Novel biomarkers and endoscopic techniques for diagnosing pancreaticobiliary malignancy

The UK incidence of pancreatic ductal adenocarcinoma is 9 per 100,000 population, and biliary tract cancer occurs at a rate of 1-2 per 100,000. The incidence of both cancers is increasing annually and these tumours continue to be diagnosed late and at an advanced stage, limiting options for curative treatment. Population-based screening programmes do not exist for these cancers, and diagnosis currently is dependent on symptom recognition, but often symptoms are not present until the disease is advanced. Recently, a number of promising blood and urine biomarkers have been described for pancreaticobiliary malignancy and are summarised in this review. Novel endoscopic techniques such as single-operator cholangioscopy and confocal endomicroscopy have been used in some centres to enhance standard endoscopic diagnostic techniques and are also evaluated in this review

Searching for Exoplanets Using a Microresonator Astrocomb

Detection of weak radial velocity shifts of host stars induced by orbiting planets is an important technique for discovering and characterizing planets beyond our solar system. Optical frequency combs enable calibration of stellar radial velocity shifts at levels required for detection of Earth analogs. A new chip-based device, the Kerr soliton microcomb, has properties ideal for ubiquitous application outside the lab and even in future space-borne instruments. Moreover, microcomb spectra are ideally suited for astronomical spectrograph calibration and eliminate filtering steps required by conventional mode-locked-laser frequency combs. Here, for the calibration of astronomical spectrographs, we demonstrate an atomic/molecular line-referenced, near-infrared soliton microcomb. Efforts to search for the known exoplanet HD 187123b were conducted at the Keck-II telescope as a first in-the-field demonstration of microcombs

Regulatory de novo mutations underlying intellectual disability

The genetic aetiology of a major fraction of patients with intellectual disability (ID) remains unknown. De novo mutations (DNMs) in protein-coding genes explain up to 40% of cases, but the potential role of regulatory DNMs is still poorly understood. We sequenced 63 whole genomes from 21 ID probands and their unaffected parents. In addition, we analysed 30 previously sequenced genomes from exome-negative ID probands. We found that regulatory DNMs were selectively enriched in fetal brain-specific enhancers as compared with adult brain enhancers. DNM-containing enhancers were associated with genes that show preferential expression in the prefrontal cortex. Furthermore, we identified recurrently mutated enhancer clusters that regulate genes involved in nervous system development (CSMD1, OLFM1, and POU3F3). Most of the DNMs from ID probands showed allele-specific enhancer activity when tested using luciferase assay. Using CRISPR-mediated mutation and editing of epigenomic marks, we show that DNMs at regulatory elements affect the expression of putative target genes. Our results, therefore, provide new evidence to indicate that DNMs in fetal brain-specific enhancers play an essential role in the aetiology of ID

Polyfunctional T cell responses in children in early stages of chronic Trypanosoma cruzi infection contrast with monofunctional responses of long-term infected adults

Background: Adults with chronic Trypanosoma cruzi exhibit a poorly functional T cell compartment, characterized by monofunctional (IFN-γ-only secreting) parasite-specific T cells and increased levels of terminally differentiated T cells. It is possible that persistent infection and/or sustained exposure to parasites antigens may lead to a progressive loss of function of the immune T cells. Methodology/Principal Findings: To test this hypothesis, the quality and magnitude of T. cruzi-specific T cell responses were evaluated in T. cruzi-infected children and compared with long-term T. cruzi-infected adults with no evidence of heart failure. The phenotype of CD4+ T cells was also assessed in T. cruzi-infected children and uninfected controls. Simultaneous secretion of IFN-γ and IL-2 measured by ELISPOT assays in response to T. cruzi antigens was prevalent among T. cruzi-infected children. Flow cytometric analysis of co-expression profiles of CD4+ T cells with the ability to produce IFN-γ, TNF-α, or to express the co-stimulatory molecule CD154 in response to T. cruzi showed polyfunctional T cell responses in most T. cruzi-infected children. Monofunctional T cell responses and an absence of CD4+TNF-α+-secreting T cells were observed in T. cruzi-infected adults. A relatively high degree of activation and differentiation of CD4+ T cells was evident in T. cruzi-infected children. Conclusions/Significance: Our observations are compatible with our initial hypothesis that persistent T. cruzi infection promotes eventual exhaustion of immune system, which might contribute to disease progression in long-term infected subjects.Fil: Albareda, María Cecilia. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: de Rissio, Ana María. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; ArgentinaFil: Tomas, Gonzalo. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; ArgentinaFil: Serjan, Alicia. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; ArgentinaFil: Alvarez, María Gabriela. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Viotti, Rodolfo Jorge. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Fichera, Laura Edith. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Esteva, Mónica Inés. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; ArgentinaFil: Potente, Daniel Fernando. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Armenti, Alejandro. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Tarleton, Rick L.. University of Georgia; Estados UnidosFil: Laucella, Susana Adriana. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Preventing Post-ERCP Pancreatitis: The Role of Prophylactic Pancreatic Duct Stenting in the Rectal NSAID Era

