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Liver transplantation (LT) from donors-with-HIV to recipients-with-HIV (HIV D+/R+) is permitted under the HOPE Act. There are only three international single-case reports of HIV D+/R+ LT, each with limited follow-up. We performed a prospective multicenter pilot study comparing HIV D+/R+ to donors-without-HIV to recipients-with-HIV (HIV D-/R+) LT. We quantified patient survival, graft survival, rejection, serious adverse events (SAEs), human immunodeficiency virus (HIV) breakthrough, infections, and malignancies, using Cox and negative binomial regression with inverse probability of treatment weighting. Between March 2016-July 2019, there were 45 LTs (8 simultaneous liver-kidney) at 9 centers: 24 HIV D+/R+, 21 HIV D-/R+ (10 D- were false-positive). The median follow-up time was 23 months. Median recipient CD4 was 287 cells/µL with 100% on antiretroviral therapy; 56% were hepatitis C virus (HCV)-seropositive, 13% HCV-viremic. Weighted 1-year survival was 83.3% versus 100.0% in D+ versus D- groups (p = .04). There were no differences in one-year graft survival (96.0% vs. 100.0%), rejection (10.8% vs. 18.2%), HIV breakthrough (8% vs. 10%), or SAEs (all p .05). HIV D+/R+ had more opportunistic infections, infectious hospitalizations, and cancer. In this multicenter pilot study of HIV D+/R+ LT, patient and graft survival were better than historical cohorts, however, a potential increase in infections and cancer merits further investigation.

To address shortcomings of the moderate-seismic design philosophy currently implemented in the United States, this paper proposes design criteria for a Concentrically Braced Dual Frame (CBDF). In contrast to existing low-ductility Concentrically Braced Frame (CBF) systems, such as R = 3 CBF (R3CBF) and Ordinary Concentrically Braced Frame (OCBF) systems, the proposed CBDF design approach explicitly considers the strength and integrity of the post-elastic, degraded (reserve) system. Specifically, the CBDF is defined to consist of a stiff low-ductility primary concentrically braced frame (PCBF) supplemented by a flexible, distributed reserve moment-resisting frame (RMRF). Relative to the R3CBF and OCBF systems, the proposed CBDF system achieves superior collapse performance without the need for costly ductility detailing requirements or substantial changes to traditional seismic design provisions. Consequently, the CBDF system is proposed as a practical, reliable, and cost-effective design alternative to R3CBF and OCBF systems.

Hair loss disorders may cause considerable distress to patients. Although many do not pose a significant medical risk, the sociocultural importance of hair is substantial. Often the extent of hair loss does not correlate to the impact on psychosocial function, thus necessitating an individualized approach. Hair loss disorders are interrelated with mental health and at times exert significant psychological percussions, and therefore, providers should address both medical and psychological aspects of treatment. This review contains a discussion of the impact on quality of life of common hair loss disorders and the psychological approaches that providers may utilize to improve care. The incorporation of psychodermatology and psychotrichology in dermatology and psychiatry residency programs is of vital importance. Dermatology and psychiatry liaison clinics may prove useful in the treatment of these patients.

We conducted an updated systematic review and meta-analysis on maternal outcomes associated with uterine exteriorization compared with in situ repair in women undergoing Cesarean delivery. We searched for randomized controlled trials comparing uterine exteriorization with in situ repair during Cesarean delivery. Primary outcomes were intraoperative nausea and vomiting (IONV) and perioperative decrease in hemoglobin concentration. Secondary outcomes were postoperative nausea and vomiting (PONV), estimated blood loss, fever, endometritis, wound infection, intraoperative and postoperative pain, postoperative analgesic use, duration of surgery and hospital stay, and time to return of bowel function. Twenty studies with 20,909 parturients were included. Exteriorization was associated with higher risk of IONV (odds ratio [OR], 2.09; 95% confidence interval [CI], 1.66 to 2.63; I2 = 0%), with no difference in perioperative hemoglobin concentration decrease (mean difference, − 0.06 g·dL-1; 95% CI, − 0.20 to 0.08; I2 = 97%) compared with in situ repair. There were no significant differences in estimated blood loss, transfusion requirement, PONV, duration of surgery, duration of hospital stay, time to return of bowel function, fever, endometritis, or wound infection. Postoperative pain (incidence of pain graded > 5/10) at six hours (OR, 1.64; 95% CI, 1.31 to 2.03; I2 = 0%) was higher with exteriorization, but there was no difference in need for rescue analgesia (OR, 2.48; 95% CI, 0.89 to 6.90; I2 = 94%) or pain scores at 24 hr compared with in situ repair. In this updated systematic review and meta-analysis, uterine exteriorization was associated with an increased risk of IONV but no significant change in perioperative hemoglobin decrease compared with in situ repair. PROSPERO (CRD42020190074); registered 5 July 2020.

Echinobase (www.echinobase.org) is a third generation web resource supporting genomic research on echinoderms. The new version was built by cloning the mature Xenopus model organism knowledgebase, Xenbase, refactoring data ingestion pipelines and modifying the user interface to adapt to multispecies echinoderm content. This approach leveraged over 15 years of previous database and web application development to generate a new fully featured informatics resource in a single year. In addition to the software stack, Echinobase uses the private cloud and physical hosts that support Xenbase. Echinobase currently supports six echinoderm species, focused on those used for genomics, developmental biology and gene regulatory network analyses. Over 38 000 gene pages, 18 000 publications, new improved genome assemblies, JBrowse genome browser and BLAST + services are available and supported by the development of a new echinoderm anatomical ontology, uniformly applied formal gene nomenclature, and consistent orthology predictions. A novel feature of Echinobase is integrating support for multiple, disparate species. New genomes from the diverse echinoderm phylum will be added and supported as data becomes available. The common code development design of the integrated knowledgebases ensures parallel improvements as each resource evolves. This approach is widely applicable for developing new model organism informatics resources.

While developments in cancer therapeutics have greatly reduced morbidity and mortality in females with breast cancer, it comes at a cost of an increased risk of cardiovascular complications. In particular, anthracyclines, like doxorubicin, which are a mainstay of current chemotherapy regimens, are associated with dose-dependent cardiotoxicity. Exercise has been widely accepted as an effective intervention in reducing cardiovascular risk in a variety of different clinical conditions. However, the benefits of exercise in anthracycline-mediated cardiotoxicity are not clearly understood. First, this review discusses the pre-clinical studies which have elucidated the cardioprotective mechanisms of aerobic and resistance exercise in improving cardiovascular function in the setting of anthracycline treatment. Next, it aims to summarize the results of aerobic and resistance exercise clinical trials conducted in females with breast cancer who received anthracycline-based chemotherapy. The review further discusses the current exercise guidelines for women undergoing chemotherapy and contraindications for exercise. Finally, the review addresses gaps in research, specifically the need for further clinical trials to establish a recommended exercise prescription within this patient population.

