The Impact of State Fiscal Policy on States\u27 Resilience Entering the Great Recession

The U.S. economy entered the Great Recession in December 2007 and exited in June 2009. This national statistic obscures a wealth of state-level data shedding light on the policies and conditions that helped some states withstand that recessionary shock for a time. In this study, we used that state-level data in a parametric regression model, known as survival analysis, to estimate the effects that a state’s fiscal policy had on the timing of its entry into the Great Recession. Consistent with earlier, more general, studies focusing on economic growth, we found that taxes have the potential to hasten the start of a state’s recession, while expenditures could defer that event. However, not all types of taxes and expenditures were equivalent in terms of their effect on recessionary timing. Most notably, our results showed that corporate income taxes had a different timing effect than sales, property, and individual income taxes. In addition, although total expenditures tended to delay the Great Recession’s onset, relatively few individual expenditure types had a statistically-significant impact on recessionary timing. Overall, our results suggest that, while taxes likely increase a state’s recessionary risk and expenditures likely decrease it, that narrative is an oversimplification of the complex role played by fiscal policy in determining a state\u27s ability to resist a negative economic shock like the Great Recession

Inhibitory feedback control of NF-κB signalling in health and disease.

Cells must adapt to changes in their environment to maintain cell, tissue and organismal integrity in the face of mechanical, chemical or microbiological stress. Nuclear factor-κB (NF-κB) is one of the most important transcription factors that controls inducible gene expression as cells attempt to restore homeostasis. It plays critical roles in the immune system, from acute inflammation to the development of secondary lymphoid organs, and also has roles in cell survival, proliferation and differentiation. Given its role in such critical processes, NF-κB signalling must be subject to strict spatiotemporal control to ensure measured and context-specific cellular responses. Indeed, deregulation of NF-κB signalling can result in debilitating and even lethal inflammation and also underpins some forms of cancer. In this review, we describe the homeostatic feedback mechanisms that limit and 're-set' inducible activation of NF-κB. We first describe the key components of the signalling pathways leading to activation of NF-κB, including the prominent role of protein phosphorylation and protein ubiquitylation, before briefly introducing the key features of feedback control mechanisms. We then describe the array of negative feedback loops targeting different components of the NF-κB signalling cascade including controls at the receptor level, post-receptor signalosome complexes, direct regulation of the critical 'inhibitor of κB kinases' (IKKs) and inhibitory feedforward regulation of NF-κB-dependent transcriptional responses. We also review post-transcriptional feedback controls affecting RNA stability and translation. Finally, we describe the deregulation of these feedback controls in human disease and consider how feedback may be a challenge to the efficacy of inhibitors

Ordinary Soldiers: A Study in Ethics, Law and Leadership

Ordinary Soldiers uses a World War II case study as the basis for educating, training, and inspiring current and future officers through critical consideration of leadership and ethics. The resource prompts discussion of the legal and ethical standards U.S. military professionals are expected to meet, the challenges military leaders face in making consistently legal decisions in a combat theater, and the consequences of failure to meet these standards. Ordinary Soldiers has been designed in a modular format that can be adapted depending upon time available, lesson objectives, and class sizes ranging from just a few students to nearly 100. It is used at military academies, by the Reserve Officer Training Corps, and in other professional military education venues

Validation of the foot profile score

Background: There are numerous static measures of foot posture but there is no published score of dynamic foot motion. Three-dimensional gait analysis can include a multi-segment foot model like the Oxford Foot Model (OFM) to comprehensively quantify foot kinematic deviations across the gait cycle but it lacks an overall score, like the Gait Profile score (GPS), used to summarize the quality of lower extremity motion. Research question: This paper introduces the Foot Profile Score (FPS), a single number, analogous to the GPS but based on kinematic data of the OFM. The aim of this study is to validate the FPS by studying its properties and design, and analyse it against a clinical assessment of foot deformity. Methods: Concurrent validity was established for the FPS analysing the relationship with Clinical Foot Deformity Score (CFDS) in 60 subjects with a condition affecting the lower limbs globally Content validity was established for the six Foot Variable Scores (FVS) that make up the FPS using a multiple regression of the CFDS on the 6 FVS in the 60 subjects. Predictive validity was established analysing the relationship of the FPS and GPS comparing 60 global involvement subjects with 60 subjects with isolated foot deformity. Results: Pearson correlation between the FPS and CFDS was significant at 0.62 (p &lt; 0.001). Each element of FVS contributes positively to predicting the CFDS with R2 = 0.456 (p &lt; 0.001). FPS contributed independently to the prediction of CFDS (t = 3.9, p &lt; 0.001). The correlation between the GPS and FPS in the global involvement group was significant at r = 0.64 (p &lt; 0.001), while there was no correlation found with r = 0.08 (p = 0.54) in the foot deformity group. Significance: The FPS is the first validated score of dynamic foot motion.</p

