The impact of nitric oxide on HER family post-translational modification and downstream signaling in cancer.

The human epidermal growth factor receptor (HER) family consists of four members, activated by two families of ligands. They are known for mediating cell-cell interactions in organogenesis, and their deregulation has been associated with various cancers, including breast and esophageal cancers. In particular, aberrant epidermal growth factor receptor (EGFR) and HER2 signaling drive disease progression and result in poorer patient outcomes. Nitric oxide (NO) has been proposed as an alternative activator of the HER family and may play a role in this aberrant activation due to its ability to induce s-nitrosation and phosphorylation of the EGFR. This review discusses the potential impact of NO on HER family activation and downstream signaling, along with its role in the efficacy of therapeutics targeting the family.

Levels of Airborne Sound And Substrate-borne Vibration Calling Are Negatively Related Across Neotropical False-leaf Katydids.

Animals often signal in multiple sensory modalities to attract mates, but the level of signaling investment in each modality can differ dramatically between individuals and across species. When functionally overlapping signals are produced in different modalities, their relative use can be influenced by many factors, including differences in signal active space, energetic costs, and predation risk. Characterizing differences in total signal investment across time can shed light on these factors, but requires long focal recordings of signal production. Neotropical pseudophylline katydids produce mate advertisement signals as airborne sound and substrate-borne vibration. Airborne calls, produced via stridulation, are extremely short, high-frequency, and longer-range signals. Conversely, substrate-borne calls produced via abdominal tremulation are longer, low-frequency, relatively more energetically costly, and shorter-range signals. To examine patterns of stridulation and tremulation across species and test hypotheses about the drivers of signal use in each modality, we recorded multimodal signaling activity over 24 hours for males from ten pseudophylline species from a single Panamanian community. We also collected data on demographic and morphological species characteristics, and acoustic features of airborne calls, such as bandwidth, peak frequency, and duration. Finally, we generated a molecular phylogeny for these species and used phylogenetic generalized least squares models to test for relationships between variables while controlling for evolutionary relationships. We found a negative relationship between sound and vibration calling, indicating that substrate-borne vibrational signaling may compensate for reduced airborne signaling in these species. Sound call bandwidth and the proportion of males collected at lights, a proxy for the amount of male movement, also explained a significant amount of variation in sound calling across species, indicating that the overall relationship between the two types of calling signals may be mediated by the specific characteristics of the signals as well as other species traits.

Trends in observation stays for Medicare beneficiaries with and without Alzheimer's disease and related dementias.

BACKGROUND: There has been a marked rise in the use of observation care for Medicare beneficiaries visiting the emergency department (ED) in recent years. Whether trends in observation use differ for people with Alzheimer's disease and Alzheimer's disease-related dementias (AD/ADRD) is unknown. METHODS: Using a national 20% sample of Medicare beneficiaries ages 68+ from 2012 to 2018, we compared trends in ED visits and observation stays by AD/ADRD status for beneficiaries visiting the ED. We then examined the degree to which trends differed by nursing home (NH) residency status, assigning beneficiaries to four groups: AD/ADRD residing in NH (AD/ADRD+ NH+), AD/ADRD not residing in NH (AD/ADRD+ NH-), no AD/ADRD residing in NH (AD/ADRD- NH+), and no AD/ADRD not residing in NH (AD/ADRD- NH-). RESULTS: Of 7,489,780 unique beneficiaries, 18.6% had an AD/ADRD diagnosis. Beneficiaries with AD/ADRD had more than double the number of ED visits per 1000 in all years compared to those without AD/ADRD and saw a faster adjusted increase over time (+26.7 vs. +8.2 visits/year; p < 0.001 for interaction). The annual increase in the adjusted proportion of ED visits ending in observation was also greater among people with AD/ADRD (+0.78%/year, 95% CI 0.77-0.80%) compared to those without AD/ADRD (+0.63%/year, 95% CI 0.59-0.66%; p < 0.001 for interaction). Observation utilization was greatest for the AD/ADRD+ NH+ population and lowest for the AD/ADRD- NH- population, but the AD/ADRD+ NH- group saw the greatest increase in observation stays over time (+15.4 stays per 1000 people per year, 95% CI 15.0-15.7). CONCLUSIONS: Medicare beneficiaries with AD/ADRD have seen a disproportionate increase in observation utilization in recent years, driven by both an increase in ED visits and an increase in the proportion of ED visits ending in observation.

