Cell coupling compensates for changes in single-cell Her6 dynamics and provides phenotypic robustness.

We investigate the effect of altering the protein expression dynamics of the bHLH transcription factor Her6 at the single-cell level in the embryonic zebrafish telencephalon. Using an homozygote endogenous Her6:Venus reporter and 4D single-cell tracking, we show that Her6 oscillates in neural telencephalic progenitors and that fusion of protein destabilisation domain (PEST) alters its expression dynamics, causing most cells to downregulate Her6 prematurely. However, counterintuitively, oscillatory cells increase with some expressing Her6 at high levels, resulting in increased heterogeneity of Her6 expression in the population. These tissue-levels changes appear to be an emergent property of coupling between single-cells as revealed by experimentally disrupting Notch signalling and by computationally modelling alterations in Her6 protein stability. Despite the profound differences in the single-cell Her6 dynamics, the size of the telencephalon is only transiently altered, and differentiation markers do not exhibit significant differences early on, while a small increase is observed at later developmental stages. Our study suggests that cell coupling provides a compensation strategy, whereby an almost normal phenotype is maintained even though single-cell gene expression dynamics are abnormal, granting phenotypic robustness.

Middle-aged adults' career trajectories and later-life financial security: evidence from Korea.

This study explored how middle-aged workers' career trajectory patterns were associated with their financial security later in life. Grounded by a life course perspective, we approached their career trajectories by considering a 'human agency within structure' framework. We explored sequences of employment status, starting with their lifetime main job to subsequent jobs after contractual retirement, using data from 1,010 middle-aged adults in Seoul, South Korea. The sequence analysis identified six career trajectory patterns. Stable career patterns included the Permanent to permanent trajectory as well as the Permanent to self-employment trajectory and these were most common among males with higher education degrees, higher earnings and better career alignment. Unstable career patterns such as the Temporary to temporary trajectory, the Permanent to temporary trajectory or the Churning trajectory were most common among those who were female, had lower levels of education lower earnings or had retired involuntarily. Further results showed that unstable career patterns were associated with lower levels of monthly earnings and total assets post-contractual retirement. Individuals with unstable career patterns were also less likely to be financially prepared for retirement. We suggest individualising education programmes for retirement preparation based on various career trajectories and demographic attributes to aid middle-aged adults in preparing for financial security later in life.

Dynamic switching of lateral inhibition spatial patterns.

Hes genes are transcriptional repressors activated by Notch. In the developing mouse neural tissue, HES5 expression oscillates in neural progenitors (Manning et al. 2019 Nat. Commun. 10, 1-19 (doi:10.1038/s41467-019-10734-8)) and is spatially organized in small clusters of cells with synchronized expression (microclusters). Furthermore, these microclusters are arranged with a spatial periodicity of three-four cells in the dorso-ventral axis and show regular switching between HES5 high/low expression on a longer time scale and larger amplitude than individual temporal oscillators (Biga et al. 2021 Mol. Syst. Biol. 17, e9902 (doi:10.15252/msb.20209902)). However, our initial computational modelling of coupled HES5 could not explain these features of the experimental data. In this study, we provide theoretical results that address these issues with biologically pertinent additions. Here, we report that extending Notch signalling to non-neighbouring progenitor cells is sufficient to generate spatial periodicity of the correct size. In addition, introducing a regular perturbation of Notch signalling by the emerging differentiating cells induces a temporal switching in the spatial pattern, which is longer than an individual cell's periodicity. Thus, with these two new mechanisms, a computational model delivers outputs that closely resemble the complex tissue-level HES5 dynamics. Finally, we predict that such dynamic patterning spreads out differentiation events in space, complementing our previous findings whereby the local synchronization controls the rate of differentiation.

Maintaining School Foodservice Operations in Ohio during COVID-19: "This [Was] Not the Time to Sit Back and Watch".

The COVID-19-related lockdowns led to school closures across the United States, cutting off critical resources for nutritious food. Foodservice employees emerged as frontline workers; understanding their experiences is critical to generate innovations for program operations and viability. The purpose of this cross-sectional study was to characterize COVID-19-related foodservice adaptations for summer and school year meal provision. Public school district foodservice administrators across Ohio were surveyed in December 2020. Questions related to meal provision before, during, and after COVID-19-related school closures. Results indicate the majority of districts continued providing meals upon their closure in Spring 2020 (n = 182, 87.1%); fewer did so in Summer (n = 88, 42.1%) and Fall (n = 32, 15.3%). In Spring and Summer, most districts that offered meals functioned as 'open sites' (67.0% and 87.5%, respectively), not limiting food receipt to district-affiliated students. Most districts employed a pick-up system for food distribution (76-84% across seasons), though some used a combination of approaches or changed their approach within-season. Qualitatively, districts reported both "successes" (e.g., supporting students) and "challenges" (e.g., supply chain). Despite being ill-prepared, districts responded quickly and flexibly to demands of the pandemic. This analysis provides insight for future practice (e.g., establishing community partnerships) and policy (e.g., bolstering local food systems).