Dysnatremias are a rare but significant event in liver transplantation. While recipient pre-transplant hypernatremia has been demonstrated to increase post-transplant mortality, the degree of hypernatremia and the impact of its resolution have been less well characterized. Here, we used multivariate Cox regression with a comprehensive list of donor and recipient factors in order to conduct a robust multivariate retrospective database study of 54,311 United Network for Organ Sharing (UNOS) liver transplant patients to analyze the effect of pre-transplant serum sodium on post-transplant mortality, post-transplant length of hospitalization, and post-transplant graft survival. Mortality and graft failure increased in a stepwise fashion with increasing pre-transplant hypernatremia: 145 -150 mEq/L (HR = 1.118 and HR = 1.113), 150-155 mEq/L (HR = 1.324 and HR = 1.306), and > 155 mEq/L (HR = 1.623 and HR = 1.661). Pre-transplant hypo- and hypernatremia also increased length of post-transplant hospitalization: < 125 mEq/L (HR = 1.098), 125-130 mEq/L (HR = 1.060), 145 -150 mEq/L (HR = 1.140), and 150-155 mEq/L (HR = 1.358). Resolution of hypernatremia showed no significant difference in mortality compared with normonatremia, while unresolved hypernatremia significantly increased mortality (HR = 1.254), including a durable long-term increased mortality risk for patients with creatinine < 2 mg/dL and MELD < 25. Pre-transplant hypernatremia serves as a morbid prognostic indicator for post-transplant morbidity and mortality.

Background Organ transplantation from donors with human immunodeficiency virus (HIV) to recipients with HIV (HIV D+/R+) presents risks of donor-derived infections. Understanding clinical, immunologic, and virologic characteristics of HIV-positive donors is critical for safety. Methods We performed a prospective study of donors with HIV-positive and HIV false-positive (FP) test results within the HIV Organ Policy Equity (HOPE) Act in Action studies of HIV D+/R+ transplantation (ClinicalTrials.gov NCT02602262, NCT03500315, and NCT03734393). We compared clinical characteristics in HIV-positive versus FP donors. We measured CD4 T cells, HIV viral load (VL), drug resistance mutations (DRMs), coreceptor tropism, and serum antiretroviral therapy (ART) detection, using mass spectrometry in HIV-positive donors. Results Between March 2016 and March 2020, 92 donors (58 HIV positive, 34 FP), representing 98.9% of all US HOPE donors during this period, donated 177 organs (131 kidneys and 46 livers). Each year the number of donors increased. The prevalence of hepatitis B (16% vs 0%), syphilis (16% vs 0%), and cytomegalovirus (CMV; 91% vs 58%) was higher in HIV-positive versus FP donors; the prevalences of hepatitis C viremia were similar (2% vs 6%). Most HIV-positive donors (71%) had a known HIV diagnosis, of whom 90% were prescribed ART and 68% had a VL Conclusion The use of HIV-positive donor organs is increasing. HIV DRMs are common, yet resistance that would compromise integrase strand transfer inhibitor–based regimens is rare, which is reassuring regarding safety.

This post hoc analysis of the Adaptive Coronavirus Disease 2019 (COVID-19) Treatment Trial-1 (ACTT-1) shows a treatment effect of remdesivir (RDV) on progression to invasive mechanical ventilation (IMV) or death. Additionally, we create a risk profile that better predicts progression than baseline oxygen requirement alone. The highest risk group derives the greatest treatment effect from RDV.

Background Campylobacter spp. cause mostly self-limiting enterocolitis, although a significant proportion of cases require hospitalisation highlighting potential for severe disease. Among people admitted, blood culture specimens are frequently collected and antibiotic treatment is initiated. We sought to understand clinical and host factors associated with bacteraemia, antibiotic treatment and isolate non-susceptibility among Campylobacter-associated hospitalisations. Methods Using linked hospital microbiology and administrative data we identified and reviewed Campylobacter-associated hospitalisations between 2004 and 2013. We calculated population-level incidence for Campylobacter bacteraemia and used logistic regression to examine factors associated with bacteraemia, antibiotic treatment and isolate non-susceptibility among Campylobacter-associated hospitalisations. Results Among 685 Campylobacter-associated hospitalisations, we identified 25 admissions for bacteraemia, an estimated incidence of 0.71 cases per 100,000 population per year. Around half of hospitalisations (333/685) had blood culturing performed. Factors associated with bacteraemia included underlying liver disease (aOR 48.89, 95% CI 7.03–340.22, p p = 0.001) and age 70–79 years (aOR 4.93, 95% CI 1.57–15.49). Approximately one-third (219/685) of admissions received antibiotics with treatment rates increasing significantly over time (p p p p = 0.02). Non-susceptibility of isolates to standard antimicrobials increased significantly over time (p = 0.01) and was associated with overseas travel (aOR 11.80 95% CI 3.18–43.83, p p = 0.02), suggesting a healthy traveller effect. Conclusions Campylobacter infections result in considerable hospital burden. Among those admitted to hospital, an interplay of factors involving clinical presentation, presence of underlying comorbidities, complications and increasing age influence how a case is investigated and managed.

Modern changes in warfare have shown an increased incidence of lumbar spine injuries caused by underbody blast events. The susceptibility of the lumbar spine during these scenarios could be exacerbated by coupled moments that act with the rapid compressive force depending on the occupant’s seated posture. In this study, a combined loading lumbar spine vertebral body fracture injury criteria (Lic) across a range of postures was established from 75 tests performed on instrumented cadaveric lumbar spine specimens. The spines were predominantly exposed to axial compressive forces from an upward vertical thrust with 64 of the tests resulting in at least one vertebral body fracture and 11 in no vertebral body injury. The proposed Lic utilizes a recommended metric (κ), based on prismatic beam failure theory, resulting from the combination of the T12-L1 resultant sagittal force and the decorrelated bending moment with optimized critical values of Fr,crit = 5824 N and My,crit = 1155 Nm. The 50% risk of lumbar spine injury corresponded to a combined metric of 1, with the risk decreasing with the combined metric value. At 50% injury risk the Normalized Confidence Interval Size improved from 0.24 of a force-based injury reference curve to 0.17 for the combined loading metric.

OBJECTIVE Researchers have found a variety of uses for the Hybrid III (HIII) dummy that fall beyond the scope of its original purpose as an automotive crash test dummy. Some of these expanded roles for the HIII introduce situations that were not envisioned in the dummy's original design parameters, such as a relatively rapid succession of tests or outdoor testing scenarios where temperature is not easily controlled. This study investigates how the axial compressive stiffness of the HIII lumbar spine component is affected by the duration of the time interval between tests. Further, it measures the effect of temperature on the compressive stiffness of the lumbar spine through a range of temperatures relevant to indoor and outdoor testing. METHODS High-rate axial compression tests were run on a 50th percentile male HIII lumbar component in a materials testing machine. To characterize the effects of tests recovery intervals, between-test recovery was varied from 2 hours to 1 minute. To quantify temperature effects, environmental temperature conditions of 12.5°, 25°, and 37.5 °C were tested. RESULTS During repeated compressive loading, the force levels decreased consistently across long and short rest intervals. Even after 2 hours of rest between tests, full viscoelastic recovery was not observed. Temperature effects were pronounced, resulting in compressive force differences of 261% over the range of 12.5° to 37.5 °C. Compared to the stiffness of the lumbar at 25 °C, the stiffness at 37.5 °C fell by 40%; at 12.5 °C, the stiffness more than doubled, increasing by 115%. CONCLUSIONS A modest decrease in temperature can be sufficient to dramatically change the response and repeatability of the lumbar HIII component in compressive loading. The large magnitude of the temperature effect has severe implications in its ability to overwhelm the contributions of targeted test variables. These findings highlight the importance of controlling, monitoring and reporting temperature conditions during HIII testing, even in indoor laboratory environments.

