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Homology-directed repair of DNA double-strand breaks (DSBs) can be a highly faithful pathway. Non-crossover repair dominates in mitotically growing cells, likely through a preference for synthesis-dependent strand annealing (SDSA). While genetic studies highlight a key role for the RecQ helicase BLM/Rqh1 (in human and S. pombe cells, respectively) in promoting noncrossover repair, how homology-directed repair mechanism choice is orchestrated in time and space is not well understood. Here, we develop a microscopy-based assay in living fission yeast to determine the dynamics and kinetics of an engineered, site-specific interhomologue repair event. We observe highly efficient homology search and homology-directed repair in this system. Surprisingly, we find that the initial distance between the DSB and the donor sequence does not correlate with the duration of repair. Instead, we observe that repair is likely to involve multiple site-specific and Rad51-dependent co-localization events between the DSB and donor sequence, suggesting that efficient interhomologue repair in fission yeast often involves multiple strand invasion events. By contrast, we find that loss of Rqh1 leads to successful repair through a single strand invasion event, suggesting that multiple strand invasion cycles reflect ongoing SDSA. However, failure to repair is also more likely in rqh1Δ cells, which could reflect increased strand invasion at non-homologous sites. This work has implications for the molecular etiology of Bloom syndrome, caused by mutations in BLM and characterized by aberrant sister chromatid crossovers and inefficient repair.

Background Deployment-related experiences might be risk factors for soldier suicides, in which case identification of vulnerable soldiers before deployment could inform preventive efforts. We investigated this possibility by using pre-deployment survey and administrative data in a sample of US Army soldiers to develop a risk model for suicide attempt (SA) during and shortly after deployment. Methods Data came from the Army Study to Assess Risk and Resilience in Servicemembers Pre-Post Deployment Survey (PPDS). Soldiers completed a baseline survey shortly before deploying to Afghanistan in 2011–2012. Survey measures were used to predict SAs, defined using administrative and subsequent survey data, through 30 months after deployment. Models were built using penalized regression and ensemble machine learning methods. Results Significant pre-deployment risk factors were history of traumatic brain injury, 9 + mental health treatment visits in the 12 months before deployment, young age, female, previously married, and low relationship quality. Cross-validated AUC of the best penalized and ensemble models were .75–.77. 21.3–40.4% of SAs occurred among the 5–10% of soldiers with highest predicted risk and positive predictive value (PPV) among these high-risk soldiers was 4.4–5.7%. Conclusions SA can be predicted significantly from pre-deployment data, but intervention planning needs to take PPV into consideration.

The choice of the standard population is important when calculating adjusted rates for a military population: results can influence policies and funding allocations for programs and initiatives for suicide prevention. We describe the methodological considerations and decision-making process used in choosing a standard population for adjusting rates to compare suicide among US Army soldiers and the general US population. We examined 5 different standard populations, using the direct method to adjust annual suicide rates for the Army and the US population, 2004 to 2015, for age and for age and sex. The pattern of the Army and US population age- and sex-adjusted rates remained consistent with crude rates when adjusted to any of the Army standard population distributions. Using an Army distribution as the standard population produces suicide rates consistent with routine messaging about suicide trends among Army soldiers.

Physical therapists' perceptions of sexual boundaries in clinic settings in the United States have not been studied. Given the magnitude of potential consequences of sexual boundary violations, examination of this topic is imperative.The purpose of this study was to describe the perceptions of sexual boundaries among licensed physical therapists in the United States.Licensed physical therapists from Arkansas, Kansas, Maine, Ohio, and Oregon were contacted by email and asked to complete a sexual boundaries questionnaire via Survey Monkey™; 967 surveys (7.3%) were returned.While most physical therapists practice within the profession's Code of Ethics, there are practitioners who date current and former patients, and condone patients' sexual banter in the clinic. Almost half (42%) of the participants acknowledged feeling sexually attracted to a patient. While gender differences were seen throughout the analyses, generally, the demographic and professional variables did not account for meaningful variance. Results were similar to previous research on physiotherapists in other countries.Sexuality is part of the physical therapy practice environment and physical therapists' understanding of sexual boundaries is ambiguous. These data can inform professional conversation on sexual boundaries in physical therapy practice leading to greater understanding and decreased potential for violations.

