Purpose: to compare, in a real-world scenario, the effects of different levels of technology on attention, memory, electrophysiological response, and self-perceived benefit of new users of hearing-aids in a developing country such as Brazil. Method: A pragmatic parallel-group, single-blinded, and randomized pilot clinical trial was conducted. Patients were divided into 3 groups according to hearing aid technology: (A) advanced technology; (B) basic technology; and (C) placebo. Participants were ≥ 60 years old, had moderate sensorineural hearing loss, and had never been exposed to hearing aid before. Prior to data collection, patients were electronically randomized to receive unique identity numbers. Patient numbers were placed in opaque envelopes until the day of the first visit at which hearing aids were fitted with appropriate amplification settings. Attention, memory, and latency of auditory evoked potentials of patients were assessed while using the hearing aids at baseline and then after 12 weeks of use. The primary outcome was any improvement in scores on neuropsychological tests and/or shortening of latency in the auditory-evoked potentials. Results: A total of 22 individuals were assessed (A=8, B=6, and C=8). Participants had a mean age of 80.4 (±6.1) years, were predominantly female (63.63%), and were poorly educated (3.8±1.6 years). Comparison of groups AXC and of BXC revealed differences in NEUPSILIN scores (Brazilian instrument) for reverse counting (p=0.002, 95%CI 5.9;20.55) and recognition (p=0.013, 95%CI -6.1;-0.88). No difference between groups A and B were found. Responses on the International Outcome Inventory for Hearing Aids (IOI-HA) differed for the benefit (p<0.001), satisfaction (p=0.007), participation restriction (p=0.012) and quality of life (p=0.037). Conclusion: The level of technology of the devices had no impact on the general satisfaction of new users of hearing-aids and appeared to have no differential effect on memory or attention after 12 weeks of use of the sound amplification products.

Background: Complex cardiac operations may have better outcomes when performed by mid-career surgeons compared with surgeons in early or late stages of their career. However, it is unknown how cardiac case complexities are distributed among surgeons of different experience levels. Methods: We performed a cross-sectional study using New York (NY) and California (CA) statewide surgeon-level coronary artery bypass grafting (CABG) outcome data, including 336 cardiac surgeons who performed 43,604 CABGs. Surgeon-level data including observed mortality rate (OMR) and expected mortality rates (EMR) was collected from 2014-2016 in NY and 2015-2016 in CA. Surgeons’ number of years-in-practice was determined by searching for each surgeon’s training history on online registries. Loess and linear regression models were then used to characterize the relationship between surgeon EMR and surgeon years-in-practice. Results: The median number of surgeon years-in-practice was 20 (interquartile range [IQR] 11-28) with median case volume 103 (IQR 42,171). The median surgeon observed to expected mortality (O:E) ratio was 0.87 (IQR 0.19-1.4). Linear regression relating EMR to years in practice showed that EMR was similar across years in practice. Linear regression relating surgeon isolated CABG O:E ratio to years in practice also showed similar outcomes across years in practice. Conclusion: There is a relatively equal distribution of high and low risk CABG cases among surgeons of differing experience levels. This equal distribution of high and low risk cases does not reflect a triaging of more complex cases to more experienced cardiac surgeons, which prior research shows may optimize patient outcomes.

Adenosine triphosphate (ATP) hydrolysis is a well-known biological reaction which plays an important role in many biological processes. In this study, we have modelled the non-enzymatic hydrolysis of ATP in the gas-phase and the aqueous-phase by performing ab initio molecular dynamics simulations combined with an enhanced sampling technique. In the gas-phase, we studied hydrolysis of fully protonated ATP molecule and in the aqueous-phase, we studied hydrolysis of ATP coordinated with: a) two H+ ions (H-ATP), b) Mg2+ (Mg-ATP) and c) Ca2+ (Ca-ATP). We show that gas-phase ATP hydrolysis follows a two-step dissociative mechanism via a highly stable metaphosphate intermediate. The Adenine group of the ATP molecule plays a crucial role of a general base; temporarily accepting protons and, thus helping in the elimination-addition process. In the aqueous-phase hydrolysis of ATP, we find that the cage of solvent molecules increases the stability of the terminal phospho-anhydride bond through a well-known cage-effect. Further, we find that the aqueous-phase hydrolysis happens with the help of nearby water molecules, which assumes the role of a base assisting in proton diffusion through Grotthuss mechanism. We obtained much lower free-energy barriers for the aqueous-phase hydrolysis of ATP coordinated with divalent ions (Mg2+ and Ca2+) compared to hydrolysis of ATP coordinated with only H+ ions, suggesting a clear catalytic effect of the divalent ions. We find a single-step dissociative-type mechanism for Mg-ATP, while we find a SN-2-type concerted hydrolysis pathway for Ca-ATP.