SUMMARYIt is generally believed that the physiological consequences of stress could contribute to poor outcomes for patients being treated for cancer. However, despite preclinical and clinical evidence suggesting that stress promotes increased cancer-related mortality, a comprehensive understanding of the mechanisms involved in mediating these effects does not yet exist. We reviewed 47 clinical studies published between 2007 and 2020 to determine whether psychosocial stress affects clinical outcomes in cancer: 6.4% of studies showed a protective effect; 44.6% showed a harmful effect; 48.9% showed no association. These data suggest that psychosocial stress could affect cancer incidence and/or mortality, but the association is unclear. To shed light on this potentially important relationship, objective biomarkers of stress are needed to more accurately evaluate levels of stress and its downstream effects. As a potential candidate, the neuroendocrine signalling pathways initiated by stress are known to affect anti-tumour immune cells, and here we summarise how this may promote an immunosuppressive, pro-tumour microenvironment. Further research must be done to understand the relationships between stress and immunity to more accurately measure how stress affects cancer progression and outcome.

The SARS-CoV2 pandemic has resulted in the deaths of more than 600,000 Americans to date, and millions more worldwide. The rapid development of multiple vaccines with exceedingly high (>90%) efficacy at preventing death from SARS-CoV2 is one of the recent miracles of medicine. Early vaccination efforts targeted those with the highest risk of contracting and/or dying from SARS-CoV2, including the elderly and those with chronic medical conditions (e.g., cancer, immunosuppression).

BACKGROUND: Severe coronavirus disease 2019 (Covid-19) is associated with dysregulated inflammation. The effects of combination treatment with baricitinib, a Janus kinase inhibitor, plus remdesivir are not known.METHODS: We conducted a double-blind, randomized, placebo-controlled trial evaluating baricitinib plus remdesivir in hospitalized adults with Covid-19. All the patients received remdesivir (≤10 days) and either baricitinib (≤14 days) or placebo (control). The primary outcome was the time to recovery. The key secondary outcome was clinical status at day 15.RESULTS: A total of 1033 patients underwent randomization (with 515 assigned to combination treatment and 518 to control). Patients receiving baricitinib had a median time to recovery of 7 days (95% confidence interval [CI], 6 to 8), as compared with 8 days (95% CI, 7 to 9) with control (rate ratio for recovery, 1.16; 95% CI, 1.01 to 1.32; P = 0.03), and a 30% higher odds of improvement in clinical status at day 15 (odds ratio, 1.3; 95% CI, 1.0 to 1.6). Patients receiving high-flow oxygen or noninvasive ventilation at enrollment had a time to recovery of 10 days with combination treatment and 18 days with control (rate ratio for recovery, 1.51; 95% CI, 1.10 to 2.08). The 28-day mortality was 5.1% in the combination group and 7.8% in the control group (hazard ratio for death, 0.65; 95% CI, 0.39 to 1.09). Serious adverse events were less frequent in the combination group than in the control group (16.0% vs. 21.0%; difference, -5.0 percentage points; 95% CI, -9.8 to -0.3; P = 0.03), as were new infections (5.9% vs. 11.2%; difference, -5.3 percentage points; 95% CI, -8.7 to -1.9; P = 0.003).CONCLUSIONS: Baricitinib plus remdesivir was superior to remdesivir alone in reducing recovery time and accelerating improvement in clinical status among patients with Covid-19, notably among those receiving high-flow oxygen or noninvasive ventilation. The combination was associated with fewer serious adverse events. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT04401579.).

BACKGROUND: Narrative letters of recommendation are an important component of the residency application process. However, because narrative letters of recommendation are almost always positive, it is unclear whether those reviewing the letters understand the writer’s intended strength of support for a given applicant. QUESTIONS/PURPOSES: (1) Is the perception of letter readers for narrative letters of recommendation consistent with the intention of the letter’s author? (2) Is there inter-reviewer consistency in selection committee members’ perceptions of the narrative letters of recommendation? METHODS: Letter writers who wrote two or more narrative letters of recommendation for applicants to one university-based orthopaedic residency program for the 2014 to 2015 application cycle were sent a survey linked to a specific letter of recommendation they authored to assess the intended meaning regarding the strength of an applicant. A total of 247 unstructured letters of recommendation and accompanying surveys were sent to their authors, and 157 surveys were returned and form the basis of this study (response percentage 64%). The seven core members of the admissions committee (of 22 total reviewers) at a university-based residency program were sent a similar survey regarding their perception of the letter. To answer our research question about whether letter readers’ perceptions about a candidate were consistent with the letter writer’s intention, we used kappa values to determine agreement for survey questions involving discrete variables and Spearman correlation coefficients (SCCs) to determine agreement for survey questions involving continuous variables. To answer our research question regarding inter-reviewer consistency among the seven faculty members, we compared the letter readers’ responses to each survey question using intraclass correlation coefficients (ICCs). RESULTS: There was a negligible to moderate correlation between the intended and perceived strength of the letters (SCC 0.26 to 0.57), with only one of seven letter readers scoring in the moderate correlation category. When stratifying the applicants into thirds, there was only slight agreement (kappa 0.07 to 0.19) between the writers and reviewers. There were similarly low kappa values for agreement about how the writers and readers felt regarding the candidate matching into their program (kappa 0.14 to 0.30). The ICC for each question among the seven faculty reviewers ranged from poor to moderate (ICC 0.42 to 0.52). CONCLUSION: Our results demonstrate that the reader’s perception of narrative letters of recommendation did not correlate well with the letter writer’s intended meaning and was not consistent between letter readers at a single university-based urban orthopaedic surgery residency program. CLINICAL RELEVANCE: Given the low correlation between the intended strength of the letter writers and the perceived strength of those letters, we believe that other options such as a slider bar or agreed-upon wording as is used in many dean’s letters may be helpful.

Background There are no antiviral therapies for parainfluenza virus (PIV) infections. DAS181, a sialidase fusion protein, has demonstrated activity in in vitro and in animal models of PIV. Methods Adult immunocompromised patients diagnosed with PIV lower respiratory tract infection (LRTI) who required oxygen supplementation were randomized 2:1 to nebulized DAS181 (4.5 mg/day) or matching placebo for up to 10 days. Randomization was stratified by need for mechanical ventilation (MV) or supplemental oxygen (SO). The primary endpoint was the proportion of patients reaching clinical stability survival (CSS) defined as returning to room air (RTRA), normalization of vital signs for at least 24 hours, and survival up to day 45 from enrollment. Results A total of 111 patients were randomized to DAS181 (n = 74) or placebo (n = 37). CSS was achieved by 45.0% DAS181-treated patients in the SO stratum compared with 31.0% for placebo (P = .15), whereas patients on MV had no benefit from DAS181. The proportion of patients achieving RTRA was numerically higher for SO stratum DAS181 patients (51.7%) compared with placebo (34.5%) at day 28 (P = .17). In a post hoc analysis of solid organ transplant, hematopoietic cell transplantation within 1 year, or chemotherapy within 1 year, more SO stratum patients achieved RTRA on DAS181 (51.8%) compared with placebo (15.8%) by day 28 (P = .012). Conclusions The primary endpoint was not met, but post hoc analysis of the RTRA component suggests DAS181 may have clinical activity in improving oxygenation in select severely immunocompromised patients with PIV LRTI who are not on mechanical ventilation. Clinical Trials Registration. NCT01644877., Immunocompromised adults with severe parainfluenza received nebulized DAS181 or placebo for up to 10 days. The primary endpoint was not met, but a subgroup of severely immunocompromised patients experienced a faster return to room air by day 28 (P = .012).