Relationship between sociodemographic factors and specialty destination of UK trainee doctors:a national cohort study

We are grateful to UKMED for releasing the data for this project. We also are grateful to the following for their support of the application to UKMED for this and other research projects: Dr Sally Curtis (University of Southampton, UK), Dr Sandra Nicholson (Barts and The London School of Medicine and Dentistry, UK). We thank Daniel Smith and Andy Knapton of the General Medical Council of the UK for their support for the application and throughout the project, particularly regarding data linkage and troubleshooting.Peer reviewedPublisher PD

Subcutaneous Immunoglobulin Replacement Therapy with Hizentra® is Safe and Effective in Children Less Than 5 Years of Age.

BACKGROUND:Hizentra® (IGSC 20%) is a 20% liquid IgG product approved for subcutaneous administration in adults and children 2 years of age and older who have primary immunodeficiency disease (PIDD). There is limited information about the use of IGSC 20 % in very young children including those less than 5 years of age. METHODS:A retrospective chart review involved 88 PIDD infants and children less than 5 years of age who received Hizentra®. RESULTS:The mean age at the start of Hizentra® was 34 months (range 2 to 59 months). IGSC 20 % was administered weekly to 86 infants (two additional infants received twice weekly and three times weekly infusions, respectively) and included an average of 63 infusions (range 6-182) for an observation period up to 45.5 months. Infusion by manual delivery occurred in 15 patients. The mean dose was 674 mg/kg/4 weeks. The mean IgG level was 942 mg/dL while on IGSC 20 %, compared to a mean trough IgG level of 794 mg/dL (p &lt; 0.0001) during intravenous or subcutaneous IgG administration prior to IGSC 20 %. Average infusion time was 47 (range 5-120) minutes, and the median number of infusion sites was 2 (range 1-4). Local reactions were mostly mild and observed in 36/88 (41%) children. No serious adverse events were reported. A significant increase in weight percentile (7 % ± 19.2, p = 0.0012) among subjects was observed during IGSC 20% administration. The rate of serious bacterial infections was 0.067 per patient-year while receiving IGSC 20%, similar to previously reported efficacy studies. CONCLUSIONS:Hizentra® is effective in preventing infections, and is well tolerated in children less than age 5 years

Surrogates of Long-Term Vitamin D Exposure and Ovarian Cancer Risk in Two Prospective Cohort Studies

Experimental evidence and ecologic studies suggest a protective role of vitamin D in ovarian carcinogenesis. However, epidemiologic studies using individual level data have been inconsistent. We evaluated ultraviolet (UV)-B radiation, vitamin D intake, and predicted plasma 25-hydroxyvitamin D [25(OH)D] levels as long-term surrogates of vitamin D exposure within the Nurses’ Health Study (NHS) and NHSII. We estimated incidence rate ratios (RRs) and 95% confidence intervals (CIs) for risk of overall ovarian cancer and by histologic subtype using Cox proportional hazards models. Between 1976 and 2010 in NHS and 1989 and 2011 in NHSII, we identified a total of 1,225 incident epithelial ovarian cancer cases (NHS: 970, NHSII: 255) over 4,628,648 person-years of follow-up. Cumulative average UV-B exposure was not associated with ovarian cancer risk in NHS (Ptrend = 0.08), but was associated with reduced risk in NHSII (highest vs. lowest category RR = 0.67; 95% CI: 0.50, 0.89; Ptrend < 0.01). When stratified by histologic subtype, UV-B flux was positively associated with risk of serous tumors in NHS (Ptrend < 0.01), but inversely associated in NHSII (Ptrend = 0.01). Adjusted for confounders, ovarian cancer risk was not associated with vitamin D intake from food or supplements or with predicted 25(OH)D levels. Our study does not strongly support a protective role for vitamin D in ovarian cancer risk

Evidence of Differential Effects of Vitamin D Receptor Variants on Epithelial Ovarian Cancer Risk by Predicted Vitamin D Status

