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African Americans (AAs) have higher prevalence of uncontrolled hypertension than Whites, which leads to reduced life expectancy. Barriers to achieving blood pressure control in AAs include mistrust of healthcare and poor adherence to medication and dietary recommendations. We conducted a pilot study of a church-based community health worker (CHW) intervention to reduce blood pressure among AAs by providing support and strategies to improve diet and medication adherence. To increase trust and cultural concordance, we hired and trained church members to serve as CHWs. AA adults (n = 79) with poorly controlled blood pressure were recruited from churches in a low-income, segregated neighborhood of Chicago. Participants had an average of 7.5 visits with CHWs over 6 months. Mean change in systolic blood pressure across participants was - 5 mm/Hg (p = 0.029). Change was greater among participants (n = 45) with higher baseline blood pressure (- 9.2, p = 0.009). Medication adherence increased at follow-up, largely due to improved timeliness of medication refills, but adherence to the DASH diet decreased slightly. Intervention fidelity was poor. Recordings of CHW visits revealed that CHWs did not adhere closely to the intervention protocol, especially with regard to assisting participants with action plans for behavior change. Participants gave the intervention high ratings for acceptability and appropriateness, and slightly lower ratings for feasibility of achieving intervention behavioral targets. Participants valued having the intervention delivered at their church and preferred a church-based intervention to an intervention conducted in a clinical setting. A church-based CHW intervention may be effective at reducing blood pressure in AAs.

Prostatic cysts are common in the adult male population with intervention of these cysts typically reserved for symptomatic patients. However, current literature is limited on the diagnosis and management of prostatic cysts in the pediatric population. We report the case of a 13-year-old boy with autosomal recessive polycystic kidney disease (ARPKD) who presented with an incidentally discovered prostatic cyst. This is the first known case report to highlight the clinical presentation, diagnosis, and management of an asymptomatic prostatic cyst in ARPKD.

Fragment-based drug discovery (FBDD) has emerged as a powerful strategy to confront the challenges faced by conventional drug development approaches, particularly in the context of central nervous system (CNS) disorders. FBDD involves the screening of libraries that comprise thousands of small molecular fragments, each no greater than 300 Da in size. Unlike the generally larger molecules from high-throughput screening that limit customisation, fragments offer a more strategic starting point. These fragments are inherently compact, providing a strong foundation with good binding affinity for the development of drug candidates. The minimal elaboration required to transition the hit into a drug-like molecule is not only accelerated, but also it allows for precise modifications to enhance both their activity and pharmacokinetic properties. This shift towards a fragment-centric approach has seen commercial success and holds considerable promise in the continued streamlining of the drug discovery and development process. In this review, we highlight how FBDD can be integrated into the CNS drug discovery process to enhance the exploration of a target. Furthermore, we provide recent examples where FBDD has been an integral component in CNS drug discovery programs, enabling the improvement of pharmacokinetic properties that have previously proven challenging. The FBDD optimisation process provides a systematic approach to explore this vast chemical space, facilitating the discovery and design of compounds piece by piece that are capable of modulating crucial CNS targets.

Objective:. To compare the rates of revision surgery for symptomatic neuromas in patients undergoing primary transtibial amputations with and without targeted muscle reinnervation (TMR). Design:. Retrospective cohort study. Setting:. Level I trauma hospital and tertiary military medical center. Patients/Participants:. Adult patients undergoing transtibial amputations with and without TMR. Intervention:. Transtibial amputation with targeted muscle reinnervation. Main Outcome Measurements:. Reoperation for symptomatic neuroma. Results:. During the study period, there were 112 primary transtibial amputations performed, 29 with TMR and 83 without TMR. Over the same period, there were 51 revision transtibial amputations performed, including 23 (21%) in the patients undergoing primary transtibial amputation at the study institution. The most common indications for revision surgery were wound breakdown/dehiscence (42%, n = 25), followed by symptomatic neuroma 18% (n = 9/51) and infection/osteomyelitis (17%, n = 10) as the most common indications. However, of the patients undergoing primary amputation at the study's institution, there was no difference in reoperation rates for neuroma when comparing the TMR group (3.6%, n = 1/28) and no TMR group (4.0%, n = 3/75) (P = 0.97). Conclusions:. Symptomatic neuroma is one of the most common reasons for revision amputation; however, this study was unable to demonstrate a difference in revision surgery rates for neuroma for patients undergoing primary transtibial amputation with or without targeted muscle reinnervation. Level of Evidence:. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Abstract Bacteria from the Turicibacter genus are prominent members of the mammalian gut microbiota and correlate with alterations in dietary fat and body weight, but the specific connections between these symbionts and host physiology are poorly understood. To address this knowledge gap, we characterize a diverse set of mouse- and human-derived Turicibacter isolates, and find they group into clades that differ in their transformations of specific bile acids. We identify Turicibacter bile salt hydrolases that confer strain-specific differences in bile deconjugation. Using male and female gnotobiotic mice, we find colonization with individual Turicibacter strains leads to changes in host bile acid profiles, generally aligning with those produced in vitro. Further, colonizing mice with another bacterium exogenously expressing bile-modifying genes from Turicibacter strains decreases serum cholesterol, triglycerides, and adipose tissue mass. This identifies genes that enable Turicibacter strains to modify host bile acids and lipid metabolism, and positions Turicibacter bacteria as modulators of host fat biology.