OBJECTIVE To investigate whether trauma exposure moderates the genetic correlation between substance use disorders and psychiatric disorders, we tested whether trauma exposure modifies the association of genetic risks for mental disorders with alcohol misuse and nicotine dependence (ND) symptoms. METHODS High-resolution polygenic risk scores (PRSs) were calculated for 10 732 US Army soldiers (8346 trauma-exposed and 2386 trauma-unexposed) based on genome-wide association studies of bipolar disorder (BD), major depressive disorder, and schizophrenia. RESULTS The main finding was a significant BD PRS-by-trauma interaction with respect to alcohol misuse (P = 6.07 × 10-3 ). We observed a positive correlation between BD PRS and alcohol misuse in trauma-exposed soldiers (r = 0.029, P = 7.5 × 10-3 ) and a negative correlation in trauma-unexposed soldiers (r = -0.071, P = 5.61 × 10-4 ). Consistent (nominally significant) result with concordant effect, directions were observed in the schizophrenia PRS-by-trauma interaction analysis. The variants included in the BD PRS-by-trauma interaction showed significant enrichments for gene ontologies related to high voltage-gated calcium channel activity (GO:0008331, P = 1.51 × 10-5 ; GO:1990454, P = 4.49 × 10-6 ; GO:0030315, P = 2.07 × 10-6 ) and for Beta1/Beta2 adrenergic receptor signaling pathways (P = 2.61 × 10-4 ). CONCLUSIONS These results indicate that the genetic overlap between alcohol misuse and BD is significantly moderated by trauma exposure. This provides molecular insight into the complex mechanisms that link substance abuse, psychiatric disorders, and trauma exposure.

This paper provides a synthesis of information from extant research and policy documentation on information technology (IT) workforce issues in the US and abroad. In particular, it addresses some of the issues that concerned the USA's 21st Century Workforce Commission, which was established to look at the IT labour market. It defines the IT market fairly broadly and is concerned with the overall IT workforce. The paper covers both supply and demand issues and looks to address a variety of questions concerning the longer-term nature of IT employment and any potential labour market imperfections that may arise through inappropriate educational strategies. It looks at the skills needed to obtain IT jobs, ways to increase the supply of IT workers, and describes and assesses a number of foreign programmes for training individuals for IT employment.

Tolerance has been defined as stable graft function off IMS. We reviewed the data of 369 pediatric liver transplant patients to examine demographic differences that may have a PV of pediatric LT tolerance. Of the 369 patients, 280 patients were stable with detectable blood levels of IMS agents and with good graft function without biopsy proven REJ1 yr posttransplantation, 18 patients were noted to be TOL off IMS, 27 patients were taking MIS with drug levels below detectable range by standard laboratory parameters, and 44 patients developed one or more episodes of biopsy proven acute or chronic REJ1 yr post-transplantation. Variables, including percentage of biliary atresia, type of transplanted organ, history of EBV infection, patient and donor gender, and ABO blood type mismatch between recipient and donor did not have PV of tolerance. Average age in years was 1.37 ± 1.53 (0.3-4.9) for TOL, 1.14 ± 0.89 (0.4-3.1) for MIS and 3.35 ± 4.45 (0.3-16) for REJ. Age difference of TOL/MIS vs. REJ was significant (p =0.002) and TOL vs. REJ was significant (0.01). Age at the time of transplantation is an important predictor in the development of pediatric LT tolerance.

Economic multipliers are widely used in regional impact and policy analysis. A substantial literature has developed, defining multipliers and offering guidelines on estimation. This has also been tied to developments in regional growth theory, economic impact analysis, and input output analysis. The importance of regional multiplier analysis is likely to grow as infrastructure programmes are seen as important inputs into economic productivity growth initiatives and as fiscal transfers take on a more prominent role in economic integrations (e.g., the European Union, NAFTA, and the African Union). This paper is concerned with the problems of defining appropriate multiplicands, the initial injections that drive multipliers, at the regional level. Setting aside the literature on the export growth model, this aspect of impact analysis has been relatively neglected. The study presented here, of environmental expenditures in the Upper Mississippi River Basin, looks at some of the problems of using publicly available data to develop and derive a meaningful multiplicand.

This is a retrospective study of upper gastrointestinal testinal hemorrhage in 68 children and adolescents who were less than 19 years old. In descending order of frequency, the five most common causes were duodenal ulcers, gastric ulcers, esophagitis, gastritis, and esophageal varices. There was male predominance in all diagnoses except gastric ulcers and gastritis. Signs and symptoms correlated poorly with the source of bleeding. Endoscopy was the most reliable method of identifying the bleeding site. Mortality correlated with the following: (1) initial hematocrit or hemoglobin level of 85 ml/kg of blood without surgical intervention, (3) failure to identify the source of bleeding, (4) presence of a coagulation disorder, and (5) coexistence of another life-threatening disease.

A number of Robert Creeley's poems, certainly most of the best, are in form addresses to another being. They differ from the absolute subjective outcry addressed to no-one in particular or the universe in general (lyric) and from statement attributed as if objective to various persons addressing one another (drama). In the category to which these poems belong the writer speaks in his own person to someone else. Among the verse-forms used in English the sonnet became for a long time practically identified with it. It is of the nature of the address that the being spoken to should remain mute. The poems are obliged to perform their act or exercise without benefit of participation and without the aid of answer or cue: for any such aid they can only look to the practice of self-examination. In this onesidedness they partake of the nature of an act of homage or worship, an oblation to a divinity, a gift to a friend, a love-token. There may be response supposed, but none which really influences the act. Nevertheless