A contemporary reassessment of the US surgical workforce through 2050 predicts continued shortages and increased productivity demands.

BACKGROUND: We aimed to predict practicing surgeon workforce size across ten specialties to provide an up-to-date, national perspective on future surgical workforce shortages or surpluses. METHODS: Twenty-one years of AMA Masterfile data (1997-2017) were used to predict surgeons practicing from 2030 to 2050. Published ratios of surgeons/100,000 population were used to estimate the number of surgeons needed. MGMA median wRVU/surgeon by specialty (2017) was used to determine wRVU demand and capacity based on projected and needed number of surgeons. RESULTS: By 2030, surgeon shortages across nine specialties: Cardiothoracic, Otolaryngology, General Surgery, Obstetrics-Gynecology, Ophthalmology, Orthopedics, Plastics, Urology, and Vascular, are estimated to increase clinical workload by 10-50% additional wRVU. By 2050, shortages in eight specialties are estimated to increase clinical workload by 7-61% additional wRVU. CONCLUSIONS: If historical trends continue, a majority of surgical specialties are estimated to experience workforce deficits, increasing clinical demands substantially.

A dynamic, spatially periodic, micro-pattern of HES5 underlies neurogenesis in the mouse spinal cord.

Ultradian oscillations of HES Transcription Factors (TFs) at the single-cell level enable cell state transitions. However, the tissue-level organisation of HES5 dynamics in neurogenesis is unknown. Here, we analyse the expression of HES5 ex vivo in the developing mouse ventral spinal cord and identify microclusters of 4-6 cells with positively correlated HES5 level and ultradian dynamics. These microclusters are spatially periodic along the dorsoventral axis and temporally dynamic, alternating between high and low expression with a supra-ultradian persistence time. We show that Notch signalling is required for temporal dynamics but not the spatial periodicity of HES5. Few Neurogenin 2 cells are observed per cluster, irrespective of high or low state, suggesting that the microcluster organisation of HES5 enables the stable selection of differentiating cells. Computational modelling predicts that different cell coupling strengths underlie the HES5 spatial patterns and rate of differentiation, which is consistent with comparison between the motoneuron and interneuron progenitor domains. Our work shows a previously unrecognised spatiotemporal organisation of neurogenesis, emergent at the tissue level from the synthesis of single-cell dynamics.

The role of education, occupational match on job satisfaction in the behavioral and social science workforce.

While many studies that have been conducted in recent years examining the education and workforce outcomes of STEM graduates, few have focused on the behavioral and social sciences (BSS). Federal agencies, such as National Institutes of Health (NIH), are implementing policies to foster multidisciplinary research in an effort to find more effective solutions to complex problems. As a result, there is growing interest in the career pathways of BSS scientists. This study seeks to increase our understanding of how BSS graduates, particularly women and underrepresented minorities, transition to employment within their respective fields. The focus of this research is the impact of horizontal mismatch, defined as the misalignment between a worker's degree and occupational fields, on job satisfaction and wage outcomes. This analysis of returns to education when mismatch occurs, including a comparison among majors and various demographic groups, provides insights into the labor market experiences of these scientists. Mismatched graduates were found to be much more vulnerable, earning less, and having lower job satisfaction, than their counterparts employed in jobs that aligned with their field of study. Additional job-related training was found to have a positive influence on these outcomes. Also of interest in this study were variations in wage penalties and job satisfaction between groups having different gender and race diversity characteristics. These findings are useful to human resource development (HRD) professionals, governmental policymakers, and other stakeholders seeking strategies to improve the workforce outcomes of BSS scientists.

Recent trends in the U.S. Behavioral and Social Sciences Research (BSSR) workforce.

While behavioral and social sciences occupations comprise one of the largest portions of the "STEM" workforce, most studies of diversity in STEM overlook this population, focusing instead on fields such as biomedical or physical sciences. This study evaluates major demographic trends and productivity in the behavioral and social sciences research (BSSR) workforce in the United States during the past decade. Our analysis shows that the demographic trends for different BSSR fields vary. In terms of gender balance, there is no single trend across all BSSR fields; rather, the problems are field-specific, and disciplines such as economics and political science continue to have more men than women. We also show that all BSSR fields suffer from a lack of racial and ethnic diversity. The BSSR workforce is, in fact, less representative of racial and ethnic minorities than are biomedical sciences or engineering. Moreover, in many BSSR subfields, minorities are less likely to receive funding. We point to various funding distribution patterns across different demographic groups of BSSR scientists, and discuss several policy implications.