Abstract Background Limited information is available regarding the nutritive value and structural characteristics of multispecies swards when rotationally grazed. Methods Three farmlet types were investigated in terms of their nutritive value: Lolium perenne (LP); L. perenne+Trifolium repens (LP+TR); and a multispecies sward containing grasses, legumes and herbs (MSS). Farmlets were stocked with beef steers (2.5 livestock units ha−1), grazed on a 1 ha scale to 6 cm (MSS) and 4 cm (LP and LP+TR) residuals. Results A greater ash concentration was found in MSS than LP (84 vs. 75 g kg−1 DM). Both LP+TR and MSS had higher crude protein and lower neutral detergent fibre concentrations than LP. The relative ranking of water soluble carbohydrate and dry matter (DM) concentration was LP > LP+TR > MSS. Despite the leaf component of the LP farmlet contributing more to herbage DM, the organic matter digestibilities of the swards were similar. Conclusions The MSS and LP+TR farmlets achieved similar forage quality under intensive grazing to LP. However, it is worth noting that MSS had a higher concentration of acid detergent lignin, which can negatively impact digestibility. Further investigation is needed to determine optimal grazing management practices that can minimise the effects of higher lignin concentration on digestibility in multispecies swards.

Among 143 cases of National Healthcare Safety Network (NHSN) catheter-associated urinary tract infections (CAUTI), 40% were considered catheter-associated asymptomatic bacteriuria (CA-ASB), and 18% clinical CAUTI. An alternative source of fever was present in 70% of CA-ASB. NHSN CAUTI may not be an effective metric for tracking hospital-level infection prevention efforts.

We describe our experience implementing an intensive quality improvement cohort pilot focused on managing asymptomatic bacteriuria in 19 critical access hospitals. Participation in the pilot was high, and almost all sites identified an improvement goal and collected clinical data. Barriers to implementation included staffing shortages, turnover, and lack of bandwidth.

IntroductionAlthough studies have evaluated the hospital cost of care associated with treating patients with COVID-19, there are no studies that compare the hospital cost of care among racial and ethnic groups based on detailed cost accounting data. The aims of this study were to provide a detailed description of the hospital costs of COVID-19 based on individual resources during the hospital stay and standardized costs that do not rely on inflation adjustment and evaluate the extent to which hospital total cost of care for patients with COVID-19 differs by race and ethnicity.MethodsThis study used electronic medical record data from an urban academic medical center in Chicago, Illinois USA. Hospital cost of care was calculated using accounting data representing the cost of the resources used to the hospital (i.e., cost to the hospital, not payments). A multivariable generalized linear model with a log link function and inverse gaussian distribution family was used to calculate the average marginal effect (AME) for Black, White, and Hispanic patients. A second regression model further compared Hispanic patients by preferred language (English versus Spanish).ResultsIn our sample of 1,853 patients, the average adjusted cost of care was significantly lower for Black compared to White patients (AME = -$5,606; 95% confidence interval (CI), -$10,711 to -$501), and Hispanic patients had higher cost of care compared to White patients (AME = $8,539, 95% CI, $3,963 to $13,115). In addition, Hispanic patients who preferred Spanish had significantly higher cost than Hispanic patients who preferred English (AME = $11,866; 95% CI $5,302 to $18,431).ConclusionTotal cost of care takes into account both the intensity of the treatment as well as the duration of the hospital stay. Thus, policy makers and health systems can use cost of care as a proxy for severity, especially when looking at the disparities among different race and ethnicity groups.

Rationale & Objective: Noncitizen, undocumented patients with kidney failure have few treatment options in many states, although Illinois allows for patients to receive a transplant regardless of citizenship status. Little information exists about the experiences of noncitizen patients pursuing kidney transplantation. We sought to understand how access to kidney transplantation affects patients, their family, health care providers, and the health care system. Study Design: A qualitative study with virtually conducted semistructured interviews. Setting & Participants: Participants were transplant and immigration stakeholders (physicians, transplant center and community outreach professionals), and patients who have received assistance through the Illinois Transplant Fund (listed for or received transplant; patients could complete the interview with a family member). Analytical Approach: Interview transcripts were coded using open coding and were analyzed using thematic analysis methods with an inductive approach. Results: We interviewed 36 participants: 13 stakeholders (5 physicians, 4 community outreach stakeholders, and 4 transplant center professionals), 16 patients, and 7 partners. The following seven themes were identified: (1) devastation from kidney failure diagnosis, (2) resource needs for care, (3) communication barriers to care, (4) importance of culturally competent health care providers, (5) negative impacts of policy gaps, (6) new chance at life after transplant, and (7) recommendations for improving care. Limitations: The patients we interviewed were not representative of noncitizen patients with kidney failure overall or in other states. The stakeholders were also not representative of health care providers because they were generally well informed on kidney failure and immigration issues. Conclusions: Although patients in Illinois can access kidney transplants regardless of citizenship status, access barriers, and health care policy gaps continue to negatively affect patients, families, health care professionals, and the health care system. Necessary changes for promoting equitable care include comprehensive policies to increase access, diversifying the health care workforce, and improving communication with patients. These solutions would benefit patients with kidney failure regardless of citizenship.