Clinical Outcomes Following Use of Tranexamic Acid in High Tibial Osteotomy: A Systematic Review.

This study aimed to evaluate the clinical outcomes following administration of tranexamic acid (TXA) in patients undergoing high tibial osteotomy (HTO) through a systematic review of current available evidence. A systematic database search of PubMed, Embase and Cumulative Index of Nursing and Allied Health Literature (CINAHL) was performed from inception up to December 2022, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). Inclusion criteria were (i) randomised control trials, cohort studies or case-control studies that had more than 10 patients; (ii) studies reporting outcomes after TXA administration, of any route, before or after HTO, compared to placebo, control and different doses or routes; and (iii) studies reporting blood loss, including haemoglobin (Hb) drop, estimated blood loss, transfusion requirement and complications. Case reports, reviews, abstracts, non-HTO studies, non-human studies and duplicates were excluded. A synthesized comparison of drain output, wound complications, transfusion requirement and pooled analyses of blood loss and Hb drop was performed. Eleven studies involving 974 patients were included. Nine studies had placebo comparison, and two used single-dose TXA versus multiple doses. All studies reported on postoperative hemoglobin and nine on blood loss. In the six TXA versus placebo studies reporting on total blood loss, the TXA group had a pooled, estimated standardised mean difference (SMD) in blood loss of -2.37 (95% confidence interval (CI) -3.67, -1.07; P = 0.0004). For the Hb drop, on postoperative days (PODs) one, two, and five, the SMDs were -0.97 (95% CI -1.19, -0.75; P < 0.00001) for POD1, -0.74 (95% CI -1.03, -0.46; P < 0.00001) for POD2 and -0.87 (95% CI -1.10, -0.64; P < 0.00001) for POD5. TXA administration in HTO significantly reduces perioperative blood loss. This can greatly improve recovery, reduce complications and shorten length of stay. This is especially pertinent given supply shortages of NHS blood resources.

Trends in healthy days at home for Medicare beneficiaries using the emergency department.

BACKGROUND: Older adults, particularly those with Alzheimer's Disease and Alzheimer's Disease Related Dementias (AD/ADRD), have high rates of emergency department (ED) visits and are at risk for poor outcomes. How best to measure quality of care for this population has been debated. Healthy Days at Home (HDAH) is a broad outcome measure reflecting mortality and time spent in facility-based healthcare settings versus home. We examined trends in 30-day HDAH for Medicare beneficiaries after visiting the ED and compared trends by AD/ADRD status. METHODS: We identified all ED visits among a national 20% sample of Medicare beneficiaries ages 68 and older from 2012 to 2018. For each visit, we calculated 30-day HDAH by subtracting mortality days and days spent in facility-based healthcare settings within 30 days of an ED visit. We calculated adjusted rates of HDAH using linear regression, accounting for hospital random effects, visit diagnosis, and patient characteristics. We compared rates of HDAH among beneficiaries with and without AD/ADRD, including accounting for nursing home (NH) residency status. RESULTS: We found fewer adjusted 30-day HDAH after ED visits among patients with AD/ADRD compared to those without AD/ADRD (21.6 vs. 23.0). This difference was driven by a greater number of mortality days, SNF days, and, to a lesser degree, hospital observation days, ED visits, and long-term hospital days. From 2012 to 2018, individuals living with AD/ADRD had fewer HDAH each year but a greater mean annual increase over time (p < 0.001 for the interaction between year and AD/ADRD status). Being a NH resident was associated with fewer adjusted 30-day HDAH for beneficiaries with and without AD/ADRD. CONCLUSIONS: Beneficiaries with AD/ADRD had fewer HDAH following an ED visit but saw moderately greater increases in HDAH over time compared to those without AD/ADRD. This trend was visit driven by declining mortality and utilization of inpatient and post-acute care.

Antibiotic-Prescribing Practices for Management of Childhood Diarrhea in 3 Sub-Saharan African Countries: Findings From the Vaccine Impact on Diarrhea in Africa (VIDA) Study, 2015-2018.