A Note on PhD Population Growth in Biomedical Sciences.

The explosive increase in the number of postdocs in biomedical fields is puzzling for many science policymakers. We use our previously introduced parameter in this journal, the basic reproductive number in academia (R0 ), to make sense of PhD population growth in biomedical fields. Our analysis shows how R0 in biomedical fields has increased over time, and we estimate that there is approximately only one tenure-track position in the US for every 6.3 PhD graduates, which means the rest need to get jobs outside academia or stay in lower-paid temporary positions. We elaborate on the structural reasons and systemic flaws of science workforce development by discussing feedback loops, especially vicious cycles, which contribute to over-production of PhDs. We argue that the current system is unstable but with no easy solution. A way to mitigate the effects of strong reinforcing loops is full disclosure of the risks of getting PhD.

Effects of government spending on research workforce development: evidence from biomedical postdoctoral researchers.

We examine effects of government spending on postdoctoral researchers' (postdocs) productivity in biomedical sciences, the largest population of postdocs in the US. We analyze changes in the productivity of postdocs before and after the US government's 1997 decision to increase NIH funding. In the first round of analysis, we find that more government spending has resulted in longer postdoc careers. We see no significant changes in researchers' productivity in terms of publication and conference presentations. However, when the population is segmented by citizenship, we find that the effects are heterogeneous; US citizens stay longer in postdoc positions with no change in publications and, in contrast, international permanent residents (green card holders) produce more conference papers and publications without significant changes in postdoc duration. Possible explanations and policy implications of the analysis are discussed.

Research Workforce Diversity: The Case of Balancing National versus International Postdocs in US Biomedical Research.

The US government has been increasingly supporting postdoctoral training in biomedical sciences to develop the domestic research workforce. However, current trends suggest that mostly international researchers benefit from the funding, many of whom might leave the USA after training. In this paper, we describe a model used to analyse the flow of national versus international researchers into and out of postdoctoral training. We calibrate our model in the case of the USA and successfully replicate the data. We use the model to conduct simulation-based analyses of effects of different policies on the diversity of postdoctoral researchers. Our model shows that capping the duration of postdoctoral careers, a policy proposed previously, favours international postdoctoral researchers. The analysis suggests that the leverage point to help the growth of domestic research workforce is in the pregraduate education area, and many policies implemented at the postgraduate level have minimal or unintended effects on diversity.

Adult-Onset Still's Disease Masquerading as Sepsis in an Asplenic Active Duty Soldier.

This is a case of a 26-year-old active duty male with a history of idiopathic thrombocytopenic purpura (ITP) and surgical asplenia who presented with a one-week history of fevers, myalgias, arthralgias, and rigors. His evaluation upon presentation was significant for a temperature of 103 degrees F, white blood cell count of 36 K with a granulocytic predominance, and elevated transaminases. He was treated empirically with broad-spectrum antibiotics with concern for a systemic infection with an encapsulated organism. During his stay, he developed four SIRS criteria and was transferred to the progressive care unit for suspected sepsis. He continued to have twice-daily fevers and a faint, salmon-colored centripetal rash was eventually observed during his febrile episodes. After a nondiagnostic microbiologic and serologic workup, he was diagnosed with adult-onset Still's Disease and started on intravenous methylprednisolone with brisk response. He was discharged on oral prednisone and was started on anakinra. Adult-onset Still's disease is a rare condition that presents with varying severity, and this is the first reported case, to our knowledge, of its diagnosis in an asplenic patient. Its management in the setting of asplenia is complicated by the need for antibiotic therapy with each episode of fever.

Colistin heteroresistance in acinetobacter and its association with previous colistin therapy.

Colistin heteroresistance has been reported among Acinetobacter isolates; however, its association with prior colistin therapy has not been not described. A population analysis profile identified resistant Acinetobacter subpopulations from colistin-susceptible clinical isolates. The proportion of cells exhibiting heteroresistance was significantly higher among isolates recovered from patients treated with colistin.

Efficacy of caspofungin and posaconazole in a murine model of disseminated Exophiala infection.

