Genetic background influences survival of infections with Salmonella enterica serovar Typhimurium in the Collaborative Cross.

Salmonella infections typically cause self-limiting gastroenteritis, but in some individuals these bacteria can spread systemically and cause disseminated disease. Salmonella Typhimurium (STm), which causes severe systemic disease in most inbred mice, has been used as a model for disseminated disease. To screen for new infection phenotypes across a range of host genetics, we orally infected 32 Collaborative Cross (CC) mouse strains with STm and monitored their disease progression for seven days by telemetry. Our data revealed a broad range of phenotypes across CC strains in many parameters including survival, bacterial colonization, tissue damage, complete blood counts (CBC), and serum cytokines. Eighteen CC strains survived to day 7, while fourteen susceptible strains succumbed to infection before day 7. Several CC strains had sex differences in survival and colonization. Surviving strains had lower pre-infection baseline temperatures and were less active during their daily active period. Core body temperature disruptions were detected earlier after STm infection than activity disruptions, making temperature a better detector of illness. All CC strains had STm in spleen and liver, but susceptible strains were more highly colonized. Tissue damage was weakly negatively correlated to survival. We identified loci associated with survival on Chromosomes (Chr) 1, 2, 4, 7. Polymorphisms in Ncf2 and Slc11a1, known to reduce survival in mice after STm infections, are located in the Chr 1 interval, and the Chr 7 association overlaps with a previously identified QTL peak called Ses2. We identified two new genetic regions on Chr 2 and 4 associated with susceptibility to STm infection. Our data reveal the diversity of responses to STm infection across a range of host genetics and identified new candidate regions for survival of STm infection.

Risk perception and emotional wellbeing in healthcare workers involved in rapid response calls during the COVID-19 pandemic: A substudy of a cross-sectional survey.

BACKGROUND: Coronavirus disease-2019 (COVID-19) has effected major changes to healthcare delivery within acute care settings. Rapid response calls (RRCs) in healthcare organisations have been effective at identifying and urgently managing acute clinical deterioration. Code-95 RRC were introduced to prewarn healthcare workers (HCWs) attending to patients suspected or confirmed with COVID-19 infection. AIMS: The primary aim of the study was to identify the personal impact of the COVID-19 pandemic on HCWs involved in attending Code-95 RRC. We sought to evaluate their perception of risks and effects on wellbeing and identify potential opportunities for improvement at organisational levels. METHODS: We undertook a detailed survey on HCWs attending Code-95 RRCs, including questions that sought to understand the impact of the pandemic as well as their perception of infection risk and emotional wellbeing. This was a substudy of the prospective cross-sectional single-centre survey of HCWs that was conducted over a 3-week period at Frankston Hospital, Victoria, Australia. We adopted a quantitative content analysis approach for free-text responses in this secondary analysis. RESULTS: Four hundred two free-text comments were received from 297 respondents and were analysed. More than two-thirds (68%, 223/297) were female. Of all comments, 39% (155/402) were related to organisational issues including communication, confusion due to constantly changing infection control policies, and insufficient training. Thirty-three percent of comments (133/402) raised issues regarding the adequacy of personal protective equipment. Anxiety was reported in 25% of comments (101/402) with concerns predominantly relating to emotional stress and fatigue, risks of virus exposure and transmitting the infection to others, and COVID-19 precautions impairing care delivery. CONCLUSION(S): Our study raises important issues that have relevance for all healthcare organisations in the management of patients with COVID-19. These include the importance of improving communication, especially when infection control policies are revised, optimising training, maintaining adequate personal protective equipment, and HCW support. Early recognition and management of these issues are crucial to maintain optimal healthcare delivery.

'Code-95' rapid response calls for patients under airborne precautions in the COVID-19-era: a cross-sectional survey of healthcare worker perceptions.