Background: Rectal non-steroidal anti-inflammatory drug at endoscopic retrograde cholangiopancreatography is now the standard of care to reduce the risk of post-ERCP pancreatitis. Pancreatic duct stenting also reduces the risk of post- ERCP pancreatitis in high-risk patients, but failed pancreatic duct stenting carries an increased PEP rate (up to 35%). Study Aim: To assess the impact on post-ERCP pancreatitis of successful and unsuccessful pancreatic duct stent placement in the setting of universal rectal non-steroidal anti-inflammatory drug use. Methods: Between 2013-2015, all patients undergoing endoscopic retrograde cholangiopancreatographys in our tertiary referral centre (where rectal non-steroidal anti-inflammatory drugs are used routinely) were included. The electronic patient's records were reviewed and the following parameters were analysed: indication for pancreatic duct stenting; deployment success; and adverse events. Results: A total of 1633 endoscopic retrograde cholangiopancreatographys were performed, and pancreatic duct stenting was attempted in 324 cases (20%), with successful placement in 307 patients (95%). Contra-indications to non-steroidal anti-inflammatory drugs were found in 106 (6.5%) patients. Prophylactic stenting failed in 12 of 213 patients; of whom one patient developed post-ERCP pancreatitis (8%). Eighteen (9%) patients with prophylactic pancreatic duct stents developed post-ERCP pancreatitis compared to 1.4% without prophylactic stents (RR 8.4, p=0.04). Conclusion: A lack of difference in post-ERCP pancreatitis in those who underwent successful, and unsuccessful, pancreatic duct stent placement may reflect the protective effect of non-steroidal anti-inflammatory drugs. This data adds to evidence suggesting that pancreatic duct stenting may be less important, even in high-risk patients, with the widespread use of non-steroidal anti-inflammatory drugs

Different atmospheric moisture divergence responses to extreme and moderate El Niños

On seasonal and inter-annual time scales, vertically integrated moisture divergence provides a useful measure of the tropical atmospheric hydrological cycle. It reflects the combined dynamical and thermodynamical effects, and is not subject to the limitations that afflict observations of evaporation minus precipitation. An empirical orthogonal function (EOF) analysis of the tropical Pacific moisture divergence fields calculated from the ERA-Interim reanalysis reveals the dominant effects of the El Niño-Southern Oscillation (ENSO) on inter-annual time scales. Two EOFs are necessary to capture the ENSO signature, and regression relationships between their Principal Components and indices of equatorial Pacific sea surface temperature (SST) demonstrate that the transition from strong La Niña through to extreme El Niño events is not a linear one. The largest deviation from linearity is for the strongest El Niños, and we interpret that this arises at least partly because the EOF analysis cannot easily separate different patterns of responses that are not orthogonal to each other. To overcome the orthogonality constraints, a self-organizing map (SOM) analysis of the same moisture divergence fields was performed. The SOM analysis captures the range of responses to ENSO, including the distinction between the moderate and strong El Niños identified by the EOF analysis. The work demonstrates the potential for the application of SOM to large scale climatic analysis, by virtue of its easier interpretation, relaxation of orthogonality constraints and its versatility for serving as an alternative classification method. Both the EOF and SOM analyses suggest a classification of “moderate” and “extreme” El Niños by their differences in the magnitudes of the hydrological cycle responses, spatial patterns and evolutionary paths. Classification from the moisture divergence point of view shows consistency with results based on other physical variables such as SST

Conceptualizing pathways linking women's empowerment and prematurity in developing countries.

BackgroundGlobally, prematurity is the leading cause of death in children under the age of 5. Many efforts have focused on clinical approaches to improve the survival of premature babies. There is a need, however, to explore psychosocial, sociocultural, economic, and other factors as potential mechanisms to reduce the burden of prematurity. Women's empowerment may be a catalyst for moving the needle in this direction. The goal of this paper is to examine links between women's empowerment and prematurity in developing settings. We propose a conceptual model that shows pathways by which women's empowerment can affect prematurity and review and summarize the literature supporting the relationships we posit. We also suggest future directions for research on women's empowerment and prematurity.MethodsThe key words we used for empowerment in the search were "empowerment," "women's status," "autonomy," and "decision-making," and for prematurity we used "preterm," "premature," and "prematurity." We did not use date, language, and regional restrictions. The search was done in PubMed, Population Information Online (POPLINE), and Web of Science. We selected intervening factors-factors that could potentially mediate the relationship between empowerment and prematurity-based on reviews of the risk factors and interventions to address prematurity and the determinants of those factors.ResultsThere is limited evidence supporting a direct link between women's empowerment and prematurity. However, there is evidence linking several dimensions of empowerment to factors known to be associated with prematurity and outcomes for premature babies. Our review of the literature shows that women's empowerment may reduce prematurity by (1) preventing early marriage and promoting family planning, which will delay age at first pregnancy and increase interpregnancy intervals; (2) improving women's nutritional status; (3) reducing domestic violence and other stressors to improve psychological health; and (4) improving access to and receipt of recommended health services during pregnancy and delivery to help prevent prematurity and improve survival of premature babies.ConclusionsWomen's empowerment is an important distal factor that affects prematurity through several intervening factors. Improving women's empowerment will help prevent prematurity and improve survival of preterm babies. Research to empirically show the links between women's empowerment and prematurity is however needed

