2%. All sero-positives were linked to treatment . About half of sero-negatives were offered counselling on mobile phones; completion rate: 44.6% . A majority of participants (78.1%) were females, aged 18–24 years (61.4%). Nine participants were found sero-positive after confirmatory tests . Six of nine positive self-tests were accurately interpreted; sensitivity: 66.7% ; specificity:100% .Our unsupervised self-testing strategy was feasible to operationalize in health care workers in South Africa. Linkages were successfully operationalized with mobile phones in all sero-positives and about half of the sero-negatives sought post-test counselling. Controlled trials and implementation research studies are needed before a scale-up is considered. A vast proportion of HIV infected individuals worldwide (6/10) do not know their serostatus Knowledge of HIV sero-status with self-tests could influence risk-taking behaviours and impact risk reduction South Africa has the world's highest global HIV/AIDS burden Despite availability of generic antiretroviral treatment, an early engagement to care is not yet a reality in South Africa. There is an urgent need to arrange for private and confidential alternatives to facility-based testing. To address this public health need, we developed an innovative, synergistic, HIV self-testing strategy that can be performed with oral HIV tests, and in future, in the comforts of one's own home. We evaluated this strategy in a population of health care workers (HCW) from the University of Cape Town. HCW are at a high risk of getting infected with HIV because of the nature of their profession, are anecdotally known to self-test for HIV, but less likely to engage in testing due to fear of loss of confidentiality, privacy and social visibility associated with facility based tests Self-testing is a process that requires a certain level of self-motivation to purchase the test, perform the test properly, interpret the self-test result accurately, and proactively seek linkages to counselling, confirmatory testing or treatment (as the case may be) by contacting a counsellor or health center, either in person or on phone or internet In a recent systematic review, we summarized global evidence on the two self-testing strategies that have been evaluated worldwide In this report, we present results from a pilot cross sectional study that evaluated an unsupervised self-testing strategy evaluated in HCWs. We primarily estimated feasibility of the self-testing strategy defined by the completion rate . Our secondary objectives were to: 1) evaluate the self-test's accuracy, 2) document participant preferences, concerns and experience with the self-testing strategy, and, 3) evaluate HIV sero-positivity.Two Institutional Review Boards based at McGill University Health Centre Montreal, Canada and at the University of Cape Town, South Africa approved the study. Written informed consent was obtained from all participants. Research was conducted in accordance with the principles expressed in the Declaration of Helsinki.Our innovative strategy consisted of two self-testing applications; internet-based and paper-based refer . These wBetween January and June 2012, we enrolled 251 HCW  in a cross-sectional study at Groote Schurr Hospital, a tertiary care centre in Cape Town, South Africa. HCWs who spoke English, were 18 years of age or older, of undocumented HIV sero-status at baseline (i.e. the participant was unaware of his/her sero-status) and were able to provide informed consent were recruited. This population was chosen because: a) HCWs are at risk for HIV occupationally and are anecdotally known to self-test, and, b) they may benefit from a private HIV self-testing option that averts perceived stigma and discrimination associated with seeking an HIV test in the work place, and lastly, c) the population was digitally literate, and desired to try out an unsupervised self-testing strategy. The study was funded by Grand Challenges Canada. The oral test used in our study, Oraquick (R) HIV1/2  is an FDA approved, CE marked test that is approved for sale and use in South Africa.Study flyers and pamphlets were pasted across the hospital campus with the phone number and interested participants contacted the research nurse. A convenient sample of HCW who showed up and consented to the study procedures was recruited. Participants were offered a choice of self-testing applications over the Internet and on paper. They chose the Internet or paper-based application according to their comfort and preference levels.After informed consent was sought, the research nurse led participants to a private room equipped with a computer with Internet access, a landline and a mobile phone, and an oral self-test. Our internet-based self-testing application was administered online. Refer  At any tThe paper based application refer:  and procIn parallel, blood was drawn on site from each participant for confirmatory rapid and laboratory based testing and sent to the reference laboratories linked by Study IDs for confirmatory testing. A standard National Health Laboratory Services  approved HIV testing algorithm was used for confirmatory testing  and Western Blot for positives). Additionally, study ID linked rapid HIV tests SD Bio line HIV Rapid Test [Anti-HIV 1/2]  and Determine™ HIV 1/2 Ag/Ab Combo  were performed on site.Participants who tested positive with in-house rapid tests were flagged for expedited confirmatory laboratory testing and results were made available within 8 hours. All the participants were encouraged to call the counsellor for post-test counselling. Additionally, all house tested (rapid test) sero-positives, after receipt of expedited lab confirmed sero-positives were contacted by the counsellors to communicate and confirm their test results, offer post-test counselling, advice for ART staging and arranged for confidential referrals to a clinic of the participant's choice. All these services were operationalized using mobile phone calls and text services.Lab confirmed test results for participants that tested negative with in-house rapid tests were available within the next working day. All self test negative participants who called were offered risk reduction counselling. Data was confidentially collected online using our Internet application and was exported into an EXCEL sheet linked by study ID. Data from paper-based application were manually entered in an EXCEL file. Both the data sets were merged and then analyzed in STATA version 10 . With a hypothesized completion rate of the self-testing process at 80%, a sample size of 251 gave us 95% confidence interval (CI) widths of +/−0.049. Data on demographics and risk factors were reported as proportions with 95% CI.Of 270 participants that were approached for study participation, 251 (93.0%) consented, of which 126 completed the internet-based application, and about 125 completed paper-based application . Of 251 About nine positives were identified, of which six accurately interpreted their self-test result. The other three participants' reported their self-test result as ‘negative’ whereas, the in-house rapid and confirmatory tests results were ‘positive’. The research nurse called the participants after the receipt of lab confirmed results as per IRB protocols. Their oral self-tests were performed again. On repeating these tests, two of the three participants self reported having seen a faint positive line on initial testing. On repeat testing, the faint positive lines persisted and were confirmed by the nurse to be positive. This suggests that self-testers may fail to read/interpret a faint or weak positive line as a positive self-test. At that time, our application did not have any information on the interpretation of faint positive lines. We incorporated the fact that any line  was to be read as a positive line after completion of the study. The sole participant who was missed by a self-test was a false negative, who correctly interpreted his/her self-test result as negative with the antibody test, and the test failed him/her. This was because of a lack of p24 antigen in the test device that is antibody based that fails to detect sero-conversion. Information on this issue was included in the application.In terms of linkages, through the use of mobile phones and confidential text messaging, all nine sero-positives received post-test counselling before ART staging and initiation, and were offered expedited and confidential linkage to care to a clinic of their choice. Therefore, our completion rates for linkages in nine seropositive were: 100% . Likewise, in 242 sero-negatives, about half of sero-negatives called for counselling on mobile phones, giving us a completion rate for linkages in sero-negatives at 44.6% .HIV prevalence (sero-positivity) in our study sample was 3.6% . With nine seropositives and 242 seronegatives, the sensitivity of reading self-tests compared to lab confirmed test results was 66.7% , and specificity was 100% , However, our positive predictive value (PPV) remained at 100%  and our negative predictive value (NPV) was at 98.8% . Sensitivity of self tests could certainly be improved with a call for development of antibody and antigen combined self tests that can quickly detect sero-conversion. One of these tests (Determine Alere Antibody/Antigen) combo test that is recently approved was used by us as in house rapid test.Demographically, a majority of our participants, , were females. About 61.4% (154/251) were aged 18–24 years, and  had completed high school. For further details on demographics, refer to Regarding self-testing experience, 91.2% (229/251) rated the experience as ‘very good’ or ‘good’ because of the privacy it offered, ease of use and non-invasive and painless nature of oral testing. For counselling, face-to-face counselling was an option acceptable to most participants , followed by technology enabled counselling  at 40.6% (95/234) for post-test counselling, linkages and referrals.On cost preferences, 93.2% (234/251) were willing to buy the oral self-test, with 57.7% (135/234) ready to pay R 1–50 (USD 0.10–6.30).Other responses to our open-ended questions regarding concerns and challenges have been summarized in We evaluated an unsupervised self-testing strategy using an Internet application and its paper equivalent in a population of HCWs, who wanted to learn about their HIV status with an oral self-test and a novel approach. Despite their occupational risk for HIV, and despite their residing for years in a high endemic setting, a substantial proportion (63%) of participants reported not seeking an HIV test in the past six months. Our confidential self-testing strategy was well received, with 100% linkages for sero-positives operationalized within 24 hours and post-test counselling for sero-negatives offered to 44.6% participants. Additionally, a high proportion of participants (91%) reported an overall positive self-test experience. Similar findings on acceptability and preference have been reported in various other studies that have evaluated self-testing strategies Completion rate of linkages in sero-negatives was lower compared to sero-positives at 44.6%, but higher than the 29.2% statistic traditionally reported from other facility-based testing projects Results however need to be confirmed in other at risk populations such as men who have sex with men, commercial sex workers, and young pregnant women that have a high HIV burden that may also desire confidential and personalized self-testing. Linkage data for self-testing initiatives are currently limited; therefore the study adds new important data from South Africa.Regarding diagnostic performance, the PPV, NPV, and specificity values of the self-test were high, but due to the low number of true self-test positives, our sensitivity estimates were low. Three self-test ‘negative’ participants who were contacted later voluntarily showed up for re-testing. Upon re-testing, two of three ‘negative self tests’ were discovered to have had faint positive lines self interpreted as ‘negative’ thus, highlighting the possibility of user errors in conduct and interpretation. In our study id linked positive sero-status was confirmed with the in-house rapid test and additionally, with laboratory confirmed test results, which were given by the research nurse to the participant. Interpreting faint positive lines was not included in our initial versions of self-testing applications, and this may have impacted participants' interpretation of a line. Interestingly, faint lines were also recently reported in the FDA document for approval of the self-test in the United States Besides, expedited confirmatory and in house rapid testing also picked up the lone self-test negative tester that was not picked up by the oral antibody-based test because of sero-conversion. To further analyze this finding, we know that the oral antibody-based self-test is very sensitive at and after 90 days, therefore, the self-testers must be encouraged to re-test themselves after 90 days, particularly, if there is a high suspicion of a recent exposure, or a perceived risk of having an acute infection but the self test is found to be negative in these situations.To conclude, the occurrence of user errors and inability of the test to pick up early/acute infection highlights the importance of providing clear instructions to the self-testers including limitations of self tests. Clear instructions on paper, the internet or on smartphone applications facilitate interpretation and enhance accurate performance of self-tests. Instructions will help avoid many errors in future. It is important to educate the public about the limitation of antibody-based test At the FDA deliberations over approval of self-tests, arguments of access to HIV testing, won over arguments of sensitivity. Additionally, we have recently reviewed global evidence on the accuracy of these oral rapid antibody tests in an implementation research context. We found them to be 98.03% sensitive  and 99.74%  specific in research settings This pilot study was conducted in a convenient sample of HCWs who consented to the evaluation of an unsupervised oral fluid based self-testing strategy. Selection and volunteer bias are likely. Misclassification of self-test results could lead to a potential for information bias.Although the pilot study was successful, it needs to be repeated in other at risk populations to generate stronger evidence for feasibility of this strategy. These studies are being planned in scale up of this project. The study results are generalizable to HCWs who would show up for participation if a supervised self-testing strategy were offered again at any of the hospitals. Future scale up studies that evaluate innovative interventions in at risk populations such as men who have sex with men, pregnant women, commercial sex workers and adolescents will serve to generate stronger evidence of generalizability to at risk populations. Although in a high endemic setting, one could argue that routine HIV testing should be conducted in all populations and more so in populations that are at risk in hospitals and other health care settings.To conclude, self-testing offers a discreet, viable, private, option to test provided confidentiality is maintained and expedited linkages within a reasonable time window are made available. Our study demonstrates that linkages can be operationalized confidentially, and successfully with phones. Although our innovative, un-supervised self-testing strategy was well received by HCWs in South Africa, larger real life implementation research studies and controlled trials on self-testing are urgently needed to generate stronger evidence for scale up. Following up on a recent call from the WHO for pilot feasibility studies, this study has generated data on feasibility. Our findings have implications for future planning of scale up studies for Southern African region and similar regions and settings in Asia.