BACKGROUND: To allow better allocation of staff and resources, rapid response teams attending to acutely deteriorating or aggressive patients with suspected or confirmed COVID-19 infection were pre-warned with the announcement of 'Code-95' with calls. AIM: To assess healthcare worker (HCW) perspectives on pre-warning rapid response calls (RRC) with 'Code-95' in announcements when attending to deteriorating or aggressive patients with suspected/confirmed COVID-19 infection. METHODS: Design: prospective cross-sectional single-centre survey of HCW over a 3-week period. SETTING: tertiary public hospital. PARTICIPANTS: HCW caring for deteriorating or aggressive patients. MAIN OUTCOME MEASURES: the primary outcome was to assess HCW perspectives in attending Code-95 calls. Secondary outcomes were to identify any differences related to craft group, age, experience or presence of comorbidities. RESULTS: A total of 297 responses was analysed; 86.7% of HCW (n = 257) attending Code-95 calls reported anxiety. Medical staff reported greater anxiety in comparison to nursing staff (93.8% vs 78.5%; P = 0.002). Efferent team reported higher anxiety in contrast to afferent team (92.6% vs 58.8%; P = 0.021). There was no significant difference in perceived anxiety based on age (≤40 vs >40 years of age), years of experience (≤5 vs >5 years), comorbidities or mental illness; 54% reported concerns about adequacy of infection-control policies and personal protective equipment; 45% were worried about inadequate training for responding to Code-95 calls. CONCLUSIONS: Most surveyed HCW supported Code-95 announcements pre-warning them of potential COVID-19 exposure when attending a RRC. However, the majority of HCW reported anxiety when attending these calls. Medical and efferent team HCW perceived greater anxiety compared to nursing and afferent team HCW. The Code-95 system to pre-warn rapid response teams may be a useful addition to protecting HCW from infectious diseases, although broader implementation will require greater resourcing, training and support.

Identifying links between monsoon variability and rice production in India through machine learning.

Climate change poses a major threat to global food security. Agricultural systems that rely on monsoon rainfall are especially vulnerable to changes in climate variability. This paper uses machine learning to deepen understanding of how monsoon variability impacts agricultural productivity. We demonstrate that random forest modelling is effective in representing rice production variability in response to monsoon weather variability. Our random forest modelling found monsoon weather predictors explain similar levels of detrended anomaly variation in both rice yield (33%) and area harvested (35%). The role of weather in explaining harvested rice area highlights that production area changes are an important pathway through which weather extremes impact agricultural productivity, which may exacerbate losses that occur through changes in per-area yields. We find that downwelling shortwave radiation flux is the most important weather variable in explaining variation in yield anomalies, with proportion of area under irrigation being the most important predictor overall. Machine learning modelling is capable of representing crop-climate variability in monsoonal agriculture and reveals additional information compared to traditional parametric models. For example, non-linear yield and area responses of irrigation, monsoon onset and season length all match biophysical expectations. Overall, we find that random forest modelling can reveal complex non-linearities and interactions between climate and rice production variability.

Importance of climatic and environmental change in the demography of a multi-brooded passerine, the woodlark Lullula arborea.

1. We examined the influence of local weather conditions on reproductive success, timing of breeding and survival in a population of a multi-brooded ground nesting passerine (woodlark Lullula arborea) over 35 years. 2. Woodlarks laid larger clutches when rainfall was low and temperature high during the egg-laying and pre-laying period. Nest success increased with higher temperatures during the nesting period. In successful nests, the number of chicks fledged per egg laid was greater when weather was drier during the brood stage. 3. Although woodlarks bred earlier in years with warmer early spring temperatures, with the onset of breeding varying by 25 days, there was no significant advance in the onset of breeding over the 35 years of study, due to considerable inter-annual variability, and no overall trend, in weather. 4. Simulation modelling of annual reproductive output demonstrated that earlier breeding could increase productivity by 23.5% in the warmest compared to the coldest year, due to birds having more nesting attempts. Other effects of weather on productivity affected breeding output to a lesser extent. 5. Effects of weather on productivity were minor compared to an increased rate of nest predation through the period of study, which reduced productivity by 49.8% by 2004 compared to 1971. 6. Turning points analysis identified three distinct demographic periods: from 1971 to 1988 the population grew slowly, during 1988-1999 the population grew rapidly, but after 1999 the population declined. Increased population growth after 1988 was associated with higher first-year survival rates (estimated using a population model). Population decline after 1999 was caused by a combination of reduced productivity (resulting from increased nest failure rates attributed to predation) and lower first-year survival rates, that appear unrelated to winter temperature. 7. Climate change (long-term changes in weather) did not explain the marked changes observed in the population trajectory over 35 years. We suggest that understanding effects of both climate and habitat change on populations is essential in predictive population modelling.