BACKGROUND: Despite antibiotic prescription being recommended for dysentery and suspected cholera only, diarrhea still triggers unwarranted antibiotic prescription. We evaluated antibiotic-prescribing practices and their predictors among children aged 2-59 months in the Vaccine Impact on Diarrhea in Africa (VIDA) Study performed in The Gambia, Mali, and Kenya. METHODS: VIDA was a prospective case-control study (May 2015-July 2018) among children presenting for care with moderate-to-severe diarrhea (MSD). We defined inappropriate antibiotic use as prescription or use of antibiotics when not indicated by World Health Organization (WHO) guidelines. We used logistic regression to assess factors associated with antibiotic prescription for MSD cases who had no indication for an antibiotic, at each site. RESULTS: VIDA enrolled 4840 cases. Among 1757 (36.3%) who had no apparent indication for antibiotic treatment, 1358 (77.3%) were prescribed antibiotics. In The Gambia, children who presented with a cough (adjusted odds ratio [aOR]: 2.05; 95% confidence interval [95% CI]: 1.21-3.48) were more likely to be prescribed an antibiotic. In Mali, those who presented with dry mouth (aOR: 3.16; 95% CI: 1.02-9.73) were more likely to be prescribed antibiotics. In Kenya, those who presented with a cough (aOR: 2.18; 95% CI: 1.01-4.70), decreased skin turgor (aOR: 2.06; 95% CI: 1.02-4.16), and were very thirsty (aOR: 4.15; 95% CI: 1.78-9.68) were more likely to be prescribed antibiotics. CONCLUSIONS: Antibiotic prescription was associated with signs and symptoms inconsistent with WHO guidelines, suggesting the need for antibiotic stewardship and clinician awareness of diarrhea case-management recommendations in these settings.

Prevalence of Salmonella in Stool During the Vaccine Impact on Diarrhea in Africa (VIDA) Study, 2015-2018.

BACKGROUND: Non-typhoidal Salmonella (NTS) is a common cause of gastroenteritis in young children, with limited data on NTS serovars and antimicrobial resistance in Africa. METHODS: We determined the prevalence of Salmonella spp. and frequency of antimicrobial resistance among serovars identified in stools of 0-59 month-old children with moderate-to-severe diarrhea (MSD) and controls enrolled in the Vaccine Impact on Diarrhea in Africa (VIDA) Study in The Gambia, Mali, and Kenya in 2015-2018, and compared with data from the Global Enteric Multicenter Study (GEMS; 2007-2010) and the GEMS-1A study (2011). Salmonella spp. was detected by quantitative real-time PCR (qPCR) and culture-based methods. Identification of serovars was determined by microbiological methods. RESULTS: By qPCR, the prevalence of Salmonella spp. among MSD cases was 4.0%, 1.6%, and 1.9% and among controls was 4.6%, 2.4%, and 1.6% in The Gambia, Mali, and Kenya, respectively, during VIDA. We observed year-to-year variation in serovar distribution and variation between sites. In Kenya, Salmonella enterica serovar Typhimurium decreased (78.1% to 23.1%; P < .001) among cases and controls from 2007 to 2018, whereas serogroup O:8 increased (8.7% to 38.5%; P = .04). In The Gambia, serogroup O:7 decreased from 2007 to 2018 (36.3% to 0%; P = .001) but S. enterica serovar Enteritidis increased during VIDA (2015 to 2018; 5.9% to 50%; P = .002). Only 4 Salmonella spp. were isolated in Mali during all 3 studies. Multidrug resistance was 33.9% in Kenya and 0.8% in The Gambia across all 3 studies. Ceftriaxone resistance was only observed in Kenya (2.3%); NTS isolates were susceptible to ciprofloxacin at all sites. CONCLUSIONS: Understanding variability in serovar distribution will be important for the future deployment of vaccines against salmonellosis in Africa.

Epidemiology of Enteroaggregative, Enteropathogenic, and Shiga Toxin-Producing Escherichia coli Among Children Aged <5 Years in 3 Countries in Africa, 2015-2018: Vaccine Impact on Diarrhea in Africa (VIDA) Study.