World population has experienced continuous growth since 1400 A.D. Current projections show a continued increase - but a steady decline in the population growth rate - with the number expected to reach between 8 and 10.5 billion people within 40 years. The elderly population is rapidly rising: in 1950 there were 205 million people aged 60 or older, while in 2000 there were 606 million. By 2050, the global population aged 60 or over is projected to expand by more than three times, reaching nearly 2 billion people . Here we Elderly patients represent a unique and challenging group of patients to the practicing oncologist. They represent a heterogeneous group in terms of comorbidities and functional status which makes it difficult to establish management recommendation. One of the cancer pathways that is of interest in the elderly is the immune system and its role in oncogenesis and as potential therapeutic targets. In this review we present an overview of the changes in the immune system and the use of cancer vaccines in the elderly. We will also discuss the assessment of elderly patient with cancer.+ and CD8+ T-cells [+ B cells that are more likely to generate auto-antibodies [Aging is a process characterized by progressive functional decrease in all organs, morphological changes, and immune system-related changes at the cellular and molecular levels, which determine less adaptive biologic functions. The immune system alterations in the elderly are comprehensively known as immunosenescence . This ph T-cells  and impa T-cells -13, dysf T-cells -13, freq T-cells -23, skewtibodies -15.+, CD8+[+ T-cells, and a limited production of naïve cells. Additionally, the increased memory and activated effector CD8+ T-cells [In detail, overall diversity of the total T-cell repertoire is skewed by oligoclonal expansions of memory CD4+, CD8+-23 and C T-cells ,25 show  T-cells  and a li T-cells . They ar T-cells . Such exThere is also evidence of an increased concentration of IL-6, TNF-α, and various acute-phase proteins, suggesting that aging is associated with low-grade inflammatory phenotype -13,28,29Consequently, due to these alterations in the adaptive immune function, the elderly shows increased sensitivity to infectious diseases and cancer, and poor responses to vaccination ,33. DiffNaïve T-cells able to specifically recognize a particular antigen are usually very few. In order to efficiently respond to an antigenic stimulus, they are able to rapidly perform many cell divisions, producing multiple clones. Once the acute antigenic challenge is resolved, excess clones undergo apoptosis, and the organism retains a certain number of memory cells . If the is a term coined by Schreiber and colleagues to describe a process originating from the interaction between the host immune system and tumor cells -23.induced tolerance. Cancer originates from the transformation of the host cells: during this process, multiple accumulating mutations turn the "self" into a "non-self". This transformation is expected to trigger an immune response, but tumor immunity is different because of a number of possible mechanisms of immune evasion. The cancer cells often display weak immunogenicity, especially due to the lack or low expression of co-stimulatory molecules (such as B7) or inefficient antigen presentation ability. Therefore, potentially tumor-reactive T-cells could be induced to mount ineffective immune responses or even to present anergy.Although aimed to prevent auto-immunity, tolerance can be directed towards non-self antigens, following a process called immunoselection, represents the first cause of immune escape.At advanced stages of carcinogenesis, the immune system exerts a selective pressure on the genetically unstable tumor cells: those able to resist to or suppress the immune response are selected. This phenomenon, known as immunosubversion [Later in the process of tumor progression, inefficient immune responses can even favor tumor growth, in a process known as bversion .cancer immunoediting: effective recognition corresponds to the elimination of transformed cells, but tumor cell variants can survive this process and enter an equilibrium phase, followed by an uncontrolled tumor expansion termed escape.This complex sequence of events is known as It is evident that elimination , their shortening is thought to function as a "sensor" of cells age -23,40. PIn conclusion, cellular senescence is a genetically determined process that can also be induced by various alterations in the tumor environment. Studies on advanced cancer disease have rarely demonstrated the presence of senescent cellular phenotypes ,46. FurtNot only adaptive responses, but also innate immune system is dysregulated during the senescence. The term "inflammaging" has been coined in 2000 by Franceschi C. et al.  to descrThe association between chronic inflammation and cancer has been widely described in different organs: inflammatory bowel diseases (IBDs) determine an increased incidence of colorectal cancer, while chronic gastritis is associated with gastric adenocarcinoma, and chronic viral hepatitis often leads to liver cancer. Various mechanisms account for inflammation-related carcinogenesis Figure .1. inflammatory leukocytes generate reactive oxygen and nitrogen species , causing local tissue alterations and DNA damage2. enhanced proliferative signals mediated by cytokines released by inflammatory cells increase the risk of mutations3. alterations in epigenetic mechanisms alter gene expression patterns+ and CD8+ T-cell proliferation, to block NK cell activation, to limit DC maturation, and to polarize immunity towards a type-2 helper response4. inflammatory mediators affect suppressor cell populations, particularly MDSCs and T-regulatory (Treg) cells, able to inhibit CD45. the inflammatory microenvironment favors tumor-associated angiogenesis6. cytokines generate a preferential niche supporting cancer stem cells (e.g. IL-4 for colon carcinoma stem cells).In this scenario, where a number of alterations involve multiple cellular mechanisms, there is a growing need to identify one or a few target molecules shared by all cancer cells, in order to synthesize new and more efficient treatments. One of the mechanisms that could be targeted for this purpose is represented by telomere shortening/elongation.Telomeres maintain chromosomal stability through repeated cellular divisions. Their repeated sequence of non-coding DNA (TTAGGG) has the crucial function to preserve genomic information during cell replication, but it results in progressive telomere shortening. Once the limiting length is reached, signaling of chromosomal instability triggers cellular senescence and apoptosis, unless the cell has the ability to preserve telomere length.telomerase is a reverse transcriptase responsible for the maintenance of telomeres length. Since telomerase discovery in 1984 by C.W. Greider and E. Blackburn, it represented an attractive therapeutic target because of its role in aging and cancer. Telomerase has recently gained attention for its potential applications in cancer therapy, anti-aging research and treatment of chronic diseases.The enzyme cancer stem cells. Accordingly, telomerase has been found in a variety of human cancers (80-90%), a condition that satisfies the need for a tumor specific target and could define this enzyme as a hallmark of cancer disease because telomerase activity also is poorly or non-expressed in normal somatic cells.Telomerase expression makes cells potentially "immortal", including Different approaches have been tailored to telomerase synthesis or activity.1. Direct enzyme inhibition, through antagonists of different components of the macromolecular complex (such as hTERT or TERC)2. Active immunotherapy, aiming to stimulate immune responses against tumor cells expressing hTERT. For instance, Antigen-Presenting Cells (APCs) displaying hTERT epitopes, are able to stimulate specific T-cells to react towards telomerase-expressing tumors, also activating hTERT-specific memory T-cells3. Telomere disruption/alteration: blocking or altering telomere structure (e.g. by using mutant engineered forms of hTERC) may quickly induce a DNA damage response and consequent apoptosis. However, this approach could target telomeres in normal cells or G-rich chromosome regions, resulting in potentially lethal toxicities4. Delivery of telomerase promoter-controlled suicide genes, able to induce apoptosis selectively in telomerase-positive cells5. Blocking telomerase expression or functions would result in reduced enzyme activity in tumor cells. The potential