To safely resume sports, college and university athletic programs and regional athletic conferences created plans to mitigate transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). Mitigation measures included physical distancing, universal masking, and maximizing outdoor activity during training; routine testing; 10-day isolation of persons with COVID-19; and 14-day quarantine of athletes identified as close contacts* of persons with confirmed COVID-19. Regional athletic conferences created testing and quarantine policies based on National Collegiate Athletic Association (NCAA) guidance (1); testing policies varied by conference, school, and sport. To improve compliance with quarantine and reduce the personal and economic burden of quarantine adherence, the quarantine period has been reduced in several countries from 14 days to as few as 5 days with testing (2) or 10 days without testing (3). Data on quarantined athletes participating in NCAA sports were used to characterize COVID-19 exposures and assess the amount of time between quarantine start and first positive SARS-CoV-2 test result. Despite the potential risk for transmission from frequent, close contact associated with athletic activities (4), more athletes reported exposure to COVID-19 at social gatherings (40.7%) and from roommates (31.7%) than they did from exposures associated with athletic activities (12.7%). Among 1,830 quarantined athletes, 458 (25%) received positive reverse transcription-polymerase chain reaction (RT-PCR) test results during the 14-day quarantine, with a mean of 3.8 days from quarantine start (range = 0-14 days) until the positive test result. Among athletes who had not received a positive test result by quarantine day 5, the probability of having a positive test result decreased from 27% after day 5 to

Severe headache is a hallmark clinical feature of spontaneous subarachnoid hemorrhage (SAH), affecting nearly 90% of patients during index hospitalization, regardless of the SAH severity or presence of a culprit aneurysm. Up to 1 in 4 survivors of SAH experience chronic headaches, which may be severe and last for years. Data guiding the optimal management of post-SAH headache are lacking. Opioids, often in escalating doses, remain the guideline-recommended mainstay of acute therapy, but pain relief remains suboptimal. This study is a case series of adult patients who received bilateral pterygopalatine fossa (PPF) blockade for the management of refractory headaches after spontaneous SAH (aneurysmal and non-aneurysmal) at a single tertiary care center. We examined pain scores and analgesic requirements before and after block placement. Seven patients (median age 54 years, 3 men, four aneurysmal and three non-aneurysmal) received a PPF-block between post-bleed day 6–11 during index hospitalization in the neurointensive care unit. The worst pain recorded in the 24-h period before the block was significantly higher than in the period 4 h after the block (9.1 vs. 3.1; p = 0.0156), and in the period 8 h after the block (9.1 vs. 2.8; p = 0.0313). The only complication was minor oozing from the needle insertion sites, which subsided completely with gauze pressure within 1 min. PPF blockade might constitute a promising opioid-sparing therapeutic strategy for the management of post-SAH headache that merits further prospective controlled randomized studies.

BACKGROUND: Exposure of respiratory therapists (RTs) during aerosol-generating procedures such as endotracheal intubation is an occupational hazard. Depending on the hospital, RTs may serve as laryngoscopist or in a role providing ventilation support and initiating mechanical ventilation. This study aimed to evaluate the potential exposure of RTs serving in either of these roles. METHODS: We set up a simulated patient with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in an ICU setting requiring endotracheal intubation involving a laryngoscopist, a nurse, and an RT supporting the laryngoscopist. All participants wore appropriate personal protective equipment (PPE). A fluorescent marker was sprayed by an atomizer during the procedure using 3 different methods for endotracheal intubation. The 3 techniques included PPE alone, a polycarbonate intubating box, or a coronavirus flexible enclosure, which consisted of a Mayo stand with plastic covering. The laryngoscopist and the supporting RT were assessed with a black light for contamination with the fluorescent marker. All simulations were recorded. RESULTS: When using only PPE, both the laryngoscopist and the RT were grossly contaminated. When using the intubating box, the laryngoscopist’s contamination was detectable only on the gloves: the gown and face shield remained uncontaminated; the RT was still grossly contaminated on the gloves, gown, neck, and face shield. When using the coronavirus flexible enclosure system, both the laryngoscopist and the RT were better protected, with contamination detected only on the gloves of the laryngoscopist and the RT. CONCLUSIONS: Of the 3 techniques, the coronavirus flexible enclosure contained the fluorescent marker more effectively during endotracheal intubation than PPE alone or the intubating box based on exposure of the laryngoscopist and supporting RT. Optimizing containment during aerosol-generating procedures like endotracheal intubation is a critical component of minimizing occupational and nosocomial spread of SARS-CoV-2 to RTs who may serve as either the laryngoscopist or a support role.

Use of cannabidiol (CBD) products has become widespread due to the proposed medical benefits without the “high” of marijuana, with recent polling indicating that 1 in 7 Americans report using a CBD product. However, health care professionals have apprehension about whether these treatments are legal, safe, and effective. In this review, we provide a summary of the scientific evidence on CBD oil so that a nurse practitioner can guide patients to the safest and most beneficial products within today’s regulatory environment.

Severe acute pancreatitis (SAP) includes persistent systemic inflammation (SIRS) and multiorgan failure (MOF). The mechanism of transition from SIRS to MOF is unclear. We developed a fluid compartment model and used clinical data to test predictions. The model includes vascular, interstitial and “third-space” compartments with variable permeability of plasma proteins at the capillaries. Consented patients from University of Pittsburgh Medical Center Presbyterian Hospital were studied. Preadmission and daily hematocrit (HCT), blood urea nitrogen (BUN), creatine (Cr), albumin (Alb), and total protein (TP) were collected, and nonalbumin plasma protein (NAPP = TP minus the Alb) was calculated. Subjects served as their own controls for trajectory analysis. Of 57 SAP subjects, 18 developed MOF (5 died), and 39 were non-MOF (0 died). Compared with preadmission levels, admission HCT increased in MOF +5.00 [25%-75% interquartile range, IQR] versus non-MOF −0.10 [−1.55, 1.40] (P < 0.002) with HCT > +3 distinguishing MOF from non-MOF (odds ratio 17.7, P = 0.014). Preadmission Alb fell faster in MOF than non-MOF (P < 0.01). By day 2, TP and NAPP dropped in MOF but not non-MOF (P < 0.001). BUN and Cr levels increased in MOF (P = 0.001), but BUN-to-Cr ratios remained constant. Pancreatic necrosis was more common in MOF (56%) than non-MOF (23%). Changing capillary permeability to allow loss of NAPP in this model predicts loss of plasma oncotic pressure and reduced vascular volume, hypotension with prerenal azotemia and acute kidney dysfunction, pancreas necrosis, and pulmonary edema from capillary leak in the lung with acute respiratory distress syndrome. Sequential biomarker analysis in humans with or without MOF is consistent with this model. This study is registered on https://clinicaltrials.gov at NCT03075605. NEW & NOTEWORTHY Acute pancreatitis is a sudden inflammatory response to pancreatic injury that may spread to systemic inflammation, multiorgan failure, and death in some patients. With the use of the predictions of a new mechanistic model, we compared patients with severe acute pancreatitis with or without multiorgan failure. All biomarkers of capillary leak and clinical features of multiorgan failure were accurately predicted. This provides a new paradigm for understanding and developing new treatments for patients with severe acute pancreatitis.