BACKGROUND: To address knowledge gaps regarding diarrheagenic Escherichia coli (DEC) in Africa, we assessed the clinical and epidemiological features of enteroaggregative E. coli (EAEC), enteropathogenic E. coli (EPEC), and Shiga toxin-producing E. coli (STEC) positive children with moderate-to-severe diarrhea (MSD) in Mali, The Gambia, and Kenya. METHODS: Between May 2015 and July 2018, children aged 0-59 months with medically attended MSD and matched controls without diarrhea were enrolled. Stools were tested conventionally using culture and multiplex polymerase chain reaction (PCR), and by quantitative PCR (qPCR). We assessed DEC detection by site, age, clinical characteristics, and enteric coinfection. RESULTS: Among 4840 children with MSD and 6213 matched controls enrolled, 4836 cases and 1 control per case were tested using qPCR. Of the DEC detected with TAC, 61.1% were EAEC, 25.3% atypical EPEC (aEPEC), 22.4% typical EPEC (tEPEC), and 7.2% STEC. Detection was higher in controls than in MSD cases for EAEC (63.9% vs 58.3%, P < .01), aEPEC (27.3% vs 23.3%, P < .01), and STEC (9.3% vs 5.1%, P < .01). EAEC and tEPEC were more frequent in children aged <23 months, aEPEC was similar across age strata, and STEC increased with age. No association between nutritional status at follow-up and DEC pathotypes was found. DEC coinfection with Shigella/enteroinvasive E. coli was more common among cases (P < .01). CONCLUSIONS: No significant association was detected between EAEC, tEPEC, aEPEC, or STEC and MSD using either conventional assay or TAC. Genomic analysis may provide a better definition of the virulence factors associated with diarrheal disease.

Survey-Based Assessment of Water, Sanitation, and Animal-Associated Risk Factors for Moderate-to-Severe Diarrhea in the Vaccine Impact on Diarrhea in Africa (VIDA) Study: The Gambia, Mali, and Kenya, 2015-2018.

BACKGROUND: Pediatric exposures to unsafe sources of water, unsafely managed sanitation, and animals are prevalent in low- and middle-income countries. In the Vaccine Impact on Diarrhea in Africa case-control study, we examined associations between these risk factors and moderate-to-severe diarrhea (MSD) in children <5 years old in The Gambia, Kenya, and Mali. METHODS: We enrolled children <5 years old seeking care for MSD at health centers; age-, sex-, and community-matched controls were enrolled at home. Conditional logistic regression models, adjusted for a priori confounders, were used to evaluate associations between MSD and survey-based assessments of water, sanitation, and animals living in the compound. RESULTS: From 2015 to 2018, 4840 cases and 6213 controls were enrolled. In pan-site analyses, children with drinking water sources below "safely managed" (onsite, continuously accessible sources of good water quality) had 1.5-2.0-fold higher odds of MSD (95% confidence intervals [CIs] ranging from 1.0 to 2.5), driven by rural site results (The Gambia and Kenya). In the urban site (Mali), children whose drinking water source was less available (several hours/day vs all the time) had higher odds of MSD (matched odds ratio [mOR]: 1.4, 95% CI: 1.1, 1.7). Associations between MSD and sanitation were site-specific. Goats were associated with slightly increased odds of MSD in pan-site analyses, whereas associations with cows and fowl varied by site. CONCLUSIONS: Poorer types and availability of drinking water sources were consistently associated with MSD, whereas the impacts of sanitation and household animals were context-specific. The association between MSD and access to safely managed drinking water sources post-rotavirus introduction calls for transformational changes in drinking water services to prevent acute child morbidity from MSD.

Norovirus Disease Among Children <5 Years in 3 Sub-Saharan African Countries: Findings From the Vaccine Impact on Diarrhea in Africa (VIDA) Study, 2015-2018.

BACKGROUND: To address a paucity of data from sub-Saharan Africa, we examined the prevalence, severity, and seasonality of norovirus genogroup II (NVII) among children <5 years old in The Gambia, Kenya, and Mali following rotavirus vaccine introduction. METHODS: Population-based surveillance was conducted to capture medically-attended moderate-to-severe diarrhea (MSD) cases, defined as a child 0-59 months old passing ≥3 loose stools in a 24-hour period with ≥1 of the following: sunken eyes, poor skin turgor, dysentery, intravenous rehydration, or hospitalization within 7 days of diarrhea onset. Diarrhea-free matched controls randomly selected from a censused population were enrolled at home. Stools from cases and controls were tested for enteropathogens, including norovirus and rotavirus, by TaqMan quantitative polymerase chain reaction (PCR) and conventional reverse transcription PCR. We used multiple logistic regression to derive adjusted attributable fractions (AFe) for each pathogen causing MSD, which takes into consideration the prevalence in both cases and controls, for each site and age. A pathogen was considered etiologic if AFe was ≥0.5. In further analyses focusing on the predominant NVII strains, we compared rotavirus and NVII severity using a 20-point modified Vesikari score and examined seasonal fluctuations. RESULTS: From May 2015 to July 2018, we enrolled 4840 MSD cases and 6213 controls. NVI was attributed to only 1 MSD episode. NVII was attributed to 185 (3.8%) of all MSD episodes and was the sole attributable pathogen in 139 (2.9%); peaking (36.0%) at age 6-8 months with majority (61.2%) aged 6-11 months. MSD cases whose episodes were attributed to NVII alone compared with rotavirus alone were younger (median age, 8 vs 12 months, P < .0001) and had less severe illness (median Vesikari severity score, 9 vs 11, P = .0003) but equally likely to be dehydrated. NVII occurred year-round at all study sites. CONCLUSIONS: Infants aged 6-11 months bear the greatest burden of norovirus disease, with NVII predominating. An early infant vaccine schedule and rigorous adherence to guidelines recommended for management of dehydrating diarrhea may offer substantial benefit in these African settings.