Wheezing is a common outcome of preterm birth. This article will review the mechanisms, epidemiology, and treatment of wheezing in preterm children with and without a history of bronchopulmonary dysplasia

A document by Peter Braude. Click on the document to view its contents.

Rationale, aims and objectives: People living with dementia admitted to hospitals are more likely to experience poorer outcomes than people without dementia. Caregivers play an important role in managing medications across transitions of care. This qualitative study explores the experiences and perspectives of caregivers about the medication management guidance provided at hospital discharge. Methods: A qualitative approach using semi-structured, telephone interviews was conducted with 31 caregivers of people with dementia across Australia. Purposive sampling was used to ensure maximum variation of diverse experiences and perspectives. Results: Caregivers’ experiences of medication guidance for people with dementia at discharge were described in three themes including: a) inadequate information about medication management at discharge; b) limited caregiver engagement in medication management decisions; and c) difficulties ensuring medication supply post discharge. Most participants indicated they would like to be included in discussions at discharge. However, participation was influenced by caregivers being overwhelmed by discharge processes; proactively seeking information on medication-related harm; and belief in advocacy as part of their caregiver role. Caregivers reported they would like to receive a tailored medication list for people with dementia which included information on medications that may impact on the patient’s cognition, and for hospital staff to communicate with both the community pharmacist and primary care physician, to improve co-ordination post transition. Discussion: In our study of caregivers of people with dementia, we identified key recommendations that could be tested to facilitate regular participation of people living with dementia and their caregiver around medication guidance at discharge.

Evaluation of population-based COVID-19 control measures informs strategies to quell the current pandemic and reduce the impact of those yet to come. Effective COVID-19 control measures may simultaneously reduce the incidence of other acute respiratory infections (ARIs) due to shared transmission modalities. To assess the impact of stay-at-home orders and other physical distancing measures on the prevalence of ARI-related symptoms, we compared symptoms reported by prospective college cohorts enrolled during two consecutive academic years. ARI-related symptoms declined following campus closure and implementation of stay-at-home orders, demonstrating the impact of population-based physical distancing measures on control of a broad range of respiratory infections.

Histoplasmosis occurs primarily in the lungs but can disseminate in immunocompromised patients. Serology can be negative in patients with local infection, making the diagnosis challenging. Definite diagnosis is by microscopic examination of the tissue sample. We report a rare case of Histoplasma stomatitis whose lesions manifested after initiating antiretroviral therapy.

Burkitt lymphoma is a rapidly progressive disease which requires imaging, biopsy, prompt diagnosis and early aggressive chemotherapeutic treatment. We discuss a 7-year-old girl presenting with a persistent and painful unilateral swelling of the jaw. Lymphomas typically manifest as poor defined osteolytic lesions radiographically, as is presented in this case.

Background: Respiratory syncytial virus (RSV) bronchiolitis is the most common lower respiratory tract disorder causing hospitalization in infants. Palivizumab has shifted the profile of the hospitalized population away from premature infants and towards those with chronic morbidities who are not eligible for prophylaxis. Aim: To characterize RSV bronchiolitis hospitalizations in infants with chronic diseases, compared to otherwise healthy infants. Methods: A four consecutive RSV season retrospective analysis of patients younger than two years admitted with bronchiolitis. Background demographic and clinical data, including vital sign measurements, laboratory tests, and pediatric intensive care unit (PICU) admissions during hospitalization, were analyzed. Results: Of 1124 hospitalizations due to RSV bronchiolitis, 244 (22%) were in infants with chronic diseases. Although 20/1124 qualified for RSV prophylaxis, only 8 had been vaccinated. Compared to otherwise healthy infants, children with chronic diseases had longer hospitalizations, median 4 days (IQR 4-7) vs 3 days (2-5), p<0.001; and higher PICU and readmission rates (9% vs 4.5%, p=0.007 and 3% vs 1%, p=0.055, respectively). Children with Down’s syndrome comprised 2% of all hospitalizations, but 8% of PICU admissions; their median length of hospitalization was 11 days. Respiratory tract malformations were present in 2% of hospitalizations, and comprised 4% of PICU admissions. Conclusion: Infants with chronic diseases admitted with RSV bronchiolitis are prone to longer hospitalization and PICU admission. Children with Down’s syndrome and respiratory tract malformations may benefit from RSV prophylaxis.

