Agencies in Transition: A Report on the Views of the Members of the Federal Senior Executive Service

Many think of leadership transition in government as something that happens only once every four or eight years. While presidential transitions are undoubtedly the largest in scope, leadership transition in government is a constant process. In fact, the average tenure of Senate-confirmed appointees is only 3.3 years, while appointees at executive departments generally spend only 2.8 years in a single post.In a federal government made up of departments and agencies as large and complex as any Fortune 500 company, a strong leadership team is critical to effective governance. Members of the Senior Executive Service (SES) serve as the primary link between political appointees and the broader federal workforce, operating and overseeing nearly every government activity. They play a significant role during leadership transitions, ensuring the continuity of operations within government. Members of the SES are also uniquely positioned to help incoming political leaders build on the positive reforms of the past, and provide insight from lessons learned that can inform success in the future.The National Academy saw the 2008 Presidential transition as an opportunity to draw upon the experience of the SES to find ways to strengthen the partnerships between political and career leaders and build a more efficient and effective government. The results of our study reinforced the critical role played by members of the SES, and revealed that the majority of these career leaders, though experienced in government, were relatively new to managing transition issues as executives.Key FindingsThe findings demonstrated that despite the newness of presidential transitions for most SES, they have a clear understanding about the role they must play in assisting new political appointees, the importance of forming an effective partnership, and their role in the process. At the same time, they wanted help to prepare for those roles, and were eager to engage in training and other activities that would promote success. These SES preferred to receive assistance in preparing for the transition through: (1) policy briefings; (2) discussions with their peers; (3) written materials; and (4) attendance at seminars or training sessions

Why do people choose nephrology? Identifying positive motivators to aid recruitment and retention

Increasing concerns about recruitment and retention of junior doctors have led to renewed interest in how and when trainees choose their specialties. To our knowledge, no study has yet reported what attracts UK applicants to nephrology nor how clinicians develop vocational interests or make occupational choices. With this in mind, we sought to explore the motivation behind current nephrologist's career choices in the UK. We interviewed 11 nephrologists using a semi-structured face-to-face approach and used interpretative phenomenological analysis to conduct and analyse the interviews. We found role models were pivotal in encouraging specialization in nephrology, particularly those encountered in early postgraduate training. The diversity, diagnostic challenge and cross-specialty knowledge was highlighted as well as the ability to 'make a difference to patients' lives'. Nephrologists enjoyed the challenge of managing very sick, acutely unwell patients as well as the holistic continuity of long-term care offered to dialysis patients and their families. Academic and procedural components were attractive motivators to the specialty and the flexibility to have multiple interests was noted, with many nephrologists having 'portfolio' careers. Based on these results, we suggest strategies the specialty can use to aid policy decision making, promote recruitment and improve educational experiences within current training programmes

Streptomycin-induced inflammation enhances Escherichia coli gut colonization through nitrate respiration.

UnlabelledTreatment with streptomycin enhances the growth of human commensal Escherichia coli isolates in the mouse intestine, suggesting that the resident microbial community (microbiota) can inhibit the growth of invading microbes, a phenomenon known as "colonization resistance." However, the precise mechanisms by which streptomycin treatment lowers colonization resistance remain obscure. Here we show that streptomycin treatment rendered mice more susceptible to the development of chemically induced colitis, raising the possibility that the antibiotic might lower colonization resistance by changing mucosal immune responses rather than by preventing microbe-microbe interactions. Investigation of the underlying mechanism revealed a mild inflammatory infiltrate in the cecal mucosa of streptomycin-treated mice, which was accompanied by elevated expression of Nos2, the gene that encodes inducible nitric oxide synthase. In turn, this inflammatory response enhanced the luminal growth of E. coli by nitrate respiration in a Nos2-dependent fashion. These data identify low-level intestinal inflammation as one of the factors responsible for the loss of resistance to E. coli colonization after streptomycin treatment.ImportanceOur intestine is host to a complex microbial community that confers benefits by educating the immune system and providing niche protection. Perturbation of intestinal communities by streptomycin treatment lowers "colonization resistance" through unknown mechanisms. Here we show that streptomycin increases the inflammatory tone of the intestinal mucosa, thereby making the bowel more susceptible to dextran sulfate sodium treatment and boosting the Nos2-dependent growth of commensal Escherichia coli by nitrate respiration. These data point to the generation of alternative electron acceptors as a by-product of the inflammatory host response as an important factor responsible for lowering resistance to colonization by facultative anaerobic bacteria such as E. coli

What is the initiation step of the Grubbs-Hoveyda olefin metathesis catalyst?