Exploring Survey-Based Water, Sanitation, and Animal Associations With Enteric Pathogen Carriage: Comparing Results in a Cohort of Cases With Moderate-to-Severe Diarrhea to Those in Controls in the Vaccine Impact on Diarrhea in Africa (VIDA) Study, 2015-2018.

BACKGROUND: The magnitude of pediatric enteric pathogen exposures in low-income settings necessitates substantive water and sanitation interventions, including animal feces management. We assessed associations between pediatric enteric pathogen detection and survey-based water, sanitation, and animal characteristics within the Vaccine Impact on Diarrhea in Africa case-control study. METHODS: In The Gambia, Kenya, and Mali, we assessed enteric pathogens in stool of children aged <5 years with moderate-to-severe diarrhea and their matched controls (diarrhea-free in prior 7 days) via the TaqMan Array Card and surveyed caregivers about household drinking water and sanitation conditions and animals living in the compound. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using modified Poisson regression models, stratified for cases and controls and adjusted for age, sex, site, and demographics. RESULTS: Bacterial (cases, 93%; controls, 72%), viral (63%, 56%), and protozoal (50%, 38%) pathogens were commonly detected (cycle threshold <35) in the 4840 cases and 6213 controls. In cases, unimproved sanitation (RR, 1.56; 95% CI, 1.12-2.17), as well as cows (RR, 1.61; 95% CI, 1.16-2.24) and sheep (RR, 1.48; 95% CI, 1.11-1.96) living in the compound, were associated with Shiga toxin-producing Escherichia coli. In controls, fowl (RR, 1.30; 95% CI, 1.15-1.47) were associated with Campylobacter spp. In controls, surface water sources were associated with Cryptosporidium spp., Shigella spp., heat-stable toxin-producing enterotoxigenic E. coli, and Giardia spp. CONCLUSIONS: Findings underscore the importance of enteric pathogen exposure risks from animals alongside more broadly recognized water and sanitation risk factors in children.

Shigella in Africa: New Insights From the Vaccine Impact on Diarrhea in Africa (VIDA) Study.

BACKGROUND: We evaluated the burden of Shigella spp from children aged 0-59 months with medically attended moderate-to-severe diarrhea and matched controls at sites in Mali, The Gambia, and Kenya participating in the Vaccine Impact on Diarrhea in Africa (VIDA) study from 2015 to 2018. METHODS: Shigella spp were identified using coprocultures and serotyping in addition to quantitative polymerase chain reaction (qPCR). Episode-specific attributable fractions (AFe) for Shigella were calculated using Shigella DNA quantity; cases with AFe ≥0.5 were considered to have shigellosis. RESULTS: The prevalence of Shigella was determined to be 359 of 4840 (7.4%) cases and 83 of 6213 (1.3%) controls by culture, and 1641 of 4836 (33.9%) cases and 1084 of 4846 (22.4%) controls by qPCR (cycle threshold <35); shigellosis was higher in The Gambia (30.8%) than in Mali (9.3%) and Kenya (18.7%). Bloody diarrhea attributed to Shigella was more common in 24- to 59-month-old children (50.1%) than 0- to 11-month-old infants (39.5%). The Shigella flexneri serogroup predominated among cases (67.6% of isolates), followed by Shigella sonnei (18.2%), Shigella boydii (11.8%), and Shigella dysenteriae (2.3%). The most frequent S. flexneri serotypes were 2a (40.6%), 1b (18.8%), 6 (17.5%), 3a (9.0%), and 4a (5.1%). Drug-specific resistance among 353 (98.3%) Shigella cases with AMR data was as follows: trimethoprim-sulfamethoxazole (94.9%), ampicillin (48.4%), nalidixic acid (1.7%), ceftriaxone (0.3%), azithromycin (0.3%), and ciprofloxacin (0.0%). CONCLUSIONS: A high prevalence of shigellosis continues in sub-Saharan Africa. Strains are highly resistant to commonly used antibiotics while remaining susceptible to ciprofloxacin, ceftriaxone, and azithromycin.