Introduction: Experimental studies suggest vitamin D inhibits ovarian carcinogenesis. Yet, epidemiologic studies of ovarian cancer risk and lifestyle correlates of vitamin D status, plasma 25-hydroxyvitamin D [25(OH)D], or vitamin D receptor (VDR) variants have been inconsistent. Objective: To evaluate VDR genetic associations by high vs. low predicted 25(OH)D, scores derived from known determinants of plasma 25(OH)D. To assess ovarian cancer associations with variants identified in genome-wide association studies (GWAS) of plasma 25(OH)D. Methods: We genotyped up to seven VDR and eight 25(OH)D GWAS variants in the Nurses’ Health Studies (562 cases, 1,553 controls) and New England Case–Control study (1,821 cases, 1,870 controls). We estimated haplotype scores using expectation-maximization-based algorithms. We used unconditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CI). We combined study results using DerSimonian and Laird meta-analysis. Results: Ovarian cancer risk increased per A allele of rs7975232 (VDR; OR = 1.12, 95% CI = 1.01–1.25) among all women. When stratified by predicted 25(OH)D, ovarian cancer was associated with rs731236 (VDR; per C allele OR = 1.31) and rs7975232 (OR = 1.38) among women with high predicted 25(OH)D, but not among women with low levels (P ≤ 0.009). We also observed heterogeneity by predicted 25(OH)D for the ovarian cancer association with VDR 3′ end haplotypes (P = 0.009). Of 25(OH)D-associated GWAS loci, rs7041 was associated with reduced ovarian cancer risk (per T allele OR = 0.92, 95% CI = 0.85-0.99), which did not differ by predicted 25(OH)D status. Conclusion: Our study suggests an influence of VDR 3′ end variants on ovarian cancer risk may be observed in women with high predicted 25(OH)D, which remained even after taking multiple comparisons into consideration. Future studies are needed to confirm our results and explore further the relation between vitamin D exposure, genetic variants, and ovarian cancer risk

High Phobic Anxiety Is Related to Lower Leukocyte Telomere Length in Women

Background: Chronic psychological distress has been linked to shorter telomeres, an indication of accelerated aging. Yet, little is known about relations of anxiety to telomeres. We examined whether a typically chronic form of anxiety – phobic anxiety – is related to telomere length. Methodology/Principal Findings Relative telomere lengths (RTLs) in peripheral blood leukocytes were measured by quantitative real-time polymerase chain reaction among 5,243 women (aged 42–69 years) who: were participants in the Nurses' Health Study; were controls in prior case-control studies of telomeres and disease, or randomly selected healthy participants in a cognitive function sub-study; had completed the Crown-Crisp phobic index proximal to blood collection. Adjusted least-squares mean RTLs (z-scores) were calculated across phobic categories. Higher phobic anxiety was generally associated with lower RTLs (age-adjusted p-trend = 0.09); this association was similar after adjustment for confounders – paternal age-at-birth, smoking, body mass index (BMI) and physical activity (p-trend = 0.15). Notably, a threshold was identified. Among women with Crown-Crisp<6 points, the multivariable-adjusted least-squares mean RTL z-score = 0.02 standard units; however, among the most phobic women (Crown-Crisp≥6), the multivariable-adjusted least-squares mean RTL z-score = −0.09 standard units (mean difference = −0.10 standard units; p = 0.02). The magnitude of this difference was comparable to that for women 6 years apart in age. Finally, effect modification by BMI, smoking and paternal age was observed: associations were stronger among highly phobic women with BMI≥25 kg/m2, without smoking history, or born to fathers aged ≥40 years. Conclusions/Significance: In this large, cross-sectional study high phobic anxiety was associated with shorter telomeres. These results point toward prospective investigations relating anxiety to telomere length change

Genetic Predisposition to Higher Body Mass Index or Type 2 Diabetes and Leukocyte Telomere Length in the Nurses' Health Study

Background: Although cross-sectional studies have linked higher body mass index (BMI) and type 2 diabetes (T2D) to shortened telomeres, whether these metabolic conditions play a causal role in telomere biology is unknown. We therefore examined whether genetic predisposition to higher BMI or T2D was associated with shortened leukocyte telomere length (LTL). Methodology: We conducted an analysis of 3,968 women of European ancestry aged 43–70 years from the Nurses' Health Study, who were selected as cases or controls in genome-wide association studies and studies of telomeres and disease. Pre-diagnostic relative telomere length in peripheral blood leukocytes, collected in 1989–1990, was measured by quantitative PCR. We combined information from multiple risk variants by calculating genetic risk scores based on 32 polymorphisms near 32 loci for BMI, and 36 polymorphisms near 35 loci for T2D. Findings: After adjustment for age and case-control status, there was no association between the BMI genetic risk score and LTL (β per standard deviation increase: −0.01; SE: 0.02; P = 0.52). Similarly, the T2D genetic score was not associated with LTL (β per standard deviation increase: −0.006; SE: 0.02; P = 0.69). Conclusions: In this population of middle-aged and older women of European ancestry, those genetically predisposed to higher BMI or T2D did not possess shortened telomeres. Although we cannot exclude weak or modest effects, our findings do not support a causal relation of strong magnitude between these metabolic conditions and telomere dynamics