Pig production in Ireland has gone through enormous changes during the past 60 yr, from pigs being primarily produced as a sideline on dairy farms, to an industry with one of the highest average herd sizes in Europe. This happened in part due to external pressure on the industry, whereby economies of scale were needed to compete with pigs produced in other countries, but largely due to the instigation of national programmes to support the pig industry through research, education and knowledge transfer. These efforts helped producers to take advantage of genetic improvements and monitor their own performance over time, as well as allowing for benchmarking of the national herd against other countries. The research programme initiated in the 1960s continues to grow and expand, providing the pig industry with internationally renowned data and knowledge in the areas of nutrition, animal welfare, the environment and energy use. Recent initiatives such as the establishment of the Teagasc and Irish Farmers Association Pig Joint Programme, and a Pig Health Check section in Animal Health Ireland, will help to promote further cross-collaboration between stakeholders in the pig industry, and enable it to rise to the challenges of the years ahead.

To characterize sea turtle bycatch in fixed-gear fisheries in Massachusetts, USA, we analyzed a 15 yr dataset of entanglement reports and detailed documentation from disentanglement operations. Almost all (272) of the 280 confirmed entanglements involved leatherback turtles Dermochelys coriacea. The majority of turtles were entangled in actively fished (96%), commercial (94%) pot/trap gear with unbroken/untriggered weak links, specifically the buoy lines marking lobster, whelk, and fish traps. Most reports came from recreational boaters (62%) and other sources (26%), rather than commercial fishers (12%). Leatherback entanglements occurred from May to November, with peak reporting in August, and included adult males, adult females, and subadults. All entanglements involved the turtle’s neck and/or front flippers, with varying degrees of visible injuries; 47 entangled leatherbacks were dead in gear, 224 were alive at first sighting, and 1 case was unknown. Post-release monitoring suggested turtles can survive for days to years after disentanglement, but data were limited. While the observed entanglements in our study are low relative to global bycatch, these numbers should be considered a minimum. Our findings are comparable to observed numbers of leatherbacks taken in Canadian fixed-gear fisheries, and represent just one of multiple, cumulative threats in the North Atlantic. Managers should focus on strategies to reduce the co-occurrence of sea turtles and fixed-fishing gear, including reductions in the number of buoy lines allowed (e.g. replace single sets with trawls), seasonal and area closures targeted to reduce sea turtle-gear interaction, and encourage the development of emerging technologies such as ‘ropeless’ fishing.

The ability to provide feedback to a colleague is a key skill required for professional growth and patient safety. However, these conversations are limited by time constraints, differences in values, and a culture of “noninterference.” This advocacy-inquiry-identify-teach framework creates an organized approach to initiating successful “challenging” conversations with peers.

Background. Recently, the National Council on Disability urged the Commission on Dental Accreditation to require more thorough training in the care of developmentally disabled patients. Curricula is early in its development and its’ effectiveness is unknown. Objectives. The aim of this study was to determine if special needs dental education has had an impact on providers’ professional behavior, practice characteristics, attitudes, and confidence when treating these patients and managing their dental anxiety. Methods. A nonrandomized, noninterventional, and anonymous, Qualtrics survey was administered prospectively to members of one local and one national organization. Results. Of the 107 respondents (response rate of 81.06%), 89% treat special needs patients. Positive reinforcement (88.64%), distraction (85.23%), and enhancing control (85.23%) were the modalities most used by these participants. Regarding treating this population, the average response regarding both confidence and wanting to learn more fell between disagree and agree at 2.92, while the average response regarding concern about safety fell between agree and strongly agree at 3.22. Level of specific expertize had the strongest influence on a provider’s decision to treat, while reimbursement level had the least influence. Among participants who completed postdoctoral education, the average response for how well their education prepared them to manage patients with special needs was higher for their postdoctoral training compared to their dental school training, with pediatric dentists reporting the highest rate of preparation. No correlation was found between year of dental school graduation and how well they felt their education prepared them for treating this population. Significance level was set at 5%. Conclusion. Dental education can have a significant impact on dentists’ knowledge, attitudes, beliefs, and confidence about treating those with developmental disabilities and managing their dental anxiety. Acknowledging that this relationship exists should encourage educational improvements in this area.

Bacterial superinfection and antibiotic prescribing in the setting of the current mpox outbreak are not well described in the literature. This retrospective observational study revealed low prevalence (11%) of outpatient antibiotic prescribing for bacterial superinfection of mpox lesions; at least 3 prescriptions (23%) were unnecessary.