disadvantage of these approaches is the need for prolonged therapies to maintain a clinical response.Geron Corporation™ http://www.geron.com, belongs to the class of direct telomerase inhibitors blocking the hTERC. GRN163 intracellular distribution has been recently improved by lipid conjugation [Examples of drugs recently under clinical trials are GRN163, GV1001 and GRNVAC1. The first, from jugation  (GRN163→+ and CD4+ T-cell responses. GV1001 is a hTERT peptide activating CD8+ T cells (through MHC class I). GRNVAC1 consists in autologous DCs transduced with TERT-LAMP encoding mRNA. LAMP  favours lysosomal processing and presentation on MHC class II).GV1001 (GemVax/Pharmexa™) and GRNVAC1 (Geron Corporation™) are two active immunotherapy options, both able to elicit CD8Adoptive vaccination seems the most promising strategy to improve cancer vaccines in the geriatric population. It consists of transferring immunity through the administration of specific antibodies or immune cells, such as T-cells -52 or DCHowever, even DC populations undergo important changes with advancing age.Lots of studies have been conducted on animal models and in humans, demonstrating the decrease of DCs in number, distribution, and potentially, their generation and development from hematopoietic precursors ,53,55-57In vitro studies found that DCs from young and old subjects expressed the same molecular patterns on their surface. Furthermore, DCs generated in vitro from elderly donors survived better under culture conditions. DCs from different healthy individuals were also equally effective with age in stimulating T cell responsiveness in vitro -54,58. HIn order to stimulate tumor-specific CTLs , DC vacc1. whole tumor lysates2. viral, bacterial or yeast vectors3. specific proteins/peptides4. nucleic acidsAutologous or allogenic tumor cells can be modified and administered in association with adjuvants or as tumor-cell lysates. The advantage of this method is the possibility that multiple and still unknown antigens can be simultaneously targeted. Moreover, whole tumor cell vaccines elicit MHC-I and -II responses. On the contrary, unfavorable aspects include a probability that unknown weak TAAs may trigger auto-immune responses.Vectors are the more immunogenic way to deliver recombinant genes into DCs, which are better than direct administration with adjuvants. Issues include the choice of an efficient vector, and a balance between the stimulation of innate versus adaptive responses.Proteins can be administered as single agents, in combinations, or as fusion proteins, and also peptides as single agents, agonist peptides, and anti-idiotype antibodies.+ CD8+ subsets leads to a less effective long-term anti-tumor immunity.Advantages include cost-effective production, storage, and distribution. The identification and administration of TSAs is more accurate, leading to a low risk of inducing auto-immunity respect to tumor cells. On the other hand, single proteins or peptides are weakly immunogenic, and tumor antigen mutations or loss can easily escape immune recognition. Another disadvantage is represented by HLA-restricted responses that limit their use to selected patients. Finally, their poor ability to induce balanced activation of CD4The consecutive administration of different TSAs, in different time points, has shown better outcomes than the simultaneous one.DNA-based vaccines are a strategy capable of activating strong immunity against weak TAAs. Approaches to enhance their potency include improved delivery systems, co-administration of cytokines, or the use of separate plasmids encoding non-self antigens; mRNA vaccines are based on transient transfection of non-dividing cells: the transfected mRNA does not integrate into the host genome , determiHowever, triggering the immune response alone seems to be an incomplete strategy of vaccination because of multiple cited factors harming the immune system.The heterogeneity of the elderly makes managing the older patient with cancer very challenging. Chronological age does not correlate with better response or increased toxicity to treatment. There are no known criteria to help decide management plan as older adults are underrepresented in oncology clinical trials that set the standard of care. The Comprehensive Geriatric assessment (CGA) has been suggested as a tool to evaluate elderly patients with cancer. It includes multidimensional assessments, including comorbidities, functional status, cognition, psychological state, nutrition, social conditions and medications. This provides a detailed assessment of the patient which helps to individualize management. Malnutrition and functional statuses were found to independently predict change in cancer management especially in the vulnerable elderly .The flow-chart highlights the different possibilities of treatment administration and association, focusing on cancer vaccination handiness, independently from disease staging and treatment purpose.When the risk of morbidity and mortality from neoplastic disease is low considering life expectancy and severity of co-morbidities, the choice should be palliation, including:• Management of co-morbidities• Symptomatic approaches (control of pain and cancer-related symptoms)• Supportive medical and psycho-social care.If the estimate of life expectancy and the assessment of co-morbidities and functional status determine a moderate to high risk of morbidity and mortality from cancer during the lifespan, then a complete clinical and psycho-social evaluation should be performed in order to estimate a realistic risk/benefit ratio Figure .Apart from the patient's underlying medical characteristics and the number of conditions affecting the immune system during cancer disease, the true risk factors for a cancer therapy are represented by its inefficacy and side effects Figure .If risk/benefit ratio is acceptable, conventional curative options include surgery, radiation therapy and chemotherapy, usually dose-adjusted Figures  and 5.Surgical approaches may represent the first option for solid tumors; elective surgery in the elderly cancer patients, and in the geriatric population in general ,73, haveBoth brachytherapy and external beam source can be proposed either in the curative or palliative setting. RT is usually effective and well tolerated. However standard protocols and/or doses sometimes need to be modified according to patient's conditions or to the onset of complications . As for Chemotherapy may be considered as a first-line approach, as well as an adjuvant in combination with RT, or as palliative treatment. In any case, it should always be individualized in the elderly. Clinical trials have focused mainly on young and adult populations, and in a few cases, on a selected, much healthier population of "young old" (65-75 years old) or "old" patients (76-85 years old). However, only a relatively small percentage of the geriatric population is actually fit and capable of tolerating standard dose CT regimens . The inc"Targeted therapies" represent a recent therapeutic pharmacological option for a number of malignancies, and are based on the concept that molecular changes responsible for malignant transformation can be targeted by specific agents. The aim of these treatments is to discriminate cancer cells, reducing adverse effects on healthy cells and improving overall benefits. This option captured increasing interest in geriatric cancer patients' care, yet beneficial and adverse effects should be further analyzed in this segment of the population, also for those patients who are unable to tolerate cytoreductive CT. Once more, cancer vaccination could be associated with this option or also administered alone in this group of patients.However, inclusion of the elderly  in cancer vaccine clinical trials is warranted, and a careful selection of patients who would benefit from this treatment is critical ,44,55-57Cancer prevention remains critical in the geriatric, as well as in the young population ,44,55-57The development and use of cancer vaccines also should be widely encouraged ,44,55-57CGA: Comprehensive Geriatric Assessment; IBD: Inflammatory Bowel Disease; MDSC: Myeloid-Derived Suppressor Cell; QOL: quality of life; TAA: Tumor-Associated Antigen; TCR: T-Cell Receptor; TSA: Tumor-Specific Antigen; TNF: Tumor Necrosis Factor.The authors declare that they have no competing interests.PM, LM, SR, MCI and EC reviewed the current literature. PM wrote the manuscript and MCI, GA, SR, LM, EC, MJ revised the manuscript. MCI conceived and drafted the manuscript. MCI, EC, GA approved the final version.