Comment on: The use of anakinra in the treatment of secondary hemophagocytic lymphohistiocytosis1Paige Vicenzi, OMS-IV, 2Zahra Jiwani, DO, 3Ricardo Guirola, MD,1,4Tyler Hamby, PhD, 5Anish Ray, MD1Texas College of Osteopathic Medicine, University of North Texas Health Science Center2Department of Pediatrics, Children’s Hospital of Michigan3Department of Pediatric Rheumatology, Cook Children’s Health Care System4Department of Research Operations, Cook Children’s Health Care System5Department of Pediatric Hematology/Oncology, Cook Children’s Health Care SystemCorresponding Author:Anish Ray, MD1500 Cooper St., 5th floor,Fort Worth, TX 76104Phone: [email protected] Count: 497Number of Tables: 0Number of Figures: 1Running Title: Anakinra in Secondary HLHKeywords: hemophagocytic lymphohistiocytosis, anakinra, pediatricThe authors have no financial support or conflicts of interest.Hemophagocytic lymphohistiocytosis (HLH) is a rare yet potentially fatal systemic disease arising from uncontrolled activation of the immune system. According to the Histiocyte Society’s 2004 guidelines, patients must meet five of eight criteria to be diagnosed with HLH [1]. HLH may be classified into primary and secondary. Primary, or familial, HLH is attributed to underlying defects in genes that control natural killer (NK) and cytotoxic T-lymphocyte (CTL) cell degranulation. Secondary HLH, in contrast, may occur in the context of triggers, such as malignancy, rheumatologic disease, or infection. Systemic-onset juvenile idiopathic arthritis (SoJIA) is a well-recognized trigger of HLH and both share overlapping features (e.g. fever and elevated ferritin). Management of SoJIA includes the immunomodulator Anakinra, an interleukin 1 (IL-1) receptor antagonist hypothesized to dampen an overactive immune system. Three patients treated for HLH with concomitant SoJIA diagnosis at Cook Children’s Medical Center between 2014 and 2019 are described below in order to examine the role of immunomodulators in their clinical course and outcome.Three Hispanic patients (aged 8-15) presented with a constellation of systemic symptoms, including fever, generalized rash, fatigue, and weight loss. Upon fulfilment of necessary criteria and subsequent diagnosis of HLH, they were treated accordingly with HLH-2004 protocol. Case 3, whose HLH was suspected to be secondary to Epstein-Barr Virus (EBV) infection, rapidly responded to treatment and, therefore, briefly discontinued Etoposide; however, she tolerated this poorly and resumed treatment after a six-week hiatus with the addition of weekly Rituximab to mitigate rising EBV titers. All patients achieved remission.Past medical history for case 3 included autoimmune disorders such as celiac disease, type 1 diabetes and suspected idiopathic juvenile arthritis for which she did not require ongoing care prior to presenting with features of secondary HLH. Cases 1 and 2 were diagnosed with SoJIA following their HLH diagnosis. Cases 1 and 3 relapsed with HLH within months of their initial encounter. Due to their concurrent diagnosis of SoJIA, both received daily Anakinra. Case 3 experienced rapid resolution of symptoms. In contrast, Case 1 had unsatisfactory response of musculoskeletal manifestations prompting switch from Anakinra to weekly Tocilizumab—another biologic that antagonizes IL-6 receptor—with favorable response. Case 2 was started on daily Anakinra immediately following his diagnosis of SoJIA and has yet to relapse. In summary, all cases have yet to experience an additional relapse following introduction of Anakinra or Tocilizumab. Figure 1 provides the treatment timelines for Cases 1-3 who had 5