Listening to a popular upbeat song can lead to more adaptive cognitive inferences for stressful events in non-clinical adult populations.

OBJECTIVE: We tested the effect of music on idiographic cognitive inferences about stressful events. METHOD: In Study 1 (n = 336), adult participants from the United States were randomly assigned to non-familiar songs that differed by lyrical content and tempo. In Studies 2 (n = 302) and 3 (n = 323), adult participants from the United States were randomly assigned to either a positive, neutral or no-song condition. RESULTS: The results of Study 1 failed to support any of the study hypotheses. Given the null results, we decided to conduct a second study focused on increasing external validity and power (i.e., including fewer experimental conditions). The results of Study 2 showed that adults randomly assigned to a familiar upbeat song condition experienced an increase in positive affect and a decrease in event-specific negative cognitions. A third study was then conducted to replicate the results and rule out a potential confound. Results of Study 3 corroborated the results of Study 2. CONCLUSION: Taken together (Studies 2 and 3), results indicate it may be useful for future research to test the extent to which familiar upbeat music can be helpful during cognitive restructuring activities in psychotherapy to nudge people to generate more adaptive cognitions.

Association of Academic Medical Center Presence With Clinical Outcomes at Neighboring Community Hospitals Among Medicare Beneficiaries.

Importance: Studies suggest that academic medical centers (AMCs) have better outcomes than nonteaching hospitals. However, whether AMCs have spillover benefits for patients treated at neighboring community hospitals is unknown. Objective: To examine whether market-level AMC presence is associated with outcomes for patients treated at nonteaching hospitals within the same markets. Design, Setting, and Participants: This retrospective, population-based cohort study assessed traditional Medicare beneficiaries aged 65 years and older discharged from US acute care hospitals between 2015 and 2017 (100% sample). Data were analyzed from August 2021 to December 2022. Exposures: The primary exposure was market-level AMC presence. Health care markets (ie, hospital referral regions) were categorized by AMC presence (percentage of hospitalizations at AMCs) as follows: no presence (0%), low presence (>0% to 20%), moderate presence (>20% to 35%), and high presence (>35%). Main Outcomes and Measures: The primary outcomes were 30-day and 90-day mortality and healthy days at home (HDAH), a composite outcome reflecting mortality and time spent in facility-based health care settings. Results: There were 22 509 824 total hospitalizations, with 18 865 229 (83.8%) at non-AMCs. The median (IQR) age of patients was 78 (71-85) years, and 12 568 230 hospitalizations (55.8%) were among women. Of 306 hospital referral regions, 191 (62.4%) had no AMCs, 61 (19.9%) had 1 AMC, and 55 (17.6%) had 2 or more AMCs. Markets characteristics differed significantly by category of AMC presence, including mean population, median income, proportion of White residents, and physicians per population. Compared with markets with no AMC presence, receiving care at a non-AMC in a market with greater AMC presence was associated with lower 30-day mortality (9.5% vs 10.1%; absolute difference, -0.7%; 95% CI, -1.0% to -0.4%; P < .001) and 90-day mortality (16.1% vs 16.9%; absolute difference, -0.8%; 95% CI, -1.2% to -0.4%; P < .001) and more HDAH at 30 days (16.49 vs 16.12 HDAH; absolute difference, 0.38 HDAH; 95% CI, 0.11 to 0.64 HDAH; P = .005) and 90 days (61.08 vs 59.83 HDAH; absolute difference, 1.25 HDAH; 95% CI, 0.58 to 1.92 HDAH; P < .001), after adjustment. There was no association between market-level AMC presence and mortality for patients treated at AMCs themselves. Conclusions and Relevance: AMCs may have spillover effects on outcomes for patients treated at non-AMCs, suggesting that they have a broader impact than is traditionally recognized. These associations are greatest in markets with the highest AMC presence and persist to 90 days.