Patients who suffer an unintentional dural puncture have a high risk of developing a post-dural puncture headache. Other neurologic complications have been reported, but seizure is rarely seen. We present a case of a 21-year-old primigravida who experienced an unrecognized unintentional dural puncture that ultimately resulted in a tonic-clonic seizure from intracranial hypotension one week following the dural breach. Her trachea was intubated and she was transferred to the intensive care unit. Two epidural blood patches, performed by neuroradiologists, were needed before the patient experienced complete resolution of her headache. During the re-admission, she also experienced a pulmonary embolus which further lengthened her hospital stay.

BACKGROUND Although the combination of doxorubicin (DOX) and trastuzumab (TRZ) reduces the progression and recurrence of breast cancer, these anticancer drugs are associated with significant cardiotoxic side effects. OBJECTIVE We investigated whether prophylactic administration of flaxseed (FLX) and its bioactive components, α-linolenic acid (ALA) and secoisolariciresinol diglucoside (SDG), would be cardioprotective against DOX + TRZ-mediated cardiotoxicity in a chronic in vivo female murine model. METHODS Wild-type C57BL/6 female mice (10-12 wk old) received daily prophylactic treatment with one of the following diets: 1) regular control (RC) semi-purified diet; 2) 10% FLX diet; 3) 4.4% ALA diet; or 4) 0.44% SDG diet for a total of 6 wks. Within each arm, mice received 3 weekly injections of 0.9% saline or a combination of DOX [8 mg/(kg.wk)] and TRZ [3 mg/(kg.wk)] starting at the end of week 3. The main outcome was to evaluate the effects of FLX, ALA, and SDG on cardiovascular remodeling and markers of apoptosis, inflammation, and mitochondrial dysfunction. Significance between measurements was determined using a 4 (diet) × 2 (chemotherapy) × 2 (time) mixed factorial design with repeated measures. RESULTS In the RC + DOX + TRZ-treated mice at week 6 of the study, the left ventricular ejection fraction (LVEF) decreased by 50% compared with the baseline LVEF (P

This paper describes the development of convolutional neural networks (CNN), a type of deep-learning method, to predict next-hour tornado occurrence. Predictors are a storm-centered radar image and a proximity sounding from the Rapid Refresh model. Radar images come from the Multiyear Reanalysis of Remotely Sensed Storms (MYRORSS) and Gridded NEXRAD WSR-88D Radar dataset (GridRad), both of which are multiradar composites. We train separate CNNs on MYRORSS and GridRad data, present an experiment to optimize the CNN settings, and evaluate the chosen CNNs on independent testing data. Both models achieve an area under the receiver-operating-characteristic curve (AUC) well above 0.9, which is considered to be excellent performance. The GridRad model achieves a critical success index (CSI) of 0.31, and the MYRORSS model achieves a CSI of 0.17. The difference is due primarily to event frequency (percentage of storms that are tornadic in the next hour), which is 3.52% for GridRad but only 0.24% for MYRORSS. The best CNN predictions (true positives and negatives) occur for strongly rotating tornadic supercells and weak nontornadic cells in mesoscale convective systems, respectively. The worst predictions (false positives and negatives) occur for strongly rotating nontornadic supercells and tornadic cells in quasi-linear convective systems, respectively. The performance of our CNNs is comparable to an operational machine-learning system for severe weather prediction, which suggests that they would be useful for real-time forecasting.

Background Migraine surgery is an increasingly popular treatment option for migraine patients. The lesser occipital nerve is a common trigger point for headache abnormalities, but there is a paucity of research regarding the lesser occipital nerve and its intimate association with the spinal accessory nerve. Methods Six cadaver necks were dissected. The lesser occipital, great auricular, and spinal accessory nerves were identified and systematically measured and recorded. These landmarks included the longitudinal axis (vertical line drawn in the posterior), the horizontal axis (defined as a line between the most anterosuperior points of the external auditory canals) and the earlobe. Mean distances and standard deviations were calculated to delineate the relationship between the spinal accessory, lesser occipital, and great auricular nerves. Results The point of emergence of the spinal accessory nerve was determined to be 7.17 ± 1.15 cm lateral to the y axis and 7.77 ± 1.10 caudal to the x axis. The lesser occipital nerve emerges 7.5 ± 1.31 cm lateral to the y axis and 8.47 ± 1.11 cm caudal to the x axis. The great auricular nerve emerges 8.33 ± 1.31 cm lateral to the y axis and 9.4 ±1.07 cm caudal to the x axis. The decussation of the spinal accessory and the lesser occipital nerves was found to be 7.70 ± 1.16 cm caudal to the x axis and 7.17 ± 1.15 lateral to the y axis. Conclusion Understanding the close relationship between the lesser occipital nerve and spinal accessory nerve in the posterior, lateral neck area is crucial for a safer approach to occipital migraine headaches, occipital neuralgia, and new daily persistent headaches and other reconstructive or cosmetic operations.

Campylobacter spp. are a globally important cause of bacterial gastroenteritis, with Australia experiencing higher rates of illness than many comparable high-income countries. Despite the high disease incidence, outbreaks of campylobacteriosis in Australia are infrequently detected and reported. We examined the epidemiology of Campylobacter outbreaks in Australia, with particular emphasis on assessing transmission routes and evidence as reported during public health investigations. A national register of enteric and foodborne disease outbreaks was used to summarize data on all Campylobacter outbreaks reported in Australia between 2001 and 2016. Outbreak data were reviewed and analyzed for trends over time. Additional information was sought from state and territory epidemiologists, to validate transmission routes. A total of 84 Campylobacter outbreaks were reported, with 51 (61%) being classified as foodborne. Specific food vehicles were identified for 33 (65%) outbreaks, with 28 (85%) implicating chicken or chicken-containing dishes. Although no increase in the proportion of foodborne Campylobacter outbreaks was observed, examination of specific food vehicles demonstrated a significant increase in outbreaks because of poultry-liver containing foods (p = 0.04). One quarter of all 1042 outbreak-associated cases occurred in aged-care facilities (ACFs), including 17 associated hospitalizations and three deaths. After review of evidence data, 23 outbreaks (27%) were determined to have an unknown route of transmission, including 10 (43%) outbreaks occurring in ACFs. Campylobacter spp. remain a less commonly reported cause of gastroenteritis outbreaks in Australia. Although many reported outbreaks can be linked to foodborne transmission, over a quarter were unable to identify either a food vehicle or transmission source, particularly for outbreaks occurring in aged care. Increased efforts to improve evidence collection and understanding of transmission dynamics for outbreaks of campylobacteriosis, particularly in aged care, are required.

