A to Z of the Muon anomalous magnetic moment in the MSSM with Pati-Salam at the GUT scale

We analyse the low energy predictions of the minimal supersymmetric standard model (MSSM) arising from a GUT scale Pati-Salam gauge group further constrained by an A4 × Z5 family symmetry, resulting in four soft scalar masses at the GUT scale: one left-handed soft mass m0 and three right-handed soft masses m1, m2, m3, one for each generation. We demonstrate that this model, which was initially developed to describe the neutrino sector, can explain collider and non-collider measurements such as the dark matter relic density, the Higgs boson mass and, in particular, the anomalous magnetic moment of the muon (g − 2)μ. Since about two decades, (g − 2)μ suffers a puzzling about 3σ excessoftheexperimentallymeasuredvalueoverthetheoreticalprediction,whichour model is able to fully resolve. As the consequence of this resolution, our model predicts specific regions of the parameter space with the specific properties including light smuons and neutralinos, which could also potentially explain di-lepton excesses observed by CMS and ATLAS

Precision cancer monitoring using a novel, fully integrated, microfluidic array partitioning digital PCR platform.

A novel digital PCR (dPCR) platform combining off-the-shelf reagents, a micro-molded plastic microfluidic consumable with a fully integrated single dPCR instrument was developed to address the needs for routine clinical diagnostics. This new platform offers a simplified workflow that enables: rapid time-to-answer; low potential for cross contamination; minimal sample waste; all within a single integrated instrument. Here we showcase the capability of this fully integrated platform to detect and quantify non-small cell lung carcinoma (NSCLC) rare genetic mutants (EGFR T790M) with precision cell-free DNA (cfDNA) standards. Next, we validated the platform with an established chronic myeloid leukemia (CML) fusion gene (BCR-ABL1) assay down to 0.01% mutant allele frequency to highlight the platform's utility for precision cancer monitoring. Thirdly, using a juvenile myelomonocytic leukemia (JMML) patient-specific assay we demonstrate the ability to precisely track an individual cancer patient's response to therapy and show the patient's achievement of complete molecular remission. These three applications highlight the flexibility and utility of this novel fully integrated dPCR platform that has the potential to transform personalized medicine for cancer recurrence monitoring

Clinical handover within the emergency care pathway and the potential risks of clinical handover failure (ECHO) : primary research

Background and objectives: Handover and communication failures are a recognised threat to patient safety. Handover in emergency care is a particularly vulnerable activity owing to the high-risk context and overcrowded conditions. In addition, handover frequently takes place across the boundaries of organisations that have different goals and motivations, and that exhibit different local cultures and behaviours. This study aimed to explore the risks associated with handover failure in the emergency care pathway, and to identify organisational factors that impact on the quality of handover. Methods: Three NHS emergency care pathways were studied. The study used a qualitative design. Risks were explored in nine focus group-based risk analysis sessions using failure mode and effects analysis (FMEA). A total of 270 handovers between ambulance and the emergency department (ED), and the ED and acute medicine were audio-recorded, transcribed and analysed using conversation analysis. Organisational factors were explored through thematic analysis of semistructured interviews with a purposive convenience sample of 39 staff across the three pathways. Results: Handover can serve different functions, such as management of capacity and demand, transfer of responsibility and delegation of aspects of care, communication of different types of information, and the prioritisation of patients or highlighting of specific aspects of their care. Many of the identified handover failure modes are linked causally to capacity and patient flow issues. Across the sites, resuscitation handovers lasted between 38 seconds and 4 minutes, handovers for patients with major injuries lasted between 30 seconds and 6 minutes, and referrals to acute medicine lasted between 1 minute and approximately 7 minutes. Only between 1.5% and 5% of handover communication content related to the communication of social issues. Interview participants described a range of tensions inherent in handover that require dynamic trade-offs. These are related to documentation, the verbal communication, the transfer of responsibility and the different goals and motivations that a handover may serve. Participants also described the management of flow of patients and of information across organisational boundaries as one of the most important factors influencing the quality of handover. This includes management of patient flows in and out of departments, the influence of time-related performance targets, and the collaboration between organisations and departments. The two themes are related. The management of patient flow influences the way trade-offs around inner tensions are made, and, on the other hand, one of the goals of handover is ensuring adequate management of patient flows. Conclusions: The research findings suggest that handover should be understood as a sociotechnical activity embedded in clinical and organisational practice. Capacity, patient flow and national targets, and the quality of handover are intricately related, and should be addressed together. Improvement efforts should focus on providing practitioners with flexibility to make trade-offs in order to resolve tensions inherent in handover. Collaborative holistic system analysis and greater cultural awareness and collaboration across organisations should be pursued

Upland Habitat Quality and Historic Landscape Composition Influence Genetic Variation of a Pond-Breeding Salamander

Understanding the temporal and spatial scale at which habitat alteration impacts populations is important for conservation and management. Amphibians have declined more than other vertebrates, and pond-breeding species are particularly susceptible to habitat loss and fragmentation because they have terrestrial and aquatic life stages. One approach to management of pond-breeding species is protection of core upland habitat surrounding the breeding pond. We used genetic variation as an indicator of population status in a common amphibian species, spotted salamanders (Ambystoma maculatum), to determine how amount of suitable upland habitat relates to population status in the greater Charlotte, North Carolina, USA metropolitan area. We developed candidate models to evaluate the relative influence of historical and contemporary forested habitat availability on population genetic variation at two spatial scales of upland area (164 m and 2000 m) at four time intervals over the past seven decades (1938, 1978, 1993, 2005). We found that historical land cover best predicted contemporary allelic richness. Inbreeding coefficient and observed heterozygosity were not effectively predicted by forest cover at either spatial or temporal scales. Allelic richness was best predicted at the smaller spatial scale in the 1993 time interval. Predicting and understanding how future landscape configuration affects genetic variation of common and rare species is imperative for the conservation of amphibian and other wildlife populations