Getting the most out of maths: How to coordinate mathematical modelling research to support a pandemic, lessons learnt from three initiatives that were part of the COVID-19 response in the UK.

In March 2020 mathematics became a key part of the scientific advice to the UK government on the pandemic response to COVID-19. Mathematical and statistical modelling provided critical information on the spread of the virus and the potential impact of different interventions. The unprecedented scale of the challenge led the epidemiological modelling community in the UK to be pushed to its limits. At the same time, mathematical modellers across the country were keen to use their knowledge and skills to support the COVID-19 modelling effort. However, this sudden great interest in epidemiological modelling needed to be coordinated to provide much-needed support, and to limit the burden on epidemiological modellers already very stretched for time. In this paper we describe three initiatives set up in the UK in spring 2020 to coordinate the mathematical sciences research community in supporting mathematical modelling of COVID-19. Each initiative had different primary aims and worked to maximise synergies between the various projects. We reflect on the lessons learnt, highlighting the key roles of pre-existing research collaborations and focal centres of coordination in contributing to the success of these initiatives. We conclude with recommendations about important ways in which the scientific research community could be better prepared for future pandemics. This manuscript was submitted as part of a theme issue on "Modelling COVID-19 and Preparedness for Future Pandemics".

Mid-flight prey switching in the fringed-lipped bat (Trachops cirrhosus).

While foraging, eavesdropping predators home in on the signals of their prey. Many prey signal from aggregations, however, and predators already en route to attack one individual often encounter the signals of other prey. Few studies have examined whether eavesdropping predators update their foraging decisions by switching to target these more recently signaling prey. Switching could result in reduced localization errors and more current estimates of prey location. Conversely, assessing new cues while already in pursuit of another target might confuse or distract a predator. We tested whether fringed-lipped bats (Trachops cirrhosus) switch prey targets when presented with new cues mid-approach and examined how switching and the distance between simulated prey influence attack accuracy, latency, and prey capture success. During nearly 80% of attack flights, bats switched between túngara frog (Engystomops pustulosus) calls spaced 1 m apart, and switching resulted in lower localization errors. The switching rate was reduced, and the localization advantage disappeared for calls separated by 3 m. Regardless of whether bats switched targets, attacks were less accurate, took longer, and were less often successful when calls were spaced at larger distances, indicating a distraction effect. These results reveal that fringed-lipped bats attend to cues from non-targeted prey during attack flights and that the distance between prey alters the effectiveness of attacks, regardless of whether a bat switches targets. Understanding how eavesdropping predators integrate new signals from neighboring prey into their foraging decisions will lead to a fuller picture of the ways unintended receivers shape the evolution of signaling behavior.

Supporting and enabling health research in a local authority (SERLA): an exploratory study.

BACKGROUND: The use of research evidence to underpin public health practice and policy decisions in local government is strongly promoted but its implementation has not been straightforward. This study aimed to explore the factors, relationships and processes that contribute towards accessing, using, and generating research evidence that is relevant to local authority public health and social care and shapes its practice. METHODS: Semi-structured individual interviews with elected councillors, officers directly involved with public health and social care and with community members from one urban unitary authority in South England were conducted. Interviews were audio recorded, transcribed verbatim and thematically analysed. RESULTS: Fourteen participants took part in the semi-structured interviews. Local knowledge and evidence are prioritised, and anecdotal evidence is valued. The Director of Public Health was the principal source of information and support. Academics were rarely mentioned as information sources, and their involvement was ad hoc. The use of research evidence varied between individuals and departments, with wider engagement among public health specialists. Key barriers to the use of research evidence included access (not reported among public health professionals), research timeliness, local applicability, competence in finding and interpreting evidence and the role of research evidence within a political context. Public health and adult social care teams are not currently research active or research ready. Major barriers exist due to financial constraints and the socio-political context of local authorities. COVID-19 disrupted siloed ways of working, strengthening and opening potential collaborations within the local authority. This changed perspectives about the value of research but is likely time-limited unless underpinned by sustainable funding. CONCLUSION: Creating strategic level roles within local government to work with the Director of Public Health to champion the research agenda and embedding researchers within and across teams would build capacity for local authorities to sustainably co-create, undertake, and use evidence to better inform future actions.

Association Between the Functional Movement Screen and Landing Kinematics in Individuals With and Without Anterior Cruciate Ligament Reconstruction.