Abstract. Background:. The purpose of this study is to investigate the most common reasons for and judicial outcomes of malpractice claims related to stress urinary incontinence (SUI) management. Materials and methods:. Using the Westlaw database, a search was performed using the terms “medical malpractice” or “negligence” in combination with “stress incontinence” or “stress urinary incontinence” between January 1, 1990 and January 1, 2020. Extracted information included trial date, demographic information, defendant profession, procedure performed, procedure complications, alleged malpractice, trial outcome, and monetary award. Data were analyzed using descriptive statistics. Results:. The Westlaw search yielded 79 case results. Of the cases, 70.4% (n = 38/54) had a defense verdict, 22.2% (n = 12/54) had a plaintiff verdict, and 7.4% (n = 4/54) were settled. The most commonly implicated procedure was mid-urethral sling (63.2%, n = 36/57). Among the plaintiffs, 48.4% (n = 61/126) claimed negligence in preoperative care, 33.3% (n = 42/126) claimed negligence in surgical performance, and 18.3% (n = 23/126) claimed negligence in postoperative care. Lack of informed consent was the most common complaint related to negligence in preoperative care (42.6%, n = 26/61). The average indemnity payment was $1,253,644 for preoperative care negligence, $1,254,491 for surgical performance negligence, and $2,239,198 for postoperative care negligence. Of the defendants, 63.4% (n = 52) were gynecologists and 36.6% (n = 30) were urologists. Conclusions:. Negligent preoperative care, with a particular emphasis on failure to obtain informed consent, and negligent surgical performance are the leading causes of malpractice claims during SUI management. Mid-urethral sling was the most commonly litigated procedure. This study highlights key factors to consider in minimizing malpractice risk during SUI management.

Abstract Transition metal chalcogenide nanoparticles (NPs) are of interest for energy applications, including batteries, supercapacitors, and electrocatalysis. Many methods have been established for synthesizing Ni NPs, and conversion chemistry to form Ni oxide and phosphides from template Ni NPs is well‐understood. Sulfidation and selenidation of Ni NPs have been much less explored, however. We report a method for the conversion of Ni template NPs into sulfide and selenide product NPs using elemental sulfur, 1‐hexadecanthiol, thiourea, trioctylphosphine sulfide, elemental selenium, and selenourea. While maintaining mole ratios of 2 mmol sulfur/selenium precursor: mmol Ni, products with phases of Ni3S2, Ni9S8, NiS, NiSO4·6H2O, Ni3S4, Ni3Se2, and NiSe have been obtained. The products have voids that form through the Kirkendall effect during interdiffusion. Trends relating the chemical properties of the precursors to the phases of the products have been identified. While some precursors contained phosphorus, there was no significant incorporation of phosphorus in any of the products. An increase of the NP size during sulfidation and selenidation is consistent with ripening. The application of Ni sulfide and selenide NPs as electrocatalysts for the hydrogen evolution reaction is also demonstrated.

A uniparental disomy (UPD) screen using whole genome sequencing (WGS) data from 164 trios with rare disorders in the Irish population was performed to identify large runs of homozygosity of uniparental origin that may harbour deleterious recessive variants. Three instances of whole chromosome uniparental isodisomy (UPiD) were identified: one case of maternal isodisomy of chromosome 1 and two cases of paternal isodisomy of chromosome 2. We identified deleterious homozygous variants on isodisomic chromosomes in two probands: a novel p (Glu59ValfsTer20) variant in TMCO1, and a p (Pro222Leu) variant in PRKRA, respectively. The overall prevalence of whole chromosome UPiD in our cohort was 1 in 55 births, compared to 1 in ∼7,500 births in the general population, suggesting a higher frequency of UPiD in rare disease cohorts. As a distinct mechanism underlying homozygosity compared to biallelic inheritance, the identification of UPiD has important implications for family planning and cascade testing. Our study demonstrates that UPD screening may improve diagnostic yields by prioritising UPiD chromosomes during WGS analysis.

Introduction: Influenza vaccines are commonly provided through community health events and primary care appointments. However, acute unscheduled healthcare visits such as emergency department (ED) visits are increasingly viewed as important vaccination opportunities. Emergency departments may be well-positioned to complement broader public health efforts with integrated vaccination programs. Methods: We studied an ED-based influenza vaccination initiative in an urban hospital and examined patient-level factors associated with screening and vaccination uptake. Our analyses included patient visits to the ED from October 1, 2019–April 1, 2020. Results: The influenza screening and vaccination program proved feasible. Of the 20,878 ED visits that occurred within the study period, 3,565 (17.1%) included a screening for influenza vaccine eligibility; a small proportion (11.5%) of the patients seen had multiple screenings. Among the patients screened eligible for the vaccine, 916 ultimately received an influenza vaccination while in the ED (43.7% of eligible patients). There was significant variability in the characteristics of patients who were and were not screened and vaccinated. Age, gender, race, preferred language, and receipt of a flu vaccine in prior years were associated with screening and/or receiving a vaccine in the ED. Conclusion: Vaccination programs in the ED can boost community vaccination rates and play a role in both preventing and treating current and future vaccine-preventable public health crises, although efforts must be made to deliver services equitably.