Near-shore coral reef systems are experiencing increased sediment supply due to conversion of forests to other land uses. Counteracting increased sediment loads requires an understanding of the relationship between forest cover and sediment supply, and how this relationship might change in the future. Here we study this relationship by simulating river flow and sediment supply in four watersheds that are adjacent to Madagascar’s major coral reef ecosystems for a range of future climate change projections and land-use change scenarios. We show that by 2090, all four watersheds are predicted to experience temperature increases and/or precipitation declines that, when combined, result in decreases in river flow and sediment load. However, these climate change-driven declines are outweighed by the impact of deforestation. Consequently, our analyses suggest that regional land-use management is more important than mediating climate change for influencing sedimentation of Malagasy coral reefs. Forest cover up-river influences the sediments reaching coral reefs, but how this relationship is affected by future climate change is not clear. In a study of the Malagasy coral reefs, Maina et al. find that regional land-use management is more important than mediating climate change for reducing reef sedimentation. Madagascar is a global biodiversity hotspot and is therefore of high conservation priority1315689Pronounced climate change and LULCC represent the two primary challenges that most ecosystems will face this century1315-ecological system dynamics in Madagascar and throughout the tropics18Using a hydrological and sedimentation modeling framework developed for Madagascaret al.et al.To determine the relative influence of climate change on sedimentation, we derived projected multi-model ensemble mean changes in precipitation and temperature from six GCMs, in which three Intergovernmental Panel on Climate Change (IPPC) emission scenarios Climate-mediated changes in precipitation and temperature have variable effects on river flow between regions and scenarios . The souTo determine the influence of LULCC on sedimentation, we constructed different possible land-use inputs for the hydrological models (Methods). These configurations were based on present-day land-use (2000), undisturbed natural forest based on bio-climate zones4The impacts of LULCC on sediment yields demonstrate the profound influence of human actions on tropical hydrologySimulated changes in sediment yield when plotted against change in forest cover for each region indicates regionally specific trajectories owing to the bio-climatic differences and the disproportionate effects of forest manipulation policies on forest cover . SedimenThe NE is one of the most hydrologically sensitive watersheds, where small changes in forest cover are projected to produce large changes in sediment yield. The NE region is still covered by relatively large areas of low-lying tropical forests, albeit fragmented, as a result of a low population density2  and sediment yield (tonnes per year)We used two existing models (STREAMx–y points in the watershed(s) being simulated, or as spatial maps of river flow per time step. N-SPECTWe used the STREAM -distributed hydrological model to simulate monthly river flowhttp://www-pcmdi.llnl.gov/projects/cmip/index.php). Finally, we applied a change-over-or time or delta-methodThe STREAM model is calibratedTo investigate the relative influence of forest cover on hydrology, we constructed nine LULCC scenarios as follows: (i) present-day land use, based on a land-use map for year 2000, which was developed from multi-temporal 1998–2001 satellite dataFor the afforestation and deforestation of cells, suitability for each scenario was computed for each cell, based on the slope and proximity to roads. For the 10% deforestation scenario, 10% of the forested cells with the highest suitability for deforestation (low slope and short distance to roads) in the whole of Madagascar were deforested. Note that this means that deforestation percentages in the four catchments considered in this study are therefore not necessarily the same as Madagascar as a whole. For afforestation, the reverse has been done. The 10%  of the non-forest cells with the highest suitability to be forest  were transformed into forest cells. Again, as the 10% afforestation scenario refers to 10% in the whole of Madagascar, percentages in the individual catchments may differ. STREAM utilizes crop factors maps , for determining potential and actual evapotranspirationRainfall erosivity is a measure for the erosive force of rainfall, and is a required input of RUSLE-based models including N-SPECT. Often, the large-scale mapping in data-poor regions is based on interpolation of erosivity values derived from rain-gauge dataSoil data was downloaded from Version 1.1 of the Harmonized soil database of the world (FAO/IIASA/ISRIC/ISSCAS/JRC 2009). STREAM utilizes the water-holding capacity of the soil as one of the input variables. The soil database was used in a reclassification procedure to develop the water-holding capacity map for input in STREAMS) and slope length (L) that are derived from DEM are RUSLE parameters that adjusts erosion rates based on topography, assigning higher rates to longer or steeper slopes and lower rates to shorter or flatter onesSTREAM utilizes the flow direction map and the digital elevation model (DEM) maps as inputs. Hydrologically corrected DEM at 500 m resolution maps were downloaded from hydroSHEDS’s website3 s-1 for selected locations, which included outlets points of rivers, which drain each of the four regions (http://daac.ornl.gov/RIVDIS/rivdis.shtml)STREAM model was developed using present-day climate and land-use for the entire island regions . ObserveN-SPECT tool was run for each year from 1975–2006, with annual MFI, precipitation, land cover (crop factors), DEM and soil as the input variables. This provided with among other outputs, annual sediment yield per unit area in metric tonnes per year. To estimate sediment under GCM scenarios, relationships between present-day river flow (STREAM output) and present-day sediment load were established using bivariate regressions. River flow was summarized for each year  and regressions performed between each of these statistics and present-day sediment output. Annual maximum average river flow was found to have a better fit with annual sediment yield than with annual averages and annual minimum. The relationships found were then applied to estimate corresponding future sediment.J.Z, J.M., H.dM. and J.V. designed the study. J.M., H.dM., J.S.M. and J.V. generated model outputs and conceived data interpretation. J.S.M. and T.M. contributed to design of land-use scenarios and choice of key study areas. TRM was supported by the John D. and Catherine T. MacArthur Foundation. All co-authors contributed to manuscript writing, performed model interpretations and discussions of the model scenario implications.How to cite this article: Maina, J. et al. Human deforestation outweighs future climate change impacts of sedimentation on coral reefs. Nat. Commun. 4:1986 doi: 10.1038/ncomms2986 (2013).


To the Editor: Rad and colleagues recently described variation in some genes involved in DNA repair  in Mycobacterium tuberculosis strains of different genotypes  rate in rpoB526 or rpsL43 under counterselection by streptomycin or rifampin, respectively  were not found in its genome  circumstances through inactivation or down-regulation of some mutT genes. Further, the two most frequently described rpoB mutations are 531TCG→TTG and 526CAC→TAC. Both are cytosine-to-tymine transitions, which easily occur by spontaneous cytosine deamination to uracil. Indeed, M. tuberculosis is a G+C rich organism, therefore, it is naturally at high risk for cytosine deamination. Furthermore, pathogenic mycobacteria are at increased risk for deamination because of the production of reactive oxygen and nitrogen intermediates inside host macrophages. This deamination process is normally counteracted by uracil-N-glycosylase, the product of the ung gene, and organisms defective in the removal of uracil from DNA have an increased spontaneous mutation rate and more G:C→ A:T base-pair transitions  is present in the genome of M. tuberculosis. In the E. coli in vitro model, a translesion synthesis enzyme (dinB encoded DNA polymerase IV) activity clearly promoted more important frameshift mutations (single-base deletions) in two thirds of the spontaneous mutants (I propose an explanation of these observations in terms of second-order selection of hypermutable (mutator) alleles based on alterations in DNA repair genes. Unlike that of other antituberculosis drugs, resistance to rifampin is acquired in most utT gene ,6; the Mnsitions . Merchanmination . On the mediates . In summl strain . In cont mutants .rpoB mutations in M. tuberculosis have been hypothesized to arise as a compensatory mechanism to ameliorate the fitness costs of the original resistance mutation by a secondary mutation , exhibi


TPA) gene polymorphisms with ischemic stroke, but the results were contradictory. We aimed to explore the role of TPA -7351C/T SNP in the susceptibility to ischemic stroke through a meta-analysis.A number of studies assessed the association of tissue plasminogen activator with 95% confidence intervals (CIs) were used to assess the strength of associations. Stroke subtype was determined using Trial of Org 10172 in Acute Treatment criteria (TOAST). Statistical analyses were performed using the STATA12.0 software.A total of 2,299 ischemic stroke cases and 1,948 controls in seven case-control studies were included in the meta-analysis. Significant association between -7351C/T polymorphism in the TPA gene and ischemic stroke was observed in all comparison models . In the subgroup analysis by ethnicity, TT homozygote carriers had a 142% increased risk of ischemic stroke compared with the C allele carriers among East-Asians , but not in South-Asians and Caucasians, and significantly increased risks were found for T versus C among both East-Asians  and Caucasians. Further stratification for stroke subtype in three Caucasian studies showed the association between -7351C/T polymorphism and Large-artery atherosclerosis (LAA), but not Small-vessel occlusion (SVO) and Cardioembolism (CE).TPA gene would be a risk factor for ischemic stroke, especially among East-Asians compared with Caucasians, but not in South-Asians, and it may play a role in the pathogenesis of LAA in Caucasians, but not in SVO and CE.This meta-analysis suggested that the -7351C/T polymorphism in  The coagulation system and fibrinolysis system maintain a dynamic equilibrium under normal conditions. When pathologic processes overwhelm the regulatory mechanisms, excessive quantities of thrombin form, initiating thrombosis TPA gene was first identified in 2000 and shown to be associated with the TPA release rates TPA and ischemic stroke showed contradictory results. Jannes et al. found the TT genotype was significantly associated with ischemic stroke in Australian population . Stratification for stroke subtype showed the association between the polymorphism and lacunar infarction, but not other subtypes Endothelium-derived tissue plasminogen activator (TPA) is the primary mediator of local intravascular fibrinolysis TPA’ and ‘polymorphism’ OR ‘variant’. The search was performed without any restriction on language. Two investigators (X Sun and R Lai) independently reviewed study eligibility and reached a consensus on which studies to include for review. We also checked the reference of selected articles for any further relevant studies The PubMed, MEDLINE, EMBASE, China Biological Medicine Database and WANFANG DATA databases were searched for publications until August 2012 using the following terms: ‘ischemic stroke’ OR ‘cerebral infarction’ OR ‘cerebrovascular disease’ OR ‘stroke’ in combination with ‘tissue plasminogen activator’ or ‘TPA -7351C/T and ischemic stroke, b) ischemic stroke was confirmed by neuroimaging data (magnetic resonance imaging or computer tomography), c) containing useful genotype frequencies, d) the genotype distribution of controls in Hardy-Weinberg equilibrium (HWE).The selected studies had to be in accordance with the following major criteria: a) well-designed case-control studies to