OBJECTIVES: The purpose of this study was to compare functional movement screen (FMS) scores and drop vertical jump (DVJ) kinematics between those with and without anterior cruciate ligament reconstruction (ACLR), and to evaluate the association between FMS composite score and DVJ kinematics. DESIGN: Cross-sectional. PARTICIPANTS: Sixty individuals with and without a history of ACLR. MAIN OUTCOME MEASURES: Composite FMS score and the dorsiflexion, knee-flexion, hip-flexion, knee abduction, hip adduction, and trunk-flexion angles during a DVJ. RESULTS: The FMS scores did not differ between groups (P > .05). There were smaller peak and initial contact hip-flexion angles in the ACLR and contralateral limbs compared with controls, and smaller peak dorsiflexion angles in the ACLR compared with contralateral limbs (P < .05). Lower FMS score was associated with a smaller peak dorsiflexion angle, smaller peak knee-flexion angle, and larger peak knee abduction angle in the ACLR limb (ΔR2 = .14-.23); a smaller peak dorsiflexion angle and smaller peak knee-flexion angle in the contralateral limb (ΔR2 = .17-.19); and a smaller peak dorsiflexion angle, smaller peak knee-flexion angle, and larger peak knee abduction angle in the control limb (ΔR2 = .16-.22). CONCLUSION: The FMS scores did not differ between groups, but were associated with DVJ kinematics and should be a complementary rather than substitute assessment.

Toward Mail-in-Sensors for SARS-CoV-2 Detection: Interfacing Gel Switch Resonators with Cell-Free Toehold Switches.

The COVID-19 pandemic has emphasized the importance of widespread testing to control the spread of infectious diseases. The rapid development, scale-up, and deployment of viral and antibody detection methods since the beginning of the pandemic have greatly increased testing capacity. Desirable attributes of detection methods are low product costs, self-administered protocols, and the ability to be mailed in sealed envelopes for the safe analysis and subsequent logging to public health databases. Herein, such a platform is demonstrated with a screen-printed, inductor-capacitor (LC) resonator as a transducer and a toehold switch coupled with cell-free expression as the biological selective recognition element. In the presence of the N-gene from SARS-CoV-2, the toehold switch relaxes, protease enzyme is expressed, and it degrades a gelatin switch that ultimately shifts the resonant frequency of the planar resonant sensor. The gelatin switch resonator (GSR) can be analyzed through a sealed envelope allowing for assessment without the need for careful sample handling with personal protective equipment or the need for workup with other reagents. The toehold switch used in this sensor demonstrated selectivity to SARS-CoV-2 virus over three seasonal coronaviruses and SARS-CoV-1, with a limit of detection of 100 copies/µL. The functionality of the platform and assessment in a sealed envelope with an automated scanner is shown with overnight shipment, and further improvements are discussed to increase signal stability and further simplify user protocols toward a mail-in platform.

Extramural venous invasion (EMVI) in colorectal cancer is associated with increased cancer recurrence and cancer-related death.

INTRODUCTION: Colorectal cancer (CRC) outcomes vary depending on tumour biology, with several features used to predict disease behaviour. Extramural venous invasion (EMVI) is associated with negative outcomes and its presence has been established as an indicator of more aggressive disease in CRC. METHODS: A prospectively maintained database was examined for patients undergoing curative resection for non-metastatic CRC between 2012 and 2018 in a tertiary institution. Clinicopathological factors were compared to assess their impact on recurrence, all-cause mortality and cancer-related death. Kaplan Meier analysis of the association between EMVI and these endpoints was performed, and univariable and multivariable analysis was carried out to establish the relationship of predictive factors in oncological outcomes. RESULTS: Eighty-eight (13.5%) of 654 patients developed recurrence. The mean time to recurrence was 19.8 ± 13.5 months. There were 36 (5.5%) cancer-related deaths at a mean duration of follow-up of 46.3 ± 21.6 months. Two hundred and sixty-six patients had extramural venous invasion (40.7%). EMVI was significantly associated with reduced overall recurrence-free survival, systemic recurrence-free survival, and increased cancer-related death on univariate analysis (p < 0.001 for all, Fig. 1), and multivariable analysis (OR 1.8 and 2.1 respectively, p < 0.05 for both). CONCLUSION: EMVI is associated with a poor prognosis, independent of stage, nodal status and other histopathological features. The presence of EMVI should be strongly considered as an indication for adjuvant therapy.