Abstract Background A new variance estimator is derived and tested for big BAF (Basal Area Factor) sampling which is a forest inventory system that utilizes Bitterlich sampling (point sampling) with two BAF sizes, a small BAF for tree counts and a larger BAF on which tree measurements are made usually including DBHs and heights needed for volume estimation. Methods The new estimator is derived using the Delta method from an existing formulation of the big BAF estimator as consisting of three sample means. The new formula is compared to existing big BAF estimators including a popular estimator based on Bruce’s formula. Results Several computer simulation studies were conducted comparing the new variance estimator to all known variance estimators for big BAF currently in the forest inventory literature. In simulations the new estimator performed well and comparably to existing variance formulas. Conclusions A possible advantage of the new estimator is that it does not require the assumption of negligible correlation between basal area counts on the small BAF factor and volume-basal area ratios based on the large BAF factor selection trees, an assumption required by all previous big BAF variance estimation formulas. Although this correlation was negligible on the simulation stands used in this study, it is conceivable that the correlation could be significant in some forest types, such as those in which the DBH-height relationship can be affected substantially by density perhaps through competition. We derived a formula that can be used to estimate the covariance between estimates of mean basal area and the ratio of estimates of mean volume and mean basal area. We also mathematically derived expressions for bias in the big BAF estimator that can be used to show the bias approaches zero in large samples on the order of 1 n $\frac {1}{n}$ where n is the number of sample points.

Abstract Reduced gravity, or microgravity, can have a pronounced impact on the physiology of animals, but the effects on their associated microbiomes are not well understood. Here, the impact of modeled microgravity on the shedding of Gram-negative lipopolysaccharides (LPS) by the symbiotic bacterium Vibrio fischeri was examined using high-aspect ratio vessels. LPS from V. fischeri is known to induce developmental apoptosis within its symbiotic tissues, which is accelerated under modeled microgravity conditions. In this study, we provide evidence that exposure to modeled microgravity increases the amount of LPS released by the bacterial symbiont in vitro. The higher rates of shedding under modeled microgravity conditions are associated with increased production of outer-membrane vesicles (OMV), which has been previously correlated to flagellar motility. Mutants of V. fischeri defective in the production and rotation of their flagella show significant decreases in LPS shedding in all treatments, but levels of LPS are higher under modeled microgravity despite loss of motility. Modeled microgravity also appears to affect the outer-membrane integrity of V. fischeri, as cells incubated under modeled microgravity conditions are more susceptible to cell-membrane-disrupting agents. These results suggest that, like their animal hosts, the physiology of symbiotic microbes can be altered under microgravity-like conditions, which may have important implications for host health during spaceflight.

Abstract Background The double sampling method known as “big BAF sampling” has been advocated as a way to reduce sampling effort while still maintaining a reasonably precise estimate of volume. A well-known method for variance determination, Bruce’s method, is customarily used because the volume estimator takes the form of a product of random variables. However, the genesis of Bruce’s method is not known to most foresters who use the method in practice. Methods We establish that the Taylor series approximation known as the Delta method provides a plausible explanation for the origins of Bruce’s method. Simulations were conducted on two different tree populations to ascertain the similarities of the Delta method to the exact variance of a product. Additionally, two alternative estimators for the variance of individual tree volume-basal area ratios, which are part of the estimation process, were compared within the overall variance estimation procedure. Results The simulation results demonstrate that Bruce’s method provides a robust method for estimating the variance of inventories conducted with the big BAF method. The simulations also demonstrate that the variance of the mean volume-basal area ratios can be computed using either the usual sample variance of the mean or the ratio variance estimators with equal accuracy, which had not been shown previously for Big BAF sampling. Conclusions A plausible explanation for the origins of Bruce’s method has been set forth both historically and mathematically in the Delta Method. In most settings, there is evidently no practical difference between applying the exact variance of a product or the Delta method—either can be used. A caution is articulated concerning the aggregation of tree-wise attributes into point-wise summaries in order to test the correlation between the two as a possible indicator of the need for further covariance augmentation.

Abstract Background ALK-rearrangement is observed in

Abstract Background The evaluation of circulating tumour DNA (ctDNA) from clinical blood samples, liquid biopsy, offers several diagnostic advantages compared with traditional tissue biopsy, such as shorter processing time, reduced patient risk and the opportunity to assess tumour heterogeneity. The historically poor sensitivity of ctDNA testing, has restricted its integration into routine clinical practice for non-metastatic disease. The early kinetics of ctDNA during radical radiotherapy for localised NSCLC have not been described with ultra-deep next generation sequencing previously. Materials and methods Patients with CT/PET-staged locally advanced, NSCLC prospectively consented to undergo serial venepuncture during the first week of radical radiotherapy alone. All patients received 55Gy in 20 fractions. Plasma samples were processed using the commercially available Roche AVENIO Expanded kit (Roche Sequencing Solutions, Pleasanton, CA, US) which targets 77 genes. Results Tumour-specific mutations were found in all patients (1 in 3 patients; 2 in 1 patient, and 3 in 1 patient). The variant allele frequency of these mutations ranged from 0.05–3.35%. In 2 patients there was a transient increase in ctDNA levels at the 72 h timepoint compared to baseline. In all patients there was a non-significant decrease in ctDNA levels at the 7-day timepoint in comparison to baseline (p = 0.4627). Conclusion This study demonstrates the feasibility of applying ctDNA-optimised NGS protocols through specified time-points in a small homogenous cohort of patients with localised lung cancer treated with radiotherapy. Studies are required to assess ctDNA kinetics as a predictive biomarker in radiotherapy. Priming tumours for liquid biopsy using radiation warrants further exploration.