Disseminated phaeohyphomycosis is an uncommon infection affecting immunocompetent and immunocompromised individuals in which response to older antifungal agents has been variable. We compared the effect of six days of therapy with caspofungin, posaconazole, and amphotericin B in parallel studies of survival and fungal burden in an immunocompromised mouse model of Exophiala infection. Mice immunocompromised with cyclophosphamide were treated for 6 days starting one day after initiation of infection. Treatment regimens included amphotericin B, caspofungin, and posaconazole. In the survival studies, experimental animals were observed for 14 days. In the fungal burden tests the experimental animals were sacrificed 7 days after infection and brain and kidney burden determined. Treatment with any agent decreased mortality (P < 0.05), with 40%, 30%, and 80% observed survival of the animals treated with amphotericin B, caspofungin, and posaconazole, respectively. Amphotericin B and posaconazole treatment resulted in a decrease in fungal burden compared to untreated controls (P < 0.05). No reduction in fungal burden was noted in the caspofungin group. All three antifungals evaluated improved survival of immunocompromised mice in this otherwise fatal disseminated phaeohyphomycosis. Amphotericin B and posaconazole reduced fungal burden. Posaconazole and caspofungin appear to have potential for use in treatment of this rare infection.

Targeted intranasal mupirocin to prevent colonization and infection by community-associated methicillin-resistant Staphylococcus aureus strains in soldiers: a cluster randomized controlled trial.

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is an emerging pathogen that primarily manifests as uncomplicated skin and soft tissue infections. We conducted a cluster randomized, double-blind, placebo-controlled trial to determine whether targeted intranasal mupirocin therapy in CA-MRSA-colonized soldiers could prevent infection in the treated individual and prevent new colonization and infection within their study groups. We screened 3,447 soldiers comprising 14 training classes for CA-MRSA colonization from January to December 2005. Each training class was randomized to either the mupirocin or placebo study group, and the participants identified as CA-MRSA colonized were treated with either mupirocin or placebo. All participants underwent repeat screening after 8 to 10 weeks and were monitored for 16 weeks for development of infection. Of 3,447 participants screened, 134 (3.9%) were initially colonized with CA-MRSA. Five of 65 (7.7%; 95% confidence interval [95% CI], 4.0% to 11.4%) placebo-treated participants and 7 of 66 (10.6%; 95% CI, 7.9% to 13.3%) mupirocin-treated participants developed infections; the difference in the infection rate of the placebo- and mupirocin-treated groups was -2.9% (95% CI, -7.5% to 1.7%). Of those not initially colonized with CA-MRSA, 63 of 1,459 (4.3%; 95% CI, 2.7% to 5.9%) of the placebo group and 56 of 1,607 (3.5%; 95% CI, 2.6% to 5.2%) of the mupirocin group developed infections; the difference in the infection rate of the placebo and mupirocin groups was 0.8% (95% CI, -1.0% to 2.7%). Of 3,447 participants, 3,066 (89%) were available for the second sampling and completed follow-up. New CA-MRSA colonization occurred in 24 of 1,459 (1.6%; 95% CI, 0.05% to 2.8%) of the placebo group participants and 23 of 1,607 (1.4%; 95% CI, 0.05% to 2.3%) of the mupirocin group participants; the difference in the infection rate of the placebo and mupirocin groups was 0.2% (95% CI, -1.3% to 1.7%). Despite CA-MRSA eradication in colonized participants, this study showed no decrease in infections in either the mupirocin-treated individuals or within their study group. Furthermore, CA-MRSA eradication did not prevent new colonization within the study group.

Efficacy of fluoroquinolones against Leptospira interrogans in a hamster model.

Ciprofloxacin, gatifloxacin, and levofloxacin were evaluated for their abilities to prevent mortality in hamsters infected with a lethal inoculum of Leptospira interrogans serovar Portlandvere. Each agent produced a statistically significant survival advantage compared to no treatment and demonstrated survival similar to that seen with doxycycline therapy.

A case of prostatitis due to Burkholderia pseudomallei.

BACKGROUND: A 67-year-old male, with a history of stable lower urinary tract symptoms, diabetes mellitus, benign prostatic hyperplasia, gonococcal urethritis, and excessive alcohol consumption, presented to the emergency room with sepsis and acute bacterial prostatitis. He had recently returned from a visit to Indonesia, where he had been a first-hand witness to the 2004 tsunami. INVESTIGATIONS: Complete blood cell count, urine analysis, blood, urine, and prostatic abscess cultures, chest X-ray, contrasted CT of the abdomen and pelvis, and (18)F-fluorodeoxyglucose PET. DIAGNOSIS: Melioidosis. MANAGEMENT: Broad-spectrum empiric antibiotics were administered initially; therapy was then changed to intravenous imipenem plus cilastatin with slow initial clinical improvement. (18)F-fluorodeoxyglucose PET localized the prostate as the only nidus of infection. Ultrasound-guided fine needle aspiration of a small fluid collection of the prostate also grew Burkholderia pseudomallei. The patient improved clinically and was discharged to complete a 2-week course of intravenous imipenem plus cilastatin followed by a 3-month course of oral trimethoprim plus sulfamethoxazole. This medication was switched to co-amoxiclav and doxycycline to complete the 3-month course. The patient was well at his last follow-up, 3 months following hospital discharge.