Seasonal dynamics in mosquito abundance and temperature do not influence avian malaria prevalence in the Himalayan foothills.

We examined seasonal prevalence in avian haemosporidians (Plasmodium and Haemoproteus) in migrant and resident birds in western Himalaya, India. We investigated how infection with haemosporidians in avian hosts is associated with temporal changes in temperature and mosquito abundance along with host abundance and life-history traits (body mass). Using molecular methods for parasite detection and sequencing partial cytochrome b gene, 12 Plasmodium and 27 Haemoproteus lineages were isolated. Our 1-year study from December 2008 to December 2009 in tropical Himalayan foothills revealed a lack of seasonal variation in Plasmodium spp. prevalence in birds despite a strong correlation between mosquito abundance and temperature. The probability of infection with Plasmodium decreased with increase in temperature. Total parasite prevalence and specifically Plasmodium prevalence showed an increase with average avian body mass. In addition, total prevalence exhibited a U-shaped relationship with avian host abundance. There was no difference in prevalence of Plasmodium spp. or Haemoproteus spp. across altitudes; parasite prevalence in high-altitude locations was mainly driven by the seasonal migrants. One Haemoproteus lineage showed cross-species infections between migrant and resident birds. This is the first molecular study in the tropical Himalayan bird community that emphasizes the importance of studying seasonal variation in parasite prevalence. Our study provides a basis for further evolutionary study on the epidemiology of avian malaria and spread of disease across Himalayan bird communities, which may not have been exposed to vectors and parasites throughout the year, with consequential implications to the risk of infection to naïve resident birds in high altitude.

Independent review of E2100: a phase III trial of bevacizumab plus paclitaxel versus paclitaxel in women with metastatic breast cancer.

PURPOSE: E2100, an open-label, randomized, phase III trial conducted by the Eastern Cooperative Oncology Group (ECOG), demonstrated a significant improvement in progression-free survival (PFS) and overall response rate (ORR) with paclitaxel plus bevacizumab compared with paclitaxel alone as initial chemotherapy for patients with HER2-negative metastatic breast cancer. METHODS: An independent, blinded review of radiologic and clinical data was performed, assessing progression and response according to Response Evaluation Criteria in Solid Tumors. In addition, ECOG's investigator assessments were reanalyzed using the same methods applied to the independent review. The primary end point was PFS as assessed by an independent review facility (IRF). RESULTS: The addition of bevacizumab to paclitaxel resulted in a statistically significant improvement in PFS using both the IRF and investigator assessments. Hazard ratios for PFS (0.48, 95% CI, 0.385 to 0.607; P < .0001 for the IRF v 0.42, 95% CI, 0.34 to 0.52; P < .0001 for ECOG investigators) and the improvement in median PFS (11.3 v 5.8 months for the IRF v 11.4 v 5.8 months for ECOG investigators) were similar. Among patients with measurable disease at baseline, the IRF-assessed ORR was significantly higher in patients treated with paclitaxel and bevacizumab (48.9% v 22.2%; P < .0001). CONCLUSION: The risk of progression was reduced by more than half and the ORR more than doubled with the addition of bevacizumab to weekly paclitaxel in both analyses, confirming a substantial and robust bevacizumab treatment effect. The consistency between the IRF and ECOG analyses validates the original data previously reported by ECOG in this open-label trial.