The objectives of this study were to evaluate the effects of (1) protein supplementation strategy, (2) cow genotype and (3) an interaction between protein supplementation strategy and cow genotype on milk production and nitrogen (N) utilisation efficiency (milk N output/ total dietary N intake × 100; NUE) in late-lactation, spring-calving grazing dairy cows. A 2 × 2 factorial arrangement experiment, with two feeding strategies [13% (lower crude protein; LCP) and 18% CP (higher CP; HCP) supplements with equal metabolisable protein supply] offered at 3.6 kg dry matter/cow perday, and two cow genotype groups [lower milk genotype (LM) and higher milk genotype (HM)], was conducted over 53 days. Cows were offered 15 kg dry matter of grazed herbage/cow/day. Herbage intake was controlled using electric strip wires which allowed cows to graze their daily allocation-only. There was an interaction for herbage dry matter intake within cows offered HCP, where higher milk genotype (HM) cows had increased herbage dry matter intake (+0.58 kg) compared to lower milk genotype (LM) cows. Offering cows LCP decreased fat + protein yield (−110 g) compared to offering cows HCP. Offering cows LCP decreased the total feed N proportion that was recovered in the urine (−0.007 proportion units) and increased the total feed N proportion that was recovered in the faeces (+0.008 proportion units) compared to offering cows HCP. In conclusion, our study shows that reducing the supplementary CP concentration from 18% to 13% resulted in decreased milk production (−9.8%), reduced partitioning of total feed N to urine (−0.9%) and increased partitioning of total feed N to faeces (+14%) in late lactation, grazing dairy cows.

We compared experiences with The Multifaceted Intervention to Improve Prescribing for Acute Respiratory Infection for Adult and Children in Emergency Department and Urgent Care Settings versus Choosing Wisely to evaluate inappropriate antimicrobial prescribing in ambulatory care. Both identified the same clinics, diagnoses, and antibiotics for high-yield antibiotic stewardship interventions.

IMPORTANCE:. Studying interhospital transfer of critically ill patients with coronavirus disease 2019 pneumonia in the spring 2020 surge may help inform future pandemic management. OBJECTIVES:. To compare outcomes for mechanically ventilated patients with coronavirus disease 2019 transferred to a tertiary referral center with increased surge capacity with patients admitted from the emergency department. DESIGN, SETTING, PARTICIPANTS:. Observational cohort study of single center urban academic medical center ICUs. All patients admitted and discharged with coronavirus disease 2019 pneumonia who received invasive ventilation between March 17, 2020, and October 14, 2020. MAIN OUTCOME AND MEASURES:. Demographic and clinical variables were obtained from the electronic medical record. Patients were classified as emergency department admits or interhospital transfers. Regression models tested the association between transfer status and survival, adjusting for demographics and presentation severity. RESULTS:. In total, 298 patients with coronavirus disease 2019 pneumonia were admitted to the ICU and received mechanical ventilation. Of these, 117 were transferred from another facility and 181 were admitted through the emergency department. Patients were primarily male (64%) and Black (38%) or Hispanic (45%). Transfer patients differed from emergency department admits in having English as a preferred language (71% vs 56%; p = 0.008) and younger age (median 57 vs 61 yr; p < 0.001). There were no differences in race/ethnicity or primary payor. Transfers were more likely to receive extracorporeal membrane oxygenation (12% vs 3%; p = 0.004). Overall, 50 (43%) transferred patients and 78 (43%) emergency department admits died prior to discharge. There was no significant difference in hospital mortality or days from intubation to discharge between the two groups. CONCLUSIONS AND RELEVANCE:. In a single-center retrospective cohort, no significant differences in hospital mortality or length of stay between interhospital transfers and emergency department admits were found. While more study is needed, this suggests that interhospital transfer of critically ill patients with coronavirus disease 2019 can be done safely and effectively.

Abstract Background The Chapman-Richards distribution is developed as a special case of the equilibrium solution to the McKendrick-Von Foerster equation. The Chapman-Richards distribution incorporates the vital rate assumptions of the Chapman-Richards growth function, constant mortality and recruitment into the mathematical form of the distribution. Therefore, unlike ‘assumed’ distribution models, it is intrinsically linked with the underlying vital rates for the forest area under consideration. Methods It is shown that the Chapman-Richards distribution can be recast as a subset of the generalized beta distribution of the first kind, a rich family of assumed probability distribution models with known properties. These known properties for the generalized beta are then immediately available for the Chapman-Richards distribution, such as the form of the compatible basal area-size distribution. A simple two-stage procedure is proposed for the estimation of the model parameters and simulation experiments are conducted to validate the procedure for four different possible distribution shapes. Results The simulations explore the efficacy of the two-stage estimation procedure; these cover the estimation of the growth equation and mortality—recruitment derives from the equilibrium assumption. The parameter estimates are shown to depend on both the sample size and the amount of noise imparted to the synthetic measurements. The results vary somewhat by distribution shape, with the smaller, noisier samples providing less reliable estimates of the vital rates and final distribution forms. Conclusions The Chapman-Richards distribution in its original form, or recast as a generalized beta form, presents a potentially useful model integrating vital rates and stand diameters into a flexible family of resultant distributions shapes. The data requirements are modest, and parameter estimation is straightforward provided the minimal recommended sample sizes are obtained.

