Readiness Of Medical Providers In The Military Health System: Overview Of Operational And Policy Considerations.

US military forces have diverse missions, including combat, response to natural disasters, humanitarian assistance, training, and diplomacy. The military's medical forces, composed of clinical providers from the Army, Navy, and Air Force, support these operations-often on a moment's notice. The Military Health System (MHS) must ensure that medical providers are always trained and equipped to deliver care when deployed on missions in often austere environments.

A new bioinformatics tool to help assess the significance of BRCA1 variants.

Background: Germline pathogenic variants in the breast cancer type 1 susceptibility gene BRCA1 are associated with a 60% lifetime risk for breast and ovarian cancer. This overall risk estimate is for all BRCA1 variants; obviously, not all variants confer the same risk of developing a disease. In cancer patients, loss of BRCA1 function in tumor tissue has been associated with an increased sensitivity to platinum agents and to poly-(ADP-ribose) polymerase (PARP) inhibitors.

Divergent artificial selection for female reproductive investment has a sexually concordant effect on male reproductive success.

Depending on the genetic architecture of male and female fitness, sex-specific selection can have negative, positive, or neutral consequences for the opposite sex. Theory predicts that conflict between male and female function may drive the breakdown of intrasexual genetic correlations, allowing sexual dimorphism in sexually antagonistic traits. Reproductive traits are the epitome of this, showing highly differentiated proximate functions between the sexes.

Increased prenatal maternal investment reduces inbreeding depression in offspring.

Inbreeding depression refers to the reduction of fitness that results from matings between relatives. Evidence for reduced fitness in inbred individuals is widespread, but the strength of inbreeding depression varies widely both within and among taxa. Environmental conditions can mediate this variation in the strength of inbreeding depression, with environmental stress exacerbating the negative consequences of inbreeding.

Disentangling Genetic and Prenatal Maternal Effects on Offspring Size and Survival.

Organizational processes during prenatal development can have long-term effects on an individual's phenotype. Because these early developmental stages are sensitive to environmental influences, mothers are in a unique position to alter their offspring's phenotype by differentially allocating resources to their developing young. However, such prenatal maternal effects are difficult to disentangle from other forms of parental care, additive genetic effects, and/or other forms of maternal inheritance, hampering our understanding of their evolutionary consequences.

Artificial selection reveals the energetic expense of producing larger eggs.

Background: The amount of resources provided by the mother before birth has important and long-lasting effects on offspring fitness. Despite this, there is a large amount of variation in maternal investment seen in natural populations. Life-history theory predicts that this variation is maintained through a trade-off between the benefits of high maternal investment for the offspring and the costs of high investment for the mother.

Efficiency of the Switching Process in Organic Electrochemical Transistors.

Unlabelled: Entirely screen printed organic electrochemical transistors (OECTs) based on poly(3,4-ethylenedioxithiophene) poly(styrenesulfonate) (

Pedot: PSS) and a polymer electrolyte are investigated in view of a correlation between the electrical charge consumed during switching and the volume of

Pedot: PSS in the transistor channel. An understanding of the relation between charge consumption and the amount of electrochemically active PEDOT is essential for the design of high performance transistors and for providing a deeper insight into the fundamentals of the electrochemical switching process in OECTs. It turned out that a precise control of the width of the

Pedot: PSS source-drain line is imperative for maximizing both the on-current and the on/off current ratio of lateral OECTs.

In search of genetic constraints limiting the evolution of egg size: direct and correlated responses to artificial selection on a prenatal maternal effector.

Maternal effects are an important force in nature, but the evolutionary dynamics of the traits that cause them are not well understood. Egg size is known to be a key mediator of prenatal maternal effects with an established genetic basis. In contrast to theoretical expectations for fitness-related traits, there is a large amount of additive genetic variation in egg size observed in natural populations.

Risk Analysis of Prostate Cancer in PRACTICAL, a Multinational Consortium, Using 25 Known Prostate Cancer Susceptibility Loci.

Background: Genome-wide association studies have identified multiple genetic variants associated with prostate cancer risk which explain a substantial proportion of familial relative risk. These variants can be used to stratify individuals by their risk of prostate cancer.

Methods: We genotyped 25 prostate cancer susceptibility loci in 40,414 individuals and derived a polygenic risk score (PRS).

Effects of trophy hunting leftovers on the ranging behaviour of large carnivores: a case study on spotted hyenas.

Human-related food resources such as garbage dumps and feeding sites have been shown to significantly influence space use, breeding success and population dynamics in a variety of animal species. In contrast, relatively little is known on the effects of unpredictable sources of food, such as carcasses discarded by hunters, on carnivore species. We evaluated the effect of elephant carcasses, mainly deriving from trophy hunting, on the ranging and feeding behavior of spotted hyenas (Crocuta crocuta) in the Okavango Delta, Botswana.

High-resolution breakpoint analysis provides evidence for the sequence-directed nature of genome rearrangements in hereditary disorders.