evaluate the association between Studies were excluded if one of the following existed: a) patients younger than 18 years old, b) the genotype frequencies or number not reported, c) animal studies, reviews, case reports, abstracts and family-based studies. For duplicate or overlapped publications, we choose the largest sample size or the most recent one.The following information was extracted from the selected studies by two independent investigators, any discrepancy was resolved by discussion or a third author (Li): first authors, publication year, country in which the study was conducted, characteristics of cases and controls , number of genotypes and total number of cases and controls.TPA -7351C/T gene polymorphism and risk of ischemic stroke was assessed by pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs). The pooled ORs were performed for dominant model (TT+CT versus CC), recessive model (TT versus CT+CC), and additive model (T versus C) respectively. Stratified analyses were also performed by ethnicity and subtypes of ischemic stroke according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. The presence of heterogeneity was calculated by the Chi-square-based Q-test. If the P>0.1 of the Q-test which indicated heterogeneity was not observed among the studies, the fixed-effects model (Mantel-Haenszel method) was used to calculate the pooled ORs. Otherwise, the random-effects model was adopted. The Z test was used to determine the pooled OR with the significance set at P<0.05. Publication bias was tested by Begg’s funnel plot P<0.05 level. Sensitivity analysis was performed by sequentially excluding individual study to assess the stability of the results. HWE was tested by Pearson’s X2 test (P<0.05 means deviated from HWE). STATA 12.0 software was used to perform all statistical analyses .The strength of the association between TPA and ischemic stroke, two were conducted in East-Asians, one in South-Asians and four in Caucasians. In addition, three of four Caucasian studies reported ischemic stroke subtypes information according to the TOAST classification A total of fifty-seven papers were obtained by the literature search, among which seven fit the inclusion criteria TPA -7351C/T polymorphism was significantly associated with ischemic stroke in all comparison models . However, in the stratified analysis by ethnicity, significantly increased risk of ischemic stroke was found among East-Asians in recessive model  (As shown in 07–5.48)  and addi07–5.48) , but notTPA -7351C/T and ischemic stroke risk were observed in all genetic models of LAA, SVO and CE, except for the recessive model    and addi00–2.59)  in LAA.P values were 0.072 in Begg’s test and 0.262 in Egger’s test, separately, also suggesting no obvious publication bias.A single study involved in the meta-analysis was deleted each time, statistically. Similar results were obtained, indicating high stability of this meta-analysis (data not shown). Publication bias was assayed by the Begg’s funnel plot and Egger’s test. The shape of the funnel plots was seemed symmetrical in recessive model (TT vs. CT+CC) . Then, PIschemic stroke is a heterogeneous disease, which is affected by a number of genetic mutations and environmental factors. Previous data suggest that fibrinolytic pathways have been involved in stroke pathogenesis TPA gene shown to be strongly correlated with endothelial TPA release rates and less than half the release rate was observed in the TT homozygous as compared with the CC homozygous TPA release rates may increase the susceptibility of ischemic stroke. Genetic factors play an important role in the variance of endothelial TPA release TPA gene and ischemic stroke risk, including 2,299 ischemic stroke cases and 1,948 controls. We found that carriers of the TT homozygote was associated with significant increased risk of ischemic stroke among East-Asians,but not in South-Asians and Caucasians. Then T allele had a 33% increased risk of ischemic stroke in East-Asians and 16% in Caucasians. It is possible that different genetic backgrounds and the environment they live in may account for these differences This meta-analysis of 7 case-control studies systematically evaluated the association between -7351C/T polymorphism in the TPA gene. Thus, analyzing the relationship between TPA genotypes and subtypes of ischemia stroke risk is an excellent perspective to better characterize the associations between genes and ischemic stroke from the standpoint of pathogenesis. Stratified analyses performed by subtypes of ischemic stroke in Caucasians indicated that a statistically significant finding between TPA -7351C/T polymorphisms and ischemic stroke risk was only witnessed in LAA but not in SVO and CE. However, Jannes et al. Stroke subtype in three Caucasian studies was determined using TOAST classification system, the common system for categorization of subtypes of ischemic stroke mainly based on etiology, which affects prognosis, outcome, and management Some limitations of this meta-analysis should be considered. First, given that only seven published studies were included in the meta-analysis, publication bias could potentially occur, even though we sought to find as many publications or unpublished studies as we could by means of various searching approaches, evaluated the quality of literature strictly and used explicit methods for statistical analysis to minimize the publication bias and heterogeneity, and no statistically significant publication bias was noted in our meta-analysis. Second, the stratified analyses by subtypes of ischemic stroke were only performed in three Caucasians, owing to the insufficiency information which was impossible to obtain from some studies. Third, the number of cases and controls involved in the meta-analysis was still limited, studies with larger sample size and high quality are needed to validate our results in future. Finally, the case-control studies belong to retrospective research that is subject to methodological deficiencies.TPA -7351C/T polymorphism was associated with increased risk of ischemic stroke, especially among East-Asians compared with Caucasians, but not in South-Asians. Further stratification for stroke subtype in Caucasians showed the association between the polymorphism and LAA, but not SVO and CE. Larger and well-designed multicentric studies are still needed to be conducted in future among different ethnicities.In conclusion, this meta-analysis suggested that the Figure S1Prisma 2009 Checklist.(DOC)Click here for additional data file.


Interestingly, the majority of food allergen epitopes were B-cells epitopes whereas a fairly even number of B- and T-cell epitopes were defined for airborne allergens. In addition, epitopes from nonhumans hosts were mostly T-cell epitopes. Overall, coverage of known allergens is sparse with data available for only ~17% of all allergens listed by the IUIS database. Thus, further research would be required to provide a more balanced representation across different allergen categories. Furthermore, inclusion of nonpeptidic epitopes in the IEDB also allows for inventory and analysis of immunological data associated with drug and contact allergen epitopes. Finally, our analysis also underscores that only a handful of epitopes have thus far been investigated for their immunotherapeutic potential.Adaptive immune responses associated with allergic reactions recognize antigens from a broad spectrum of plants and animals. Herein a meta-analysis was performed on allergy-related data from the immune epitope database (IEDB) to provide a current inventory and highlight knowledge gaps and areas for future work. The analysis identified over 4,500 allergy-related epitopes derived from 270 different allergens. Overall, the distribution of the data followed expectations based on the nature of allergic responses. Namely, the majority of epitopes were defined for B cells/antibodies and IgE-mediated reactivity, and relatively fewer T-cell epitopes, mostly CD4 It is estimated that 50 million people in the US are affected by airborne allergens, including approximately 35 million affected by upper respiratory allergies  , and 16 Allergome, which provides information on allergenic molecules causing IgE-mediated disease, and Allergen.org, which is the official site for the systematic allergen nomenclature approved by the World Health Organization and International Union of Immunological Societies (WHO/IUIS) Allergen Nomenclature Sub-committee]. However, until recently, a resource describing the actual epitopes (defined as the molecular structures coming in contact with antibodies or T-cell receptors), and the immunological events associate with epitope recognition, was not available. The immunological basis of allergy-related disease is universally recognized. At the level of adaptive immunity, the recognition of specific allergens by antibodies and T cells plays major roles both as effectors and regulators of allergic diseases. Several bioinformatics resources, cataloging and describing allergen protein sequences, are available to the scientific community such as the http://www.immuneepitope.org/). It contains data curated from published literature, -submitted by the NIAID's high-throughput epitope discovery projects, and imported from other databases. The database contains antibody and T-cell data for human, nonhuman primate, and rodent hosts, as well as a number of other animal species, and targets epitopes associated with infectious diseases, autoimmunity, transplantation, and allergy. Data related to both peptidic and non-peptidic epitopes are curated within the IEDB.The immune epitope database (IEDB) was created, to provide the scientific community with a repository of freely accessible immune epitope data  hosts. To identify within the IEDB the subset of data which is allergy related, we followed the process described in more detail by Davies et al. . More sp The allergy-related epitopes represent both peptidic as well as non-peptidic structures from a wide range of sources, including pollens, dust mites, molds, dander and foods, nonprotein moieties of plants (carbohydrates), as well as drugs, haptens, metals, and chemical substances from occupational exposures. The curated data was obtained using a variety of different assays, such as ELISA, Western blot, proliferation assays, surface plasmon resonance (SPR), radio immunoassay (RIA), and X-ray crystallography, and describes epitope-related reactivity such as histamine release, hypersensitivity (PCA), delayed-type hypersensitivity (DTH), and immunotherapy assays. http://tools.immuneepitope.org/wiki/index.php/Main_Page. For the purpose of this report, the total number of epitopes reported in each case represents the total number of unique molecular structures experimentally shown to react with a B- cell or T-cell receptor (no predictions included). The IEDB captures these structures as they are defined in the literature and thus includes data describing structures categorized as minimal/optimal epitopes (11–15 resides), larger less well-defined regions (20–50 residues), and key residues identified as being involved in binding (1-2 residues). All of the data described herein were captured directly from the peer-reviewed literature (PubMed) by Ph.D. level scientists or through direct submission to the IEDB by research groups. Antibody and T-cell epitope definitions (length and mass restrictions) as well as IEDB inclusion criteria can be found at The entirety of the allergy-related data identified as described above was first inventoried to identify the total number of structures (positive and negative epitopes), their chemical nature (peptidic or non-peptidic), the total number of antibody/B-cell versus T-cell epitopes, as well as the effector cell phenotype or antibody isotype, and finally the total number of peer-reviewed references from which the data were derived. The second step involved investigating the distribution of epitopes among hosts: those epitopes defined in humans versus those identified using nonhuman animal models of allergy. In each case, the inventory of epitopes per host species included a breakdown according to reactivity: B cell  or T cell .allergen and genus species of the organism from which the epitope was derived. These main categories were then further parsed into subcategories on