Abstract Background There are complex interactions between aging, frailty, diet, and the gut microbiota; modulation of the gut microbiota by diet could lead to healthier aging. The purpose of this study was to test the effect of diets differing in sugar, fat, and fiber content upon the gut microbiota of mice humanized with microbiota from healthy or frail older people. We also performed a 6-month dietary fiber supplementation in three human cohorts representing three distinct life-stages. Methods Mice were colonized with human microbiota and then underwent an 8-week dietary intervention with either a high-fiber/low-fat diet typical of elderly community dwellers or a low-fiber/high-fat diet typical of long-stay residential care subjects. A cross-over design was used where the diets were switched after 4 weeks to the other diet type to identify responsive taxa and innate immunity changes. In the human intervention, the subjects supplemented their normal diet with a mix of five prebiotics (wheat dextrin, resistant starch, polydextrose, soluble corn fiber, and galactooligo-saccharide) at 10 g/day combined total, for healthy subjects and 20 g/day for frail subjects, or placebo (10 g/day maltodextrin) for 26 weeks. The gut microbiota was profiled and immune responses were assayed by T cell markers in mice, and serum cytokines in humans. Results Humanized mice maintained gut microbiota types reflecting the respective healthy or frail human donor. Changes in abundance of specific taxa occurred with the diet switch. In mice with the community type microbiota, the observed differences reflected compositions previously associated with higher frailty. The dominance of Prevotella present initially in community inoculated mice was replaced by Bacteroides, Alistipes, and Oscillibacter. Frail type microbiota showed a differential effect on innate immune markers in both conventional and germ-free mice, but a moderate number of taxonomic changes occurring upon diet switch with an increase in abundance of Parabacteroides, Blautia, Clostridium cluster IV, and Phascolarctobacterium. In the human intervention, prebiotic supplementation did not drive any global changes in alpha- or beta-diversity, but the abundance of certain bacterial taxa, particularly Ruminococcaceae (Clostridium cluster IV), Parabacteroides, Phascolarctobacterium, increased, and levels of the chemokine CXCL11 were significantly lower in the frail elderly group, but increased during the wash-out period. Conclusions Switching to a nutritionally poorer diet has a profound effect on the microbiota in mouse models, with changes in the gut microbiota from healthy donors reflecting previously observed differences between elderly frail and non-frail individuals. However, the frailty-associated gut microbiota did not reciprocally switch to a younger healthy-subject like state, and supplementation with prebiotics was associated with fewer detected effects in humans than diet adjustment in animal models.

Purpose: To evaluate current practice patterns in anterior cruciate ligament reconstruction (ACLR) surgery among fellowship-trained military surgeons. Methods: The MOTION database is a prospectively collected dataset of intraoperative variables across the Military Health System. This database was queried using Current Procedural Terminology code 29888 for ACLR among active-duty service members between October 2016 and December 2019. The intraoperative data pertaining to ACLR involving both isolated primary ACLRs and primary ACLRs combined with meniscal or chondral injuries were extracted with patient age, sex, and rank. Results: Two hundred sixty-six primary ACLRs performed by 21 fellowship-trained orthopaedic surgeons at 9 MTFs were identified. The mean age of patients undergoing ACLR was 27.2 ± 7.7 years. Bone–patellar tendon–bone autograft was the most commonly used graft source (137 of 266 [51.5%] cases.) Meniscal injuries were treated with an isolated debridement in 53 of 156 (34.0%) tears, whereas meniscal repair was performed in 86 of 156 (55.1%) tears. Concomitant chondral pathology was noted in 43 of 266 cases (16.2%) and most commonly addressed with chondroplasty (25 of 49 [51.0%] chondral lesions). Conclusions: Bone–patellar tendon–bone autograft was the most commonly used graft type in ACLR among fellowship-trained surgeons treating active-duty service members. Concomitant meniscal pathology was encountered at rates comparable with what has been previously reported, and meniscal repair was favored over meniscal debridement in more than 50% cases. Level of Evidence: Level IV: Therapeutic case series.