Introduction The authors provide an updated, systematic and comprehensive summary of the literature concerning management of the N0 neck in patients for whom primary irradiation for squamous cell carcinoma of the larynx has been unsuccessful and salvage surgery in the form of total laryngectomy (TL) advocated. Methods Bibliographic databases MEDLINE, Cochrane, PubMed and Embase were searched from inception to April 2019, with no language restrictions. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Risk of bias was defined using the Joanna Briggs Institute guidelines. Outcome measures were defined as the impact of END on locoregional control, complication rate, disease-specific and overall survival (DSS and OS). Results The primary search identified 19 eligible articles, comprising 1353 patients, (1552 ENDs). The overall risk of occult metastases was 14% (9% of ENDs). The relative risk (RR) of developing complications was 1.29 when END was performed, compared to observation of the neck (CI 0.86-1.92). Contrariwise, patients in whom the neck was managed with neck dissection had a decreased risk of developing regional recurrence (RR 0.62, CI 0.35-1.08). There was no statistically significant variation between DSS and OS between END and neck observation groups, respectively. Summary END during salvage TL may reduce the rate of regional recurrence, but not at the expense of improving DSS or OS. Rates of occult metastases, regional recurrence and "cure" through salvage neck dissection are not equivalent. Significant bias in all collated manuscripts should encourage the reader to interpret conclusions with caution. Patients should be fully involved in the decision-making process and their performance status and co-morbidities taken carefully into account when deciding to increase the extent of surgery, which we believe should remain limited to TL in the majority of cases.

Background We recently mitigated a clonal outbreak of hospital-acquired Mycobacterium abscessus complex (MABC), which included a large cluster of adult patients who developed invasive infection after exposure to heater-cooler units during cardiac surgery. Recent studies have detailed Mycobacterium chimaera infections acquired during cardiac surgery; however, little is known about the epidemiology and clinical courses of cardiac surgery patients with invasive MABC infection. Methods We retrospectively collected clinical data on all patients who underwent cardiac surgery at our hospital and subsequently had positive cultures for MABC from 2013 through 2016. Patients with ventricular assist devices or heart transplants were excluded. We analyzed patient characteristics, antimicrobial therapy, surgical interventions, and clinical outcomes. Results Ten cardiac surgery patients developed invasive, extrapulmonary infection from M. abscessus subspecies abscessus in an outbreak setting. Median time from presumed inoculation in the operating room to first positive culture was 53 days (interquartile range [IQR], 38–139 days). Disseminated infection was common, and the most frequent culture-positive sites were mediastinum (n = 7) and blood (n = 7). Patients received a median of 24 weeks (IQR, 5–33 weeks) of combination antimicrobial therapy that included multiple intravenous agents. Six patients required antibiotic changes due to adverse events attributed to amikacin, linezolid, or tigecycline. Eight patients underwent surgical management, and 6 patients required multiple sternal debridements. Eight patients died within 2 years of diagnosis, including 4 deaths directly attributable to MABC infection. Conclusions Despite aggressive medical and surgical management, invasive MABC infection after cardiac surgery caused substantial morbidity and mortality. New treatment strategies are needed, and compliance with infection prevention guidelines remains critical.

Chronic infection provokes alterations in inflammatory and suppressive pathways that potentially affect the function and integrity of multiple tissues, impacting both ongoing immune control and restorative immune therapies. Here we demonstrate that chronic lymphocytic choriomeningitis virus infection rapidly triggers severe thymic depletion, mediated by CD8 T cell-intrinsic type I interferon (IFN) and signal transducer and activator of transcription 2 (Stat2) signaling. Occurring temporal to T cell exhaustion, thymic cellularity reconstituted despite ongoing viral replication, with a rapid secondary thymic depletion following immune restoration by anti-programmed death-ligand 1 (PDL1) blockade. Therapeutic hematopoietic stem cell transplant (HSCT) during chronic infection generated new antiviral CD8 T cells, despite sustained virus replication in the thymus, indicating an impairment in negative selection. Consequently, low amounts of high-affinity self-reactive T cells also escaped the thymus following HSCT during chronic infection. Thus, by altering the stringency and partially impairing negative selection, the host generates new virus-specific T cells to replenish the fight against the chronic infection, but also has the potentially dangerous effect of enabling the escape of self-reactive T cells.

The study of marginal liver transplant outcomes, including post-transplant length of stay (LOS), is necessary for determining the practicality of their use. 50,155 patients who received transplants from 2012 to 2020 were retrospectively analyzed with data from the Scientific Registry of Transplant Recipients database using Kaplan-Meier survival curves and multivariable Cox regression. Six different definitions were used to classify an allograft as being marginal: 90th percentile Donor Risk Index allografts, donation after cardiac death donors, national share donors, donors over 70, donors with >30% macrovesicular steatosis, or 90th percentile Discard Risk Index donors. 24% (n = 12,124) of subjects received marginal allografts. Average LOS was 15.6 days among those who received standard allografts. Among those who received marginal allografts, LOS was found to be highest in those who received 90th percentile Donor Risk Index allografts at 15.6 days, and lowest in those who received donation after cardiac death allografts at 12.7 days. Apart from fatty livers (95% CI 0.86 - 0.98), marginal allografts were not associated with a prolonged LOS. We conclude that accounting for experience and recipient matching, transplant centers may be more aggressive in their use of extended criteria donors with limited fear of increasing LOS and its associated costs. This article is protected by copyright. All rights reserved.

Description, A rapid test measures neutralizing antibodies against SARS-CoV-2 variants of concern in 1 hour., Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are concerning in the ongoing coronavirus disease 2019 (COVID-19) pandemic. Here, we developed a rapid test, termed CoVariant-SCAN, that detects neutralizing antibodies (nAbs) capable of blocking interactions between the angiotensin-converting enzyme 2 receptor and the spike protein of wild-type (WT) SARS-CoV-2 and three other variants: B.1.1.7, B.1.351, and P.1. Using CoVariant-SCAN, we assessed neutralization/blocking of monoclonal antibodies and plasma from COVID-19–positive and vaccinated individuals. For several monoclonal antibodies and most plasma samples, neutralization against B.1.351 and P.1 variants is diminished relative to WT, while B.1.1.7 is largely cross-neutralized. We also showed that we can rapidly adapt the platform to detect nAbs against an additional variant—B.1.617.2 (Delta)—without reengineering or reoptimizing the assay. Results using CoVariant-SCAN are consistent with live virus neutralization assays and demonstrate that this easy-to-deploy test could be used to rapidly assess nAb response against multiple SARS-CoV-2 variants.