Glaciers and small ice caps in the macro-scale hydrological cycle: an assessment of present conditions and future changes

Glacier and small ice cap melt water contributions to the global hydrologic cycle are an important component of human water supply and for sea level rise. This melt water is used in many arid and semi-arid parts of the world for direct human consumption as well as indirect consumption by irrigation for crops, serving as frozen reservoirs of water that supplement runoff during warm and dry periods of summer when it is needed the most. Additionally, this melt water reaching the oceans represents a direct input to sea level rise and therefore accurate estimates of this contribution have profound economic and geopolitical implications. It has been demonstrated that, on the scale of glacierized river catchments, land surface hydrological models can successfully simulate glacier contribution to streamflow. However, at global scales, the implementation of glacier melt in hydrological models has been rudimentary or non-existent. In this study, a global glacier mass balance model is coupled with the University of New Hampshire Water Balance/Transport Model (WBM) to assess recent and projected future glacier contributions to the hydrological cycle over the global land surface (excluding the ice sheets of Greenland and Antarctica). For instance, results of WBM simulations indicate that seasonal glacier melt water in many arid climate watersheds comprises 40 % or more of their discharge. Implicitly coupled glacier and WBM models compute monthly glacier mass changes and resulting runoff at the glacier terminus for each individual glacier from the globally complete Randolph Glacier Inventory including over 200 000 glaciers. The time series of glacier runoff is aggregated over each hydrological modeling unit and delivered to the hydrological model for routing downstream and mixing with non-glacial contribution of runoff to each drainage basin outlet. WBM tracks and uses glacial and non-glacial components of the in-stream water for filling reservoirs, transfers of water between drainage basins (inter-basin hydrological transfers), and irrigation along the global system of rivers with net discharge to the ocean. Climate scenarios from global climate models prepared for IPCC AR5 are used to explore an expected range of possible future glacier outflow variability to estimate the impacts on human use of these valuable waters and their poorly understood net contribution to sea level change

Evidence of HIV exposure and transient seroreactivity in archived HIV-negative severe hemophiliac sera

BACKGROUND: Approximately 25% of hemophiliacs that were frequently exposed to blood clotting factor concentrates (CFCs) contaminated with human immunodeficiency virus (HIV) are presently HIV seronegative. In this study, we sought to determine if some of these individuals were at any time transiently HIV seropositive. In the early to mid-1980s the majority of severe hemophilia patients were exposed to CFCs contaminated with HIV. Although many of these hemophiliacs became HIV-positive, a small percentage did not become infected. To determine if some of these individuals successfully resisted viral infection, we attempted to document the presence of transient HIV reactive antibodies in archived plasma samples (1980–1992) from currently HIV-negative severe hemophiliacs who had a high probability of repeated exposure to HIV contaminated CFC. Archived plasma samples were retrospectively tested using an FDA approved HIV-1Ab HIV-1/HIV-2 (rDNA) enzyme immunoassay (EIA) and a HIV-1 Western blot assay (Wb), neither of which were commercially available until the late 1980s, which was after many of these samples had been drawn. RESULTS: We found that during the high risk years of exposure to HIV contaminated CFC (1980–1987), low levels of plasma antibodies reactive with HIV proteins were detectable in 87% (13/15) of the haemophiliacs tested. None of these individuals are presently positive for HIV proviral DNA as assessed by polymerase chain reaction (PCR). CONCLUSION: Our data suggest that some severe hemophiliacs with heavy exposure to infectious HIV contaminated CFC had only transient low-level humoral immune responses reactive with HIV antigens yet remained HIV-negative and apparently uninfected. Our data supports the possibility of HIV exposure without sustained infection and the existence of HIV-natural resistance in some individuals

Impact of EMA regulatory label changes on systemic diclofenac initiation, discontinuation, and switching to other pain medicines in Scotland, England, Denmark, and The Netherlands

Purpose: In June 2013 a European Medicines Agency referral procedure concluded that diclofenac was associated with an elevated risk of acute cardiovascular events and contraindications, warnings, and changes to the product information were implemented across the European Union. This study measured the impact of the regulatory action on the prescribing of systemic diclofenac in Denmark, The Netherlands, England, and Scotland. Methods: Quarterly time series analyses measuring diclofenac prescription initiation, discontinuation and switching to other systemic nonsteroidal anti-inflammatory (NSAIDs), topical NSAIDs, paracetamol, opioids, and other chronic pain medication in those who discontinued diclofenac. Absolute effects were estimated using interrupted time series regression. Results: Overall, diclofenac prescription initiations fell during the observation periods of all countries. Compared with Denmark where there appeared to be amore limited effect, the regulatory action was associated with significant immediate reductions in diclofenac initiation in The Netherlands (−0.42%, 95% CI, −0.66% to −0.18%), England (−0.09%, 95% CI, −0.11% to −0.08%), and Scotland (−0.67%, 95% CI, −0.79% to −0.55%); and falling trends in diclofenac initiation in the Netherlands (−0.03%, 95% CI, −0.06% to −0.01% per quarter) and Scotland (−0.04%, 95% CI, −0.05% to −0.02% per quarter). There was no significant impact on diclofenac discontinuation in any country. The regulatory action was associated with modest differences in switching to other pain medicines following diclofenac discontinuation. Conclusions: The regulatory action was associated with significant reductions in overall diclofenac initiation which varied by country and type of exposure. There was no impact on discontinuation and variable impact on switching