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Emissions of methane (CH4) from dairy production systems are environmentally detrimental and represent an energy cost to the cow. This study evaluated the effect of varying C18 fatty acid sources on CH4 emissions, milk production and rumen methanogen populations in grazing lactating dairy cows. Forty-five Holstein Friesian cows were randomly allocated to one of three treatments (n = 15). Cows were offered 15 kg dry matter (DM)/d of grazed pasture plus supplementary concentrates (4 kg DM/d) containing either stearic acid (SA), linseed oil (LO), or soy oil (SO). Cows offered LO and SO had lower pasture DM intake (DMI) than those offered SA (11.3, 11.5 vs. 12.6 kg/d). Cows offered LO and SO had higher milk yield (21.0, 21.3 vs. 19.7 kg/d) and milk protein yield (0.74, 0.73 vs. 0.67 kg/d) than those offered SA. Emissions of CH4 (245 vs. 293, 289 g/d, 12.4 vs. 15.7, 14.8 g/kg of milk and 165 vs. 207, 195 g/kg of milk solids) were lower for cows offered LO than those offered SA or SO. Methanobrevibacter ruminantium abundance was reduced in cows offered LO compared to SA. Offering supplementary concentrates containing LO can reduce enteric CH4 emissions from pasture fed dairy cows.

To address the lack of a truly portable, universal reference mapping population for perennial ryegrass, we have been developing a recombinant inbred line (RIL) mapping population of perennial ryegrass derived via single seed descent from a well-characterized F2 mapping population based on genetically distinct inbred parents in which the natural self-incompatibility (SI) system of perennial ryegrass has been overcome. We examined whether it is possible to create a genotyping by sequencing (GBS) based genetic linkage map in a small population of the F6 generation of this population. We used 41 F6 genotypes for GBS with PstI/MspI-based libraries. We successfully developed a genetic linkage map comprising 6074 SNP markers, placing a further 22080 presence and absence variation (PAV) markers on the map. We examined the resulting genetic map for general and RIL specific features. Overall segregation distortion levels were similar to those experienced in the F2 generation, but segregation distortion was reduced on linkage group 6 and increased on linkage group 7. Residual heterozygosity in the F6 generation was observed at a level of 5.4%. There was a high proportion of chromosomes (30%) exhibiting the intact haplotype of the original inbred parents of the F1 genotype from which the population is derived, pointing to a tendency for chromosomes to assort without recombining. This could affect the applicability of these lines and might make them more suitable for situations where repressed recombination is an advantage. Inter- and intra-chromosomal linkage disequilibrium (LD) analysis suggested that the map order was robust. We conclude that this RIL population, and subsequent F7 and F8 generations will be useful for genetic analysis and phenotyping of agronomic and biological important traits in perennial ryegrass.

The aim of this study is to assess whether the cross-cultural equivalence of the Organisational Culture Survey (OCS) persist in an Australian context. The nature of the instrument is presented which includes a clear statement of its South African origin and its’ place within a logical positivist paradigm. The sample consisted of 326 respondents from a population of managers of the Australian Institute of Management. This study confirms the instrument’s validity and internal consistency within an Australian context, but that further research is required into the functional and conceptual equivalence of the survey items and dimensions underpinning the items to conclusively establish its utility. Finally, aspects of the ‘organisational culture’ construct underlying the survey need revision given recent trends in related systems, complexity and chaos theories. Opsomming Technikons propageer die beoefening van ko˛peratiewe onderwys,’n opvoedkundige strategiewat leer deur produktiewewerkservaring integreermet die teoretiese kurrikulum. ByTechnikon SAegter, het slegs sowat 35% van die formele programme ’n verpligte leerervarings komponent.Teoretiese-begrondings navorsingsmetodologie is gebruik omsekere basiese veronderstellings van akademiese personeel te bepaal. Eerder as om’n spesifieke navorsingsprobleemas vertrekpunt te gebruik, ondersoek teoretiese-begronding’n areavan belang en laat die metodiek die relevante sake toe omte voorskyn te kom. Semi-gestruktureerde onderhoude,met vier ope vrae, is gevoer met ’n gestratifiseerde eweskansige steekproef van 25 akademiese personeellede vanTechnikon SA. Daar is bevind dat alhoewel daar beperkte oortuiging en gewillige uitlewing van kooperatiewe onderwys is, is dit nie beduidend as kenmerkend van die organisasie kultuur vanTechnikon SA nie.

BACKGROUND: Channelling the development of haematopoietic progenitor cells into T lymphocytes is dependent upon a series of extrinsic prompts whose temporal and spatial sequence is critical for a productive outcome. Simple models of human progenitor cells development depend in the main on the use of xenogeneic systems which may provide some limitations to development. METHODS AND FINDINGS: Here we provide evidence that a simple model system which utilises both human keratinocyte and fibroblast cell lines arrayed on a synthetic tantalum coated matrix provides a permissive environment for the development of human CD34⁺ haematopoietic cells into mature CD4⁺ or CD8⁺ T lymphocytes in the presence of Interleukin 7 (IL-7), Interleukin 15 (IL-15) and the Fms-like tyrosine kinase 3 ligand (Flt-3L). This system was used to compare the ability of CD34(+) cells to produce mature thymocytes and showed that whilst these cells derived from cord blood were able to productively differentiate into thymocytes the system was not permissive for the development of CD34(+) cells from adult peripheral blood. CONCLUSIONS/SIGNIFICANCE: Our study provides direct evidence for the capacity of human cord blood CD34(+) cells to differentiate along the T lineage in a simple human model system. Productive commitment of the CD34⁺ cells to generate T cells was found to be dependent on a three-dimensional matrix which induced the up-regulation of the Notch delta-like ligand 4 (Dll-4) by epithelial cells.