Density function theory calculations reveal that the Grubbs-Hoveyda olefin metathesis pre-catalyst is activated by the formation of a complex in which the incoming alkene substrate and outgoing alkoxy ligand are both clearly associated with the ruthenium centre. The computed energies for reaction are in good agreement with the experimental values, reported here

Experimental Study of Load Carrying Capacity of Point Contacts at Zero Entrainment Velocity

A capacitance technique was used to monitor the film thickness separating two steel balls while subjecting the ball-ball contact to highly stressed, zero entrainment velocity conditions. Tests were performed in a nitrogen atmosphere and utilized 52100 steel balls and a polyalphaolefin lubricant. Capacitance to film thickness accuracy was verified under pure rolling conditions using established EHL theory. Zero entrainment velocity tests were performed at sliding speeds from 6.0 to 10.0 m/s and for sustained amounts of time to 28.8 min. The protective lubricant film separating the specimens at zero entrainment velocity had a film thickness between 0.10 to 0.14 microns (4 to 6 micro in.), which corresponded to a k value of 4. The formation of an immobile surface film formed by lubricant entrapment is discussed as an explanation of the load carrying capacity at zero entrainment velocity conditions, relevant to the ball-ball contacts occurring in retainerless ball bearings

Stressful Life Events During Pregnancy and Offspring Depression: Evidence From a Prospective Cohort Study

Objective The fetal programming hypothesis posits that in utero exposure to stress can alter prenatal brain development and lifelong stress response. However, human studies linking objective prenatal stressors to offspring mental illness, especially depression, are rare. The purpose of this study was to examine the association between mothers’ exposure to prenatal stressful life events (SLEs) and offspring depression. Method The sample comprised 10,569 members of a prospective population-based cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC). Mothers reported on the occurrence and impact of 42 prenatal SLEs. Offspring depressive symptoms were assessed using a computerized version of the Clinical Interview Schedule−Revised (CIS-R) at age 17 to 18, as well as 13 self-report statements from the Short Mood and Feelings Questionnaire (SMFQ) at 6 time points from ages 10 to 11 to 18 to 19. Latent class growth analysis (LCGA) was used to identify trajectories of depressive symptoms across adolescence. Results After adjusting for potential confounders, a 1-unit increase in maternal SLE scores (range, 0–168) during gestation was associated with increased offspring depressive symptoms (β = 0.07, p < .01) and major depression (odds ratio [OR] = 1.03, 95% CI 1.01, 1.06) at age 17 to 18. LCGA revealed 4 trajectories of depressive symptoms. High maternal SLEs (fourth quartile) were associated with membership in the trajectory characterized by stable, high levels of depression from age 10 to 11 to 18 to 19 years (OR = 1.72, 95% CI = 1.09, 2.71). Conclusion These results provide support for the fetal programming hypothesis, demonstrating that prenatal exposure to acute stress is associated with offspring depression in adolescence. Stress management may be of benefit for expectant mothers

Toward a simulation approach for alkene ring-closing metathesis : scope and limitations of a model for RCM

A published model for revealing solvent effects on the ring-closing metathesis (RCM) reaction of di-Et diallylmalonate 7 has been evaluated over a wider range of conditions, to assess its suitability for new applications. Unfortunately, the model is too flexible and the published rate consts. do not agree with exptl. studies in the literature. However, by fixing the values of important rate consts. and restricting the concn. ranges studied, useful conclusions can be drawn about the relative rates of RCM of different substrates, precatalyst concn. can be simulated accurately and the effect of precatalyst loading can be anticipated. Progress has also been made toward applying the model to precatalyst evaluation, but further modifications to the model are necessary to achieve much broader aims

Towards UK poSt Arthroplasty Follow-up rEcommendations (UK SAFE): protocol for an evaluation of the requirements for arthroplasty follow-up, and the production of consensus-based recommendations