Background Many studies have been done on the strength and mobility of the shoulder and hip in baseball players, but fewer studies have examined these metrics in softball players. # Purpose The purpose of this study was to observe and analyze changes in range of motion (ROM) and strength at the hip and shoulder that occur over the course of a competitive season, to describe preseason ROM and strength at the hip and shoulder in healthy college softball players through side-to-side comparison, and to compare measurements between pitchers and position players. # Study Design Descriptive Cohort Study # Methods Data was collected over the course of six seasons, and a total of fifty-four healthy softball athletes (including pitchers and postiion players) who completed at least one set of preseason and postseason measurements were included. Subjects underwent passive ROM (External rotation \[ER\], internal rotation \[IR\], total arc of motion \[TAM\]) and strength (ER/IR at the shoulder, abduction/extension at the hip) measurements at preseason and postseason timepoints. # Results Over a season, position players demonstrated an increase in all ROM metrics in both shoulders, except dominant IR, and a decrease in ER strength at the shoulder bilaterally (p\

Summary Background Functional impairment of interferon, a natural antiviral component of the immune system, is associated with the pathogenesis and severity of COVID-19. We aimed to compare the efficacy of interferon beta-1a in combination with remdesivir compared with remdesivir alone in hospitalised patients with COVID-19. Methods We did a double-blind, randomised, placebo-controlled trial at 63 hospitals across five countries (Japan, Mexico, Singapore, South Korea, and the USA). Eligible patients were hospitalised adults (aged ≥18 years) with SARS-CoV-2 infection, as confirmed by a positive RT-PCR test, and who met one of the following criteria suggestive of lower respiratory tract infection: the presence of radiographic infiltrates on imaging, a peripheral oxygen saturation on room air of 94% or less, or requiring supplemental oxygen. Patients were excluded if they had either an alanine aminotransferase or an aspartate aminotransferase concentration more than five times the upper limit of normal; had impaired renal function; were allergic to the study product; were pregnant or breast feeding; were already on mechanical ventilation; or were anticipating discharge from the hospital or transfer to another hospital within 72 h of enrolment. Patients were randomly assigned (1:1) to receive intravenous remdesivir as a 200 mg loading dose on day 1 followed by a 100 mg maintenance dose administered daily for up to 9 days and up to four doses of either 44 μg interferon beta-1a (interferon beta-1a group plus remdesivir group) or placebo (placebo plus remdesivir group) administered subcutaneously every other day. Randomisation was stratified by study site and disease severity at enrolment. Patients, investigators, and site staff were masked to interferon beta-1a and placebo treatment; remdesivir treatment was given to all patients without masking. The primary outcome was time to recovery, defined as the first day that a patient attained a category 1, 2, or 3 score on the eight-category ordinal scale within 28 days, assessed in the modified intention-to-treat population, defined as all randomised patients who were classified according to actual clinical severity. Safety was assessed in the as-treated population, defined as all patients who received at least one dose of the assigned treatment. This trial is registered with ClinicalTrials.gov , NCT04492475 . Findings Between Aug 5, 2020, and Nov 11, 2020, 969 patients were enrolled and randomly assigned to the interferon beta-1a plus remdesivir group (n=487) or to the placebo plus remdesivir group (n=482). The mean duration of symptoms before enrolment was 8·7 days (SD 4·4) in the interferon beta-1a plus remdesivir group and 8·5 days (SD 4·3) days in the placebo plus remdesivir group. Patients in both groups had a time to recovery of 5 days (95% CI not estimable) (rate ratio of interferon beta-1a plus remdesivir group vs placebo plus remdesivir 0·99 [95% CI 0·87–1·13]; p=0·88). The Kaplan-Meier estimate of mortality at 28 days was 5% (95% CI 3–7%) in the interferon beta-1a plus remdesivir group and 3% (2–6%) in the placebo plus remdesivir group (hazard ratio 1·33 [95% CI 0·69–2·55]; p=0·39). Patients who did not require high-flow oxygen at baseline were more likely to have at least one related adverse event in the interferon beta-1a plus remdesivir group (33 [7%] of 442 patients) than in the placebo plus remdesivir group (15 [3%] of 435). In patients who required high-flow oxygen at baseline, 24 (69%) of 35 had an adverse event and 21 (60%) had a serious adverse event in the interferon beta-1a plus remdesivir group compared with 13 (39%) of 33 who had an adverse event and eight (24%) who had a serious adverse event in the placebo plus remdesivir group. Interpretation Interferon beta-1a plus remdesivir was not superior to remdesivir alone in hospitalised patients with COVID-19 pneumonia. Patients who required high-flow oxygen at baseline had worse outcomes after treatment with interferon beta-1a compared with those given placebo. Funding The National Institute of Allergy and Infectious Diseases (USA).

Key Points Question Are surveillance testing and quarantine still important for limiting virus transmission on college campuses where the student population is completely vaccinated against SARS-CoV-2? Findings In this decision analytical model study of 5000 simulated undergraduates, if 100% were vaccinated with 90% vaccine effectiveness, surveillance testing and quarantine were not associated with a substantial reduction in infections. However, if vaccine effectiveness was reduced to 75%, weekly surveillance testing was associated with a substantial reduction in the number of infections; at 50% vaccine effectiveness, surveillance testing and quarantine were associated with a marked reduction in the estimated number of infections. Meaning The study results suggest that surveillance testing and isolation of positive cases may remain important mitigation strategies on university campuses with a vaccinated student body with only modest erosion of vaccine effectiveness, while quarantining contacts offers limited added benefit over surveillance testing alone and may be effectively replaced by an increased testing cadence of reported contacts., Importance The importance of surveillance testing and quarantine on university campuses to limit SARS-CoV-2 transmission needs to be reevaluated in the context of a complex and rapidly changing environment that includes vaccines, variants, and waning immunity. Also, recent US Centers for Disease Control and Prevention guidelines suggest that vaccinated students do not need to participate in surveillance testing. Objective To evaluate the use of surveillance testing and quarantine in a fully vaccinated student population for whom vaccine effectiveness may be affected by the type of vaccination, presence of variants, and loss of vaccine-induced or natural immunity over time. Design, Setting, and Participants In this simulation study, an agent-based Susceptible, Exposed, Infected, Recovered model was developed with some parameters estimated using data from the 2020 to 2021 academic year at Duke University (Durham, North Carolina) that described a simulated population of 5000 undergraduate students residing on campus in residential dormitories. This study assumed that 100% of residential undergraduates are vaccinated. Under varying levels of vaccine effectiveness (90%, 75%, and 50%), the reductions in the numbers of positive cases under various mitigation strategies that involved surveillance testing and quarantine were estimated. Main Outcomes and Measures The percentage of students infected with SARS-CoV-2 each day for the course of the semester (100 days) and the total number of isolated or quarantined students were estimated. Results A total of 5000 undergraduates were simulated in the study. In simulations with 90% vaccine effectiveness, weekly surveillance testing was associated with only marginally reduced viral transmission. At 50% to 75% effectiveness, surveillance testing was estimated to reduce the number of infections by as much as 93.6%. A 10-day quarantine protocol for exposures was associated with only modest reduction in infections until vaccine effectiveness dropped to 50%. Increased testing of reported contacts was estimated to be at least as effective as quarantine at limiting infections. Conclusions and Relevance In this simulated modeling study of infection dynamics on a college campus where 100% of the student body is vaccinated, weekly surveillance testing was associated with a substantial reduction of campus infections with even a modest loss of vaccine effectiveness. Model simulations also suggested that an increased testing cadence can be as effective as a 10-day quarantine period at limiting infections. Together, these findings provide a potential foundation for universities to design appropriate mitigation protocols for the 2021 to 2022 academic year., This decision analytical model study examines the use of surveillance testing and quarantine in a fully COVID-19–vaccinated university student population.