Although most of the pertinent data on the sequence-directed processes leading to genome rearrangements (GRs) have come from studies on somatic tissues, little is known about GRs in the germ line of patients with hereditary disorders. This study aims at identifying DNA motifs and higher order structures of genome architecture, which can result in losses and gains of genetic material in the germ line. We first identified candidate motifs by studying 112 pathogenic germ-line GRs in hereditary colorectal cancer patients, and subsequently created an algorithm, termed recombination type ratio, which correctly predicts the propensity of rearrangements with respect to homologous versus nonhomologous recombination events.

[Lynch syndrome: when pathologist and clinician have the opportunity to reduce the risk of developing cancer].

Lynch syndrome is an autosomal dominant disease associated with an important risk of cancer, mainly endometrial and colorectal-cancer. This risk can be efficiently lessen by an appropriate screening as far as the mutations carriers are identified. As current clinicopathological recommendations lack sensitivity, a systematic pre-screening of every patient with a colorectal or endometrial cancer can be proposed.

Recurrence and variability of germline EPCAM deletions in Lynch syndrome.

Recently, we identified 3' end deletions in the EPCAM gene as a novel cause of Lynch syndrome. These truncating EPCAM deletions cause allele-specific epigenetic silencing of the neighboring DNA mismatch repair gene MSH2 in tissues expressing EPCAM. Here we screened a cohort of unexplained Lynch-like families for the presence of EPCAM deletions.

Risk of colorectal and endometrial cancers in EPCAM deletion-positive Lynch syndrome: a cohort study.

Background: Lynch syndrome is caused by germline mutations in MSH2, MLH1, MSH6, and PMS2 mismatch-repair genes and leads to a high risk of colorectal and endometrial cancer. We previously showed that constitutional 3' end deletions of EPCAM can cause Lynch syndrome through epigenetic silencing of MSH2 in EPCAM-expressing tissues, resulting in tissue-specific MSH2 deficiency. We aim to establish the risk of cancer associated with such EPCAM deletions.

Selection of patients with germline MLH1 mutated Lynch syndrome by determination of MLH1 methylation and BRAF mutation.

Lynch syndrome is one of the most common hereditary colorectal cancer (CRC) syndrome and is caused by germline mutations of MLH1, MSH2 and more rarely MSH6, PMS2, MLH3 genes. Whereas the absence of MSH2 protein is predictive of Lynch syndrome, it is not the case for the absence of MLH1 protein. The purpose of this study was to develop a sensitive and cost effective algorithm to select Lynch syndrome cases among patients with MLH1 immunohistochemical silencing.

Identification of seven new prostate cancer susceptibility loci through a genome-wide association study.

Prostate cancer (PrCa) is the most frequently diagnosed cancer in males in developed countries. To identify common PrCa susceptibility alleles, we previously conducted a genome-wide association study in which 541,129 SNPs were genotyped in 1,854 PrCa cases with clinically detected disease and in 1,894 controls. We have now extended the study to evaluate promising associations in a second stage in which we genotyped 43,671 SNPs in 3,650 PrCa cases and 3,940 controls and in a third stage involving an additional 16,229 cases and 14,821 controls from 21 studies.

Age-Dependent Cancer Risk Is Not Different in between MSH2 and MLH1 Mutation Carriers.

Lynch syndrome is mostly characterized by early-onset colorectal and endometrial adenocarcinomas. Over 90% of the causal mutations occur in two mismatch repair genes, MSH2 and MLH1. The aim of this study was to evaluate the age-dependent cancer risk in MSH2 or MLH1 mutation carriers from data of DNA diagnostic laboratories.

Rapidly evolving Rab GTPase paralogs and reproductive isolation in Drosophila.

Alterations at the X-linked Hmr gene of Drosophila melanogaster can fully restore viability and partially restore fertility in hybrid flies from crosses between D. melanogaster and any of its three most closely related species. Although more than one gene is expected to be involved in these barriers to reproduction, a single DNA-binding protein was recently identified as HMR.

A case of Muir-Torre syndrome associated with mucinous hepatic cholangiocarcinoma and a novel germline mutation of the MSH2 gene.

Muir-Torre syndrome (MTS) is a rare cancer-predisposing syndrome that is autosomal dominantly inherited and characterized by the development of sebaceous skin lesions (adenomas, epitheliomas, basaliomas and carcinomas). These lesions are typically associated with tumors that belong to the spectrum of hereditary nonpolyposis colorectal cancer (HNPCC) (i.e.

[Colorectal cancer: a risk-adapted screening and the role of the physician in the prevention of this cancer].

The benefit of colorectal cancer screening in the average-risk population, as well as in the presence of high risk genetic predispositions, has been validated by a significant reduction of the mortality associated with the disease. Several screening options are recognized and compliance with these measures remains a public health problem. The physician plays a key role in the promotion of the colorectal cancer screening.

Double frameshift mutations in APC and MSH2 in the same individual.

Heterozygous germline DNA mismatch repair gene mutations are typically associated with HNPCC. Here we report the case of a proband whose father was known for familial adenomatous polyposis. The number of polyps (less than ten) was not typical of polyposis; therefore, the diagnosis of HNPCC was entertained.