Introduction: Hip and knee arthroplasties have revolutionised the management of degenerative joint diseases and, due to an ageing population, are becoming increasingly common. Follow-up of joint prostheses is to identify problems in symptomatic or asymptomatic patients due to infection, osteolysis, bone loss or potential peri-prosthetic fracture, enabling timely intervention to prevent catastrophic failure at a later date. Early revision is usually more straight-forward surgically and less traumatic for the patient. However, routine long-term follow-up is costly and requires considerable clinical time. Therefore, some centres in the UK have curtailed this aspect of primary hip and knee arthroplasty services, doing so without an evidence-base that such disinvestment is clinically- or cost-effective. Methods: Given the timeline from joint replacement to revision, conducting a randomised controlled trial (RCT) to determine potential consequences of disinvestment in hip and knee arthroplasty follow-up is not feasible. Furthermore the low revision rates of modern prostheses, less than 10% at 10 years, would necessitate thousands of patients to adequately power such a study. The huge variation in follow-up practice across the UK also limits the generalisability of an RCT. This study will therefore use a mixed-methods approach to examine the requirements for arthroplasty follow-up and produce evidence- and consensus-based recommendations as to how, when and on whom follow-up should be conducted. Four interconnected work packages will be completed: 1) a systematic literature review; 2a) analysis of routinely-collected NHS data from five national datasets to understand when and which patients present for revision surgery; 2b) prospective data regarding how patients currently present for revision surgery; 3) economic modelling to simulate long-term costs and quality-adjusted life years associated with different follow-up care models; 4) a Delphi-consensus process, involving all stakeholders, to develop a policy document which includes a stratification algorithm to determine appropriate follow-up care for an individual patient

Evaluating the effectiveness of land use management as a natural flood management intervention in reducing the impact of flooding for an upland catchment

Natural flood management (NFM) is a method for reducing flooding by using a catchment-based approach to managing flood risk. Understanding and quantifying the impact of implementing NFM at the catchment scale remains ambiguous with a clear need for robust empirical evidence. A combination of fieldwork, laboratory analysis and modelling was applied to quantify the impacts of land use management changes on catchment flood hazard. Soil hydraulic conductivity was measured under varying land management regimes and used to parameterize a physically based spatially distributed hydrological model (SD-TOPMODEL). A suite of stakeholder informed land management scenarios was modelled, permitting the quantification of the impact of NFM interventions on the timing and the intensity of the peak discharge at the catchment outlet. The findings support the implementation of NFM interventions as a means of reducing flood hazard within a rural upland catchment. Improved soil infiltration provided the greatest reduction in the intensity and delayed timing of the flood peak for a 10-year occurrence storm event (7% reduction in peak runoff and 8% increase in lag time) with similar reductions observed for a 100-year storm event. Catchment wide woodland planting reduced peak flow by 11% during the 100-year event but was not effective during the 10-year event. Riparian buffer strips provided consistent reductions in peak flow and in the timing of the peak across both storm events with no significant differences relating to vegetation age. Critically, we observed that the effect of implementing multiple NFM interventions was not additive and that efficiencies can be made in using this modelling approach to prioritize the most effective outcomes

Base resolution maps reveal the importance of 5-hydroxymethylcytosine in a human glioblastoma

Aberrant genetic and epigenetic variations drive malignant transformation and are hallmarks of cancer. Using PCR-free sample preparation we achieved the first in-depth whole genome (hydroxyl)-methylcytosine, single-base-resolution maps from a glioblastoma tumour/margin sample of a patient. Our data provide new insights into how genetic and epigenetic variations are interrelated. In the tumour, global hypermethylation with a depletion of 5-hydroxymethylcytosine was observed. The majority of single nucleotide variations were identified as cytosine-to-thymine deamination products within CpG context, where cytosine was preferentially methylated in the margin. Notably, we observe that cells neighbouring tumour cells display epigenetic alterations characteristic of the tumour itself although genetically they appear “normal”. This shows the potential transfer of epigenetic information between cells that contributes to the intratumour heterogeneity of glioblastoma. Together, our reference (epi)-genome provides a human model system for future studies that aim to explore the link between genetic and epigenetic variations in cancer progression.Cancer Research UK 236 (Grant ID: C14303/A17197), Wellcome Trust (Grant ID: 099232/z/12/z