the basis of taxonomic origins  and included a subcategory for the most commonly encountered species in that main category.Following the initial inventory, the data were categorized according to the following established allergy categories: food, airborne (respiratory), contact, drug, and allergies to biting insects. This categorization was based on the The individual compounds representing drugs/pharmaceuticals were parsed into 21 subcategories on the basis of its chemical type  or by the way the compound is used to treat a particular condition . Contact allergen data were also further parsed into subcategories based on their species of origin (plants), chemical type , or mode of exposure . http://www.immuneepitope.org/) was stored in a MySQL database. The use of MySQL allows for the tailoring of database schema to the specific analysis and to keep the data synchronized with updates of the IEDB data production database. Data were periodically checked against the IEDB webpage using simple or advanced query interfaces for consistency and accuracy. Results from each query were exported as Excel files and further analyzed in that format. Tables and figures were generated from Excel. Data exclusions included structures for which only MHC binding data were available, as well as those instances in which the epitope was simultaneously used as both immunogen and assay antigen. The allergy-related data extracted from the IEDB  provides a response summary for all epitope data.A relatively smaller number of T-cell epitopes have been identified  . Of the The host distribution of epitopes can be found in Arachis hypogaea) allergens which comprise nearly 40% of the total plant allergen epitopes. Epitopes described for food allergens derived from animals fall into six taxonomic categories. These include mammals , bony fish (cod), bird (chicken eggs), mollusks , crustaceans (shrimp and prawns), and nematodes (fish meat parasite). By far, the largest number of epitopes has been identified for allergens related to cow's milk allergy, followed by epitopes defined from eggs, representing 70% and 20% of the total, respectively. Non-peptidic food epitopes reported to date are comprised of carbohydrates derived from peanuts, sugar beets, celery, and sea squirt . These include both peptidic and non-peptidic determinants derived from both plants and animals. The data have been parsed into three broad categories; most common food allergen sources, other plant, and other animal species . Peanut According to the CDC , allergeEpitopes defined for aeroallergens represent the second largest group within the IEDB, accounting for 40% of the records, including peptidic and non-peptidic determinants derived from plants, animals, fungal allergens, and some industrial chemical agents. Here, the data was parsed into the categories of most common airborne sources, other plant, fungal, and animal species . EpitopeAspergillus species dominate (70%). Finally, epitopes derived from aeroallergens from animals fall into three broad taxonomic categories: insects (cockroach and midge), arachnids , and mammals . Among the insects, epitopes derived from the midge are the most numerous, and within the Arachnid class, European house dust mites are the most heavily studied. In the taxonomic grouping representing fungi, which includes yeasts and molds, epitopes identified in antigens from α-L-Fuc-(1->3)-[α-D-Man-(1->3)-[α-D-Man-(1->6)]-[β-D-Xyl-(1->2)]-β-D-Man-(1->4)-β-D-GlcNAc-(1->4)]-D-GlcNAc from cedar pollen, D-glucopyranuronic acid from the fungus Trichosporon cutaneum, and mono-β-arabinofuranose from mugwort pollen. In addition, a number of non-peptidic chemicals were identified, including compounds causing respiratory symptoms following occupational exposure; toluene 2,4-diisocyanate (TDI), toluene meta-diisocyanate, 4-tolyl isocyanate, diphenylmethane-4,4′-diisocyanate, hexamethylene diisocyanate, phenyl isocyanate, phthalic anhydride, and trimellityl group (data not shown).Three non-peptidic determinants were described . These included Here again, the epitope data reflects the overall trends related to airborne allergy. Grass, tree, and weed pollen epitopes represent the majority of the data (~60%), followed by pet dander and house dust mite allergens. These findings are consistent with the overall prevalence of hay fever and/or allergic rhinitis in the general population, affecting some 18 million people annually . PerhapsApis mellifera), bald-faced hornets (Dolichovespula maculate), black-bellied hornets , common wasps (Vespula vulgaris), and ants (Myrmecia pilosula). Of these, epitopes derived from honeybees represent the largest portion, followed by wasps and bald-faced hornets. Surprisingly, only 2 B-cell epitopes for ant venom, 1 B-cell epitope for Black-faced hornets, and no antibody determinants for wasp venom were defined. There are also two non-peptidic determinants for antibody reactivity to honey bee venom. These include α-1,3-fucose and an N(4)-[α-L-fucosyl-(1->3)-N-acetyl-4-O-glycosyl-D-glucosaminyl]-L-asparagine residue . To date, the IEDB contains 125 antibody and T-cell epitopes related to the venom of stinging insects .These inThe IEDB currently contains curated data relating to immunological reactions to more than 90 different drugs associated with allergic disease. In most cases, the authors do not identify the exact reactive moiety of these non-peptidic chemical entities because the assays are carried out using the intact drug. These drugs can be further classified into 21 categories based primarily on biological function and structure . These i+/class II phenotype.Thus far, more than 80 contact allergens have been captured by the IEDB, as summarized in non-peptidic entities such as metals, industrial chemicals encountered by way of occupational exposure, and model haptens. A total of seven different metals described as associated with allergic contact dermatitis include beryllium , chromium (chromium trichloride), cobalt , copper , nickel  palladium , and zinc chloride. Of these, no single metal entity stands predominates, and as a group metals comprise only 7% of the contact allergens. Beryllium, chromium, zinc chloride, and cobalt are most often encountered in the industrial/manufacturing setting, whereas nickel, copper, and palladium allergies are most frequently associated with jewelry. Furthermore, the IEDB contains curated data relating to more than 70 compounds utilized in the manufacture of cosmetics, dyes, and certain constituents of manufacturing. A very large number of curated assays relate to model haptens, which include skin sensitizers such as trinitrophenyl (TNP), dinitrophenyl (DNP), 1-fluoro-2,4-dinitrobenzene (DNFB), and dinitrochlorobenzene (DNCB). These compounds have been used classically to define mechanisms of type IV contact hypersensitivity. Of these, DNCB appears to have received the greatest focus. A detailed list of all contact allergens can be found in supplemental Table 1. Three additional categories of contact allergens include As a further evaluation, we determined the relative epitope distribution by allergen for each source species (supplementary Tables 2–5). The total number of epitopes described per allergen varies greatly, and well-known allergens  tended to have greater numbers of defined epitopes compared to other allergens from the same organism . Similarly, the total number of T-cell versus B-cell epitopes varied greatly, with the vast majority of allergens heavily weighted toward one or the other phenotype and few having a relative balance of defined B and T epitopes (data not shown). Allergen.org resource, the official site for the systematic allergen nomenclature (Linnean system) that is approved by the World Health Organization and International Union of Immunological Societies (WHO/IUIS) Allergen Nomenclature Sub-committee. This site maintains a list of all currently known (described) allergens derived from plant, animal, and fungal species. We found that total number of allergens from which epitope data have been described varies from one allergen source to another. In some instances, epitope data is comprehensive, showing epitope data for all allergens identified by the IUIS list for a given species . However in other cases, allergen distribution is low, showing only a few of the known allergens , whereas other species have intermediate distribution   . FurtherIsolated epitopes can be utilized to induce or modulate allergic reactions in animal models. The use of synthetic epitopes to modulate allergic reactions has also been proposed and tested in a limited number of clinical trials , 18. Indin vivo for their ability to decrease allergic reactivity in vivo (as measure by the reduction of symptoms) and for those that were shown to decrease in vitro markers of allergic disease. This is done by selecting all B-cell or T-cell contexts designated in the IEDB as assay type equals “Reduction of Disease after Treatment” (B cell) or “Treatment” (T cell). Here, the assay type assigned by the IEDB indicates the nature of the immune response, and the details of the type of assay used  can be found within the curated data from the assay comments field. in vivo or on markers of disease as measured in vitro. To inventory which epitopes had been tested in these settings, we queried for antibody and T-cell epitopes that were tested either The analysis presented herein identified over 4,500 allergy-related epitopes derived from 270 different allergens. Protein allergens were categorized according to their source organism, which included plants, animals, insects, parasites, and fungi. Non-peptidic allergens were categorized into four groups including drugs and biologicals, industrial compounds, or those related to occupational exposure, metals, model haptens, and carbohydrates from plants.+/class II, with very few being defined for CD8+/class I). Likewise, most of the records related to the study of allergic reactions in humans, and fewer epitopes defined for mice and occasional epitopes defined for other hosts such as monkeys, pigs, dogs, rabbits, guinea pigs, and rats. The majority of peptidic epitopes were defined for foods  and plants (tree and grass pollens), while the majority of non-peptidic epitopes defined for drugs and biologicals (antibiotics). Overall, the distribution of the data follows expectations based on the nature of adaptive responses involved in allergy. Namely, the vast majority of allergy epitopes were defined for B cells/antibodies , and relatively fewer T-cell epitopes  of the known allergens have epitope-related data , while other species have epitope data from only a small number of known allergens .http://www.ebi.ac.uk/chebi/) database will further enable the scientific community to quickly retrieve and analyze the immunological data associated with these important classes of allergens. The recent completion of curation of non-peptidic allergy-related epitopes in the IEDB allows a first time inventory and assessment of important drug and contact allergens. The integration within the IEDB of representation and search capabilities based on the chemical entity of biological interest (ChEBI) (Finally, our analysis also inventoried which epitopes have been used to actively induce allergic disease in animal models or to modulate disease. Only a handful of epitopes have been investigated for their immunotherapeutic potential. If the promising results from human clinical trials were to be verified in later phase trails, we anticipate that the data cataloged within the IEDB might provide a wealth of leads for therapeutic intervention regimens. Supplementary materials contain the following:Supplemental Figure 1: Overall response summary.Supplementary Table 1: Contact allergens.Supplementary Table 2: Epitope distribution in different food allergens.Supplementary Table 3: Epitope distribution in different airborne allergens.Supplementary Table 4: Epitope distribution among stinging insects.Supplementary Table 5: Epitope distribution for latex allergens.Supplementary Table 6: Carbohydrate epitopes associated with allergic reactions.Click here for additional data file.Click here for additional data file.Click here for additional data file.Click here for additional data file.Click here for additional data file.Click here for additional data file.Click here for additional data file.