Host biomarkers are increasingly being considered as tools for improved COVID-19 detection and prognosis. We recently profiled circulating host-encoded microRNA (miRNAs) during SARS-CoV-2 infection, revealing a signature that classified COVID-19 cases with 99.9% accuracy. Here we sought to develop a signature suited for clinical application by analyzing specimens collected using minimally invasive procedures. Eight miRNAs displayed altered expression in anterior nasal tissues from COVID-19 patients, with miR-142-3p, a negative regulator of interleukin-6 (IL-6) production, the most strongly upregulated. Supervised machine learning analysis revealed that a three-miRNA signature (miR-30c-2-3p, miR-628-3p and miR-93-5p) independently classifies COVID-19 cases with 100 % accuracy. This study further defines the host miRNA response to SARS-CoV-2 infection and identifies candidate biomarkers for improved COVID-19 detection.

Farmers and policy makers pursue management practices that enhance water quality, increase landscape flood resiliency, and mitigate agriculture’s contribution to climate change, all while remaining economically viable. This study presents a holistic assessment of how two practices influence the supply of these ecosystem services—the use of an aerator prior to manure application in haylands, and the stacked use of manure injection, cover crops, and reduced tillage in corn silage production. Field data are contextualized by semi-structured interviews that identify influences on adoption. Causal loop diagrams then illustrate feedbacks from ecosystem services onto decision making. In our study, unseen nutrient pathways are the least understood, but potentially the most important in determining the impact of a practice on ecosystem services supply. Subsurface runoff accounted for 64% to 92% of measured hydrologic phosphorus export. Average soil surface greenhouse gas flux constituted 38% to 73% of all contributions to the equivalent CO2 footprint of practices, sometimes outweighing carbon sequestration. Farmers identified interest in better understanding unseen nutrient pathways, expressed intrinsic stewardship motivations, but highlighted financial considerations as dominating decision making. Our analysis elevates the importance of financial supports for conservation, and the need for comprehensive understandings of agroecosystem performance that include hard-to-measure pathways.

The Cherenkov Telescope Array (CTA) is the next-generation ground-based observatory for very-high-energy gamma-ray astronomy. An innovative 9.7 m aperture, dual-mirror Schwarzschild-Couder Telescope (SCT) design is a candidate design for CTA Medium-Sized Telescopes. A prototype SCT (pSCT) has been constructed at the Fred Lawrence Whipple Observatory in Arizona, USA. Its camera is currently partially instrumented with 1600 pixels covering a field of view of 2.7 degrees square. The small plate scale of the optical system allows densely packed silicon photomultipliers to be used, which combined with high-density trigger and waveform readout electronics enable the high-resolution camera. The camera's electronics are capable of imaging air shower development at a rate of one billion samples per second. We describe the commissioning and performance of the pSCT camera, including trigger and waveform readout performance, calibration, and absolute GPS time stamping. We also present the upgrade to the camera, which is currently underway. The upgrade will fully populate the focal plane, increasing the field of view to 8 degree diameter, and lower the front-end electronics noise, enabling a lower trigger threshold and improved reconstruction and background rejection., Comment: 8 pages, 5 figures, Proceedings of the 37th International Cosmic Ray Conference (ICRC 2021), Berlin, Germany

The emergence of the Sars-CoV-2 virus has posed unique challenges specific to transplantation and donation. For our transplant patients on our waiting lists, they have faced uncertainty, unsure if the pandemic will delay live-saving transplants. In March 2021, Vaccine-Induced Thrombosis and Thrombocytopenia (VITT) and central venous sinus thrombosis was recognized, first in Europe with the Astra-Zeneca ChAdOx01 nCoV-19 vaccine, and then in the United States with the Janssen Covid-19 Ad.26.COV2.S vaccine. Not only did this represent a new risk to describe to our patients and colleagues, but because of the life-threatening nature of this complication, we began receiving offers from donors who had died from VITT (1,2) .

In moderate-seismic regions, cost-effective steel building design solutions such as the R=3 and ordinary concentrically braced frame (OCBF) systems do not consistently provide reliable life...

Hand-holes are present within the body of welded aluminum light poles. They are used to provide access to the electrical wiring for both installation and maintenance purposes. Wind is the main loading on these slender aluminum light poles and acts in a very cyclic way. In the field, localized fatigue cracking has been observed. This includes areas around hand-holes, most of which are reinforced with a cast insert welded to the pole. This study is focused on an alternative design, specifically hand-holes without reinforcement. Nine poles with 18 openings were fatigue tested in four-point bending at various stress ranges. Among the 18 hand-holes tested, 17 failed in one way or another as a result of fatigue cracking. Typically, fatigue cracking would occur at either the 3:00 or 9:00 positions around the hand-hole and then proceed to propagate transversely into the pole before failure. Finite element analysis was used to complement the experimental study. Models were created with varying aspect ratios to see if the hand-hole geometry had an effect on fatigue life.

Few options are available for cytomegalovirus (CMV) treatment in transplant recipients resistant, refractory, or intolerant to approved agents. Letermovir (LET) is approved for prophylaxis in hematopoietic cell transplant (HCT) recipients, but little is known about efficacy in CMV infection. We conducted an observational study to determine the patterns of use and outcome of LET treatment of CMV infection in transplant recipients.Patients who received LET for treatment of CMV infection were identified at 13 transplant centers. Demographic and outcome data were collected.Twenty-seven solid organ and 21 HCT recipients (one dual) from 13 medical centers were included. Forty-five of 47 (94%) were treated with other agents prior to LET, and 57% had a history of prior CMV disease. Seventy-seven percent were intolerant to other antivirals; 32% were started on LET because of resistance concerns. Among 37 patients with viral load 1000 international units (IU)/ml at LET initiation, two experienced 1 log rise in viral load by week 12, and no deaths were attributed to CMV. Ten patients had viral load 1000 IU/ml at LET initiation, and six of 10 (60%) had a CMV viral load 1000 IU/ml at completion of therapy or last known value. LET was discontinued in two patients for an adverse event.Patients treated with LET with viral load 1000 IU/ml had good virologic outcomes. Outcomes were mixed when LET was initiated at higher viral loads. Further studies on combination therapy or alternative LET dosing are needed.

We are firmly in the era of biological big data. Millions of omics datasets are publicly accessible and can be employed to support scientific research or build a holistic view of an organism. Here, we introduce a workflow that converts all public gene expression data for a microbe into a dynamic representation of the organism’s transcriptional regulatory network. This five-step process walks researchers through the mining, processing, curation, analysis, and characterization of all available expression data, using Bacillus subtilis as an example. The resulting reconstruction of the B. subtilis regulatory network can be leveraged to predict new regulons and analyze datasets in the context of all published data. The results are hosted at https://imodulondb.org/, and additional analyses can be performed using the PyModulon Python package. As the number of publicly available datasets increases, this pipeline will be applicable to a wide range of microbial pathogens and cell factories.