Verbal autopsy completion rate and factors associated with undetermined cause of death in a rural resource-poor setting of Tanzania

UNLABELLED\ud \ud ABSTRACT:\ud \ud BACKGROUND\ud \ud Verbal autopsy (VA) is a widely used tool to assign probable cause of death in areas with inadequate vital registration systems. Its uses in priority setting and health planning are well documented in sub-Saharan Africa (SSA) and Asia. However, there is a lack of data related to VA processing and completion rates in assigning causes of death in a community. There is also a lack of data on factors associated with undetermined causes of death documented in SSA. There is a need for such information for understanding the gaps in VA processing and better estimating disease burden.\ud \ud OBJECTIVE\ud \ud The study's intent was to determine the completion rate of VA and factors associated with assigning undetermined causes of death in rural Tanzania.\ud \ud METHODS\ud \ud A database of deaths reported from the Ifakara Health and Demographic Surveillance System from 2002 to 2007 was used. Completion rates were determined at the following stages of processing: 1) death identified; 2) VA interviews conducted; 3) VA forms submitted to physicians; 4) coding and assigning of cause of death. Logistic regression was used to determine factors associated with deaths coded as "undetermined."\ud \ud RESULTS\ud \ud The completion rate of VA after identification of death and the VA interview ranged from 83% in 2002 and 89% in 2007. Ninety-four percent of deaths submitted to physicians were assigned a specific cause, with 31% of the causes coded as undetermined. Neonates and child deaths that occurred outside health facilities were associated with a high rate of undetermined classification (33%, odds ratio [OR] = 1.33, 95% confidence interval [CI] (1.05, 1.67), p = 0.016). Respondents reporting high education levels were less likely to be associated with deaths that were classified as undetermined (24%, OR = 0.76, 95% CI (0.60, -0.96), p = 0.023). Being a child of the deceased compared to a partner (husband or wife) was more likely to be associated with undetermined cause of death classification (OR = 1.35, 95% CI (1.04, 1.75), p = 0.023).\ud \ud CONCLUSION\ud \ud Every year, there is a high completion rate of VA in the initial stages of processing; however, a number of VAs are lost during the processing. Most of the losses occur at the final step, physicians' determination of cause of death. The type of respondent and place of death had a significant effect on final determination of the plausible cause of death. The finding provides some insight into the factors affecting full coverage of verbal autopsy diagnosis and the limitations of causes of death based on VA in SSA. Although physician review is the most commonly used method in ascertaining probable cause of death, we suggest further work needs to be done to address the challenges faced by physicians in interpreting VA forms. There is need for an alternative to or improvement of the methods of physician review

Disparities and risks of sexually transmissible infections among men who have sex with men in China: a meta-analysis and data synthesis.

BACKGROUND: Sexually transmitted infections (STIs), including Hepatitis B and C virus, are emerging public health risks in China, especially among men who have sex with men (MSM). This study aims to assess the magnitude and risks of STIs among Chinese MSM. METHODS: Chinese and English peer-reviewed articles were searched in five electronic databases from January 2000 to February 2013. Pooled prevalence estimates for each STI infection were calculated using meta-analysis. Infection risks of STIs in MSM, HIV-positive MSM and male sex workers (MSW) were obtained. This review followed the PRISMA guidelines and was registered in PROSPERO. RESULTS: Eighty-eight articles (11 in English and 77 in Chinese) investigating 35,203 MSM in 28 provinces were included in this review. The prevalence levels of STIs among MSM were 6.3% (95% CI: 3.5-11.0%) for chlamydia, 1.5% (0.7-2.9%) for genital wart, 1.9% (1.3-2.7%) for gonorrhoea, 8.9% (7.8-10.2%) for hepatitis B (HBV), 1.2% (1.0-1.6%) for hepatitis C (HCV), 66.3% (57.4-74.1%) for human papillomavirus (HPV), 10.6% (6.2-17.6%) for herpes simplex virus (HSV-2) and 4.3% (3.2-5.8%) for Ureaplasma urealyticum. HIV-positive MSM have consistently higher odds of all these infections than the broader MSM population. As a subgroup of MSM, MSW were 2.5 (1.4-4.7), 5.7 (2.7-12.3), and 2.2 (1.4-3.7) times more likely to be infected with chlamydia, gonorrhoea and HCV than the broader MSM population, respectively. CONCLUSION: Prevalence levels of STIs among MSW were significantly higher than the broader MSM population. Co-infection of HIV and STIs were prevalent among Chinese MSM. Integration of HIV and STIs healthcare and surveillance systems is essential in providing effective HIV/STIs preventive measures and treatments. TRIAL REGISTRATION: PROSPERO NO: CRD42013003721