Sex-stratified multiple regressions and logistic regressions were conducted. Among women, CES-D scores correlated positively with systolic blood pressure and waist-to-hip ratio (P's < .05), but inversely with high-density lipoprotein cholesterol (HDL-C) (P < .01). Women had twice the odds for metabolic syndrome if CES-D scores ≥16 and had a ≥14% increase in odds of hypertension, abdominal obesity, and low HDL-C with each 5-unit increase in CES-D scores. Among men, CES-D scores correlated positively with high-sensitivity C-reactive protein (P < .05), and odds of hypertension increased by 21% with each 5-unit increase in CES-D scores. Depressive symptoms may promote premature CVD risk in African Americans, at least in part, via CVD risk factors and prevalent metabolic syndrome, particularly in African American women.Young to middle-aged women usually have notably lower rates of cardiovascular disease (CVD) than their male counterparts, but African American women lack this advantage. Their elevated CVD may be influenced by sex differences in associations between depressed mood and CVD risk factors. This cross-sectional study examined whether relations between scores on the Center for Epidemiologic Studies-Depression (CES-D) scale and a spectrum of CVD risk factors varied by sex among African Americans ( Young to middle-aged African American women have elevated rates of premature cardiovascular morbidity and mortality , 2, inclDepressed mood has been linked to CVD risk factors and to metabolic syndrome –37, withAccordingly, this study aims to addresses gaps in the literature by cross-sectionally examining how depressive symptoms relate to select CVD risk factors—blood pressure, fasting lipid and glucose levels, waist-hip ratio (WHR), and hsCRP—in young-to middle-aged African American women and men. Both continuous outcome measures  and traditional clinical cut-offs  were examined. Prevalent metabolic syndrome also was assessed.The sample includes 1,076 African American men and women, ages 30 to 64 years, who participated in the first wave  of the larger Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study. HANDLS is an ongoing 20-year epidemiological study of health disparities in Baltimore, Maryland initiated in 2004 by the National Institute on Aging Intramural Research Program at the National Institutes of Health. As reported previously , its basThe HANDLS study procedures have been described in detail previously . To summCES-D: the 20-item CES-D scale assesses the frequency of depressive symptoms experienced in the past week on a 4-point Likert scale ranging from “0” (“rarely or none of the time (less than one day”) to “3”  . Scores Blood pressure/hypertension: systolic and diastolic blood pressure rates (SBP and DBP) were measured twice using the brachial artery auscultation method after seated participants rested with legs uncrossed for 5 minutes. The two readings (one reading from each arm) were averaged for the analyses. Hypertension was defined as average SBP ≥140 mmHg or DBP ≥90 mmHg or prior diagnosis of hypertension  or use of antihypertensive medication (per participants' pharmacy bottles) [Waist-Hip Ratio/Abdominal Obesity. Waist-hip ratio (WHR) was calculated as the waist circumference divided by the hip circumference. Waist circumference was measured with a tape measure placed at the midpoint between the lower rib margin and iliac crest. Hip circumference was measured at the widest point of hips and buttocks. Abdominal obesity was defined as WHR ≥0.90 in men and ≥0.85 in women [in women .Lipids/Dyslipidemia, Glucose/Diabetes, and hsCRP/High Inflammation. After an overnight fast, blood samples were obtained and standard laboratory methods  were used to assess total serum cholesterol (CHOL), low- and high-density lipoprotein cholesterol , triglycerides (TG), glucose (GLU), and hsCRP. Dyslipidemia subtypes were defined as high CHOL (>240 mg/dL), low HDL-C (<40 mg/dL in men or <50 mg/dL in women), high LDL-C (>160 mg/dL), or high TG (>200 mg/dL) [h LDL-C >60 mg/dL,h LDL-C >60 mg/dL,0 mg/dL) .Metabolic Syndrome. The criteria recommended by the National Cholesterol Education Program (NCEP) Adult Treatment Panel III [anel III  were useanel III .Sociodemographic: data were collected on age, sex, and poverty status during the home interview. Poverty was defined as family income <125% of the Federal poverty threshold . Lifestyle: self-reported medical histories were the data source for covariates of lifetime smoking history , lifetime drug history , and past week use of alcohol . 2). Self reported medical histories were the source of data on prior diagnoses of hypertension/CVD, diabetes, and menopause status . Staff recorded prescriptions, which were subsequently aggregated into antihypertensive, antidiabetes, antidepressant, cholesterol-reduction, and hormone replacement therapy medications based on self-reported use or based on pharmacy bottles participants brought to their examinations. Biomedical: BMI was calculated as weight in kilograms divided by height in meters squared  and as clinical cut-offs (in logistic regressions). Descriptive analyses and P < .05) with the outcome variables. Covariates were omitted from certain models when the outcome variable was similar to the covariate .For multiple regression models, the outcome variables were SBP, DBP, WHR, CHOL, HDL-C, LDL-C, TG, GLU, and hsCRP, whereas the outcomes in logistic regression models were hypertension, high WHR, hypercholesterolemia, low HDL-C, high LDL-C, high TG, diabetes, and high hsCRP. In both sets of analyses, a standard set of covariates was entered in the first step/block, and CES-D scores (continuous) were entered as the primary predictor variable in the last step/block. , we divided the original CES-D scores by 5 and used these modified continuous CES-D scores in the logistic regressions; thus, the ORs shown for CVD risk factors are for every 5-point increase in CES-D scores.) The covariates were age, poverty status, and BMI; histories of CVD, hypertension, and diabetes; medications ; hormone replacement therapy and menopause status (women only); and history of smoking, drug use, and recent alcohol use. Selection of covariates was based on prior literature –26, 44 oSecondary analyses utilized logistic regression to examine whether clinically significant depression symptoms  were associated with increased odds of meeting criteria for metabolic syndrome . Logistin's ranged from 491 to 592). Consequently, sample sizes were reduced in all analyses involving these measures, as well as metabolic syndrome. While the overall sample included 1,076 adults, data on fasting CHOL, HDL-C, LDL-C, TG, GLU, and hsCRP were available only for a subset (P < .05), a greater proportion with CES-D scores ≥16, and a greater percentage who used antidepressant medications (P's < .01) than men. Although men had higher mean DBP levels than women (P < .05), greater proportions of women had hypertension  and a medical history of CVD (P's <.001). In addition, women met more clinical cut-offs for low HDL-C (P < .001), elevated hsCRP (P < .001), and high WHR (P < .01) than men. A greater proportion of men than women had high TG (P < .05) and alcohol consumption within the last week (P < .001), as well as lifetime smoking of ≥100 cigarettes and lifetime drug history of using cocaine, opiates, or marijuana ≥5 times (P's < .001).The mean age was 48 years old, and about 43% of participants had household incomes below 125% of the poverty level for their family size . Women hP's <.05) and lower levels of HDL-C (P < .01) in regressions, after adjustment for covariates. The associations of CES-D scores with WHR and HDL-C, but not SBP, were indicated in unadjusted regressions (P's <.05) among women. In contrast, men showed only a significant association between greater CES-D scores and higher levels of hsCRP (P < .05) in the adjusted regression model, as well as the unadjusted regression model. Depressive symptoms were differentially associated with CVD risk factors (continuous scores) according to sex . Among w Adjusted logistic regression models of CES-D scores on clinical cut-offs for CVD risk factors also revealed sex differences . Among wMetabolic syndrome in depressed versus nondepressed  participants varied by sex . Though  Among this community-based samples of young to middle-aged African Americans, higher levels of depressive symptoms in women were related to greater SBP and odds of hypertension, greater WHR and odds of abdominal obesity, lower HDL-C with greater odds of low HDL-C, and greater odds of metabolic syndrome. Depressive symptoms in men were associated with greater odds of hypertension and with higher levels of hsCRP. Despite only slightly higher mean scores on the CES-D in women, the associations between depressive symptoms and CVD risk factors differed notably by sex. Although very few prior studies have explicitly focused on African American samples, there is a relatively large literature available on sex differences in the association of depressive symptoms with cardiovascular risk factors. Comparison with prior literature is discussed below.Our findings that depressive symptoms were positively associated with SBP levels among women were consistent with findings from an all-female study of relatively healthy African American girls and women  that adjn = 159; ages 13 to 90) noted an association between CES-D scores ≥16 and hypertension [Results of the present study further indicate an association between higher CES-D scores and greater odds of hypertension in both African American men and women. Although no directly comparable studies of African American men were found, a smaller all-female study of relatively healthy African American girls and women  reported a positive association between CES-D scores and WHR levels after controlling for socioeconomic confounders [Depressive symptoms were associated with a greater WHR and higher odds of abdominal obesity in women, but not men. No directly comparable studies of African American women were located. However, a smaller study of African American adults  noted here is inconsistent with several reports of no association in either sex , 20, inc In contrast to continuous hsCRP, high levels of hsCRP (defined as hsCRP ≥3 mg/L) were not associated with CES-D in men, possibly due to statistical power. Prior studies with a racially diverse sample found a link between history of major depression and C-reactive protein levels ≥.22 mg/dL , 35, butThe more than doubling of odds for metabolic syndrome among women with clinically relevant levels of depressive symptoms in this study is notable, as metabolic syndrome is associated with a 2-fold increase in the risk of myocardial infarction, stroke, CVD incidence, and CVD mortality . A meta- It is clear that prior research on the associations between depressive symptoms and cardiovascular risk factors has yielded a highly mixed and methodologically dissimilar body of work. This relates to differential methods of sampling, operationalizing depression, risk factor outcomes, and variable adjustment for confounders. Of perhaps the greatest concern is the need for further research that accounts for critical medical confounders and medications, as well as medication adherence  to deter An additional consideration is that the geographic location of any particular study also may influence its findings. Most of the literature on sex differences in the association between depression and CVD risk factors is derived from samples outside of the USA , 21–33.  Lastly, stress-related autonomic nervous system, neuroendocrine, and immune pathways may be relevant and may vary by sex. For example, research on predominantly White samples suggests that autonomic nervous system activity is influenced more by the parasympathetic system among women, while the sympathetic system is more influential among men , 53. As This study contributes to the literature on depression and CVD risk factors by expanding the information available on sex differences in general, but particularly within African Americans. The study is strengthened by its examination of a spectrum of risk factors using both continuous measures and established clinical cut-offs. It is also strengthened by its adjustments for confounders that are often overlooked in similar studies  and by its utilization of the CES-D scale, which has been widely used in cardiovascular research and allows for comparisons across studies. Further, the use of continuous CES-D scores provided evaluation of the associations with CVD risk factors across the spectrum of depressive mood severity.The study is limited by its use of self-reported measures , dichotomized variables , and an alcohol measure that assessed how recently alcohol was consumed rather than quantity. It also has limitations in its generalizability to other research settings and other populations. Approximately 43% of this sample was impoverished . While this level of poverty was representative of the Baltimore City neighborhoods that were sampled, the results may have limited generalizability to African American populations in other locations that have fewer people living in poverty. Men had lower mean CES-D scores and a lower proportion with CES-D ≥16 than women. While it is possible that this may have influenced our results, we do not feel that the lower level of depressive symptoms among men interfered with our ability to detect associations in this group because the range of continuous CES-D scores in men was not truncated and the proportion of men with CES-D ≥16 was nearly 22%. Finally, its cross-sectional design cannot establish temporal associations between depression and CVD risk factors.Overall, our findings suggest that young to middle-aged African American women and men living in Baltimore, MD, show similar relations between depressive symptoms and hypertension. Although depressive symptoms were also related to greater hsCRP in AA men, it is particularly concerning that depressed mood in African American women was further linked to increased odds of abdominal obesity, low HDL-C, and metabolic syndrome. It is thus possible that depressed mood may, in part, be a contributing factor to why young-to-middle aged African American women lack the same degree of female advantage in cardiovascular health found among similarly aged women of other racial/ethnic groups compared to their male counterparts. There is a dire need for better efforts in screening, prevention, and intervention with cardiovascular risk factors among African Americans, particularly women. Further research is needed to assess the mechanisms that underlie the differential associations of depressive symptoms with cardiovascular risk profiles in African American men and women.


Crystallographic orientation of the ZnO nanorods and ZnO-ALD films was determined by X-ray diffraction analysis. Composition, morphologies, length, size, and diameter of the nanorods were studied using a scanning electron microscope and energy dispersed x-ray spectroscopy analyses. In this work, it is demonstrated that crystallinity of the ZnO-ALD films plays an important role in the vertical-aligned ZnO nanorod growth. The nanorod arrays synthesized in solution had a diameter, length, density, and orientation desirable for a potential application as photosensitive materials in the manufacture of semiconductor-polymer solar cells.A hydrothermal method to grow vertical-aligned ZnO nanorod arrays on ZnO films obtained by atomic layer deposition (ALD) is presented. The growth of ZnO nanorods is studied as function of the crystallographic orientation of the ZnO films deposited on silicon (100) substrates. Different thicknesses of ZnO films around 40 to 180 nm were obtained and characterized before carrying out the growth process by hydrothermal methods. A textured ZnO layer with preferential direction in the normal 61.46.Hk, Nanocrystals; 61.46.Km, Structure of nanowires and nanorods; 81.07.Gf, Nanowires; 81.15.Gh, Chemical vapor deposition  These versatile properties of ZnO provide an opportunity to recognize it as one of the most multifunctional materials; therefore it can be used for ultraviolet lasers, light-emitting diodes, photo-detectors, piezoelectric transducers and actuators, hydrogen storage, chemical or biosensors, surface acoustic-wave guides, solar cells, and photo catalysts, among others 2- which fits well with the (001) polyhedral surface, this spatial resonance increases the growth in this direction more that in another faces. (2) The {001} surface energy depends on the crystal thickness so that very thin ZnO crystals prefer a {001} orientation, which is then kinetically locked-in as growth proceeds. (3) The first few atomic layers of ZnO must adopt a low-energy configuration different from the bulk lattice and later convert to the (001) orientation by a minor structural transformation. Notwithstanding all mentioned above, it is deemed that microscopic analysis of seed formation must be developed to pinpoint the right mechanism responsible for nanorod alignment.The reason for the reported . Howeverc-axis-oriented seeds that favor the alignment, a long-term ALD deposit leads to create higher surface defects with polycrystalline seeds that promote disorder for ZnO nanorod growth. It is known that geometric parameters are tunable by changing the growth time and solution composition, with regards to the results of this work; this is also possible through changing seed density by controlling texture. Small thicknesses related with a short ALD deposit give seeded surfaces with small highly c-axis-oriented domains that promote small diameters with low density of nanorods while long-term ALD experiments disrupt the ordered growth. The best conditions occur for middle-term ALD deposits in which the c-axis orientation is preserved and size domain increases to get bigger diameters for nanorods. The arrays grown from aqueous solution feature a nanorod diameter, length, density, and orientation that make them highly suitable as the inorganic scaffold in efficient nanorod-polymer solar cells.A simple seeding method for producing vertical ZnO nanorod arrays on Si(100) substrates is presented. By forming layers of textured ZnO films by ALD on a substrate, a seeded surface can be used to fabricate high-density vertical nanorod arrays. From the results, it is observed that thickness influences the texture of ALD-ZnO layer and thus, the crystallographic nature of the seed layer that determines the ulterior nanostructure growth type. Whereas short-term ALD deposit leads to create a surface with mostly 3)2.1D: one-dimensional; AFM: atomic force microscopy; AH: average height; ALD: atomic layer deposition; DEZn: diethylzinc; DSSCs: dye-sensitized solar cells; EDS: energy dispersed x-ray spectroscopy; FE-SEM: field emission scanning electron microscope; HMT: hexamethylenetetramine; JCPDS: Joint Committee on Powder Diffraction Standards; PDF: powder diffraction file; SEM: scanning electron microscopy; XRD: X-ray diffraction; ZNT: Zn(NOThe authors declare that they have no competing interests.FP carried out the hydrothermal synthesis and drafted the manuscript. EM carried out the ALD-ZnO textured substrates, developed the XRD, AFM, and SEM studies and drafted the manuscript. MFM participated in discussion of results contributing with his experience on this topic and contributed with the writing of manuscript. EP contributed with fruitful discussions to the presented research. All authors read and approved the final manuscript.


Clinical data, especially long-term follow-up, is limited in CAPS due to its extreme rarity. We report here the design of a global observational registry for canakinumab (Ilaris®). The registry is monitored by an external steering committee with expertise in auto-inflammatory disease and registry design.The primary objective is to monitor overall safety of routine care with canakinumab in a large cohort (N≥400) of CAPS patients. Secondary objectives include exploring growth and development patterns in children and to measure the long-term impact of canakinumab on disease progression.CAPS patients receiving canakinumab as part of their routine care are included in this study for a minimum of 5-years follow-up. Data from routine clinic assessments is supplied at 6-monthly intervals via a web-based application. Selected safety events potentially associated with anti-IL-1 therapy such as serious infections, malignancies, hypersensitivity and disease activity/progression is analyzed. Signs and symptoms of systemic inflammation, neurologic and ophthalmologic status and the potential for canakinumab therapy to prevent amyloidosis and to ameliorate sensorineural deafness are assessed. Patterns of growth/development, pregnancies, outcomes of vaccination, dosing pattern and tolerability are ascertained. All patients are followed until the registry ends.Baseline data from the first 60 CAPS patients, including 15 pediatric patients (age <18 years), enrolled to date, are presented in table Baseline characteristics of the 60 patients enrolled to date demonstrate an expected disease background. Upon availability of a larger data-set, subanalyses will yield valuable insights into disease characteristics and modification properties of canakinumab.


Cardioplexol® (Swiss Cardio Technologies) is a hyperkalemic, low-dose, single-shot cardioplegic solution which offers immediate asystole of the heart, maintenance up to 90 minutes and immediate reversal of asystole after release of cross clamp. Intermittent crossclamping with Lidoflazine is the current operative technique used in our center. Main question was whether Cardioplexol is an efficient, safe, easy-to-use and worthy alternative to Lidoflazine in elective isolated CABG in low-risk patients. Primary outcomes are heart enzymes (cTnI and CK-MB) and secondary outcomes are operation times, length of stay, major complications and in-hospital mortality.From December 2011 to May 2013 40 patients, with LVEF ≥50%, EuroSCORE II <3,5% and no severe systemic disease, underwent elective CABG and were consecutively randomized to intermittent crossclamping  or Cardioplexol . All were operated on by the same surgeon.There was no significant difference in age , EuroSCORE II  or number of distal anastomoses . We found no significant difference for maximum cTnI  or maximum CK-MB . ECC time  and cross-clamp time  were not significantly different. Neither length of hospital stay  nor postoperative complications  showed significant difference. There was no in-hospital mortality.In this elective CABG population with low risk, Cardioplexol offered good myocardial protection, with comparable primary and secondary outcomes. Further studies are needed to expand its use.


Overcrowding in U.S. emergency departments (ED) is a critical issue. In a privatized health care system, patients with limited access to insurance benefits  often utilize the ED as crucial point of access to care. Non-acute patients seeking primary care in ED facilities can congest operations and contribute to overcrowding. In Hawaii’s second busiest ED , a non-traditional method of emergency triage – team triage – has been implemented to improve patient throughput and satisfaction, and mitigate effects of overcrowding. This study defines trends and compares two prominent and nationally recognized EDs  in the state of Hawaii - employing team and traditional triage respectively, to examine changes in patient population, demographics, acuteness, and departmental throughput measures.Retrospective data review from 180,000+ patient records  was obtained from July 2007 – June 2010 through the electronic medical records system, EPIC. Data included patient demographics, mode of arrival, length of stay (LOS), door-to-doctor time, insurance type, and patient satisfaction. Statistical analysis was completed with JMP and SPSS statistical software.Patient volume increased over the 36 month time period at both hospitals as did patient satisfaction, particularly after the implementation of team triage at Hospital 1. The door-to-doctor time decreased for outpatients at both hospitals as well, but the overall LOS for outpatients remained largely the same. The percentage of governmentally insured (as opposed to privately insured) patients increased, but surrogate measures of acuteness - ambulance arrivals and admission rates – declined amongst this population.Trends in satisfaction and door-to-doctor time are not exclusive to a team triage environment. Team triage potentially reduces door-to-doctor time, but has minimal impact on overall LOS. There exists a disparity in patient population and relative acuity that can contribute to overcrowding and patient throughput. Ultimately inpatient resources – not method of triage or even ED throughput – may be the biggest determining factor in improving overcrowding in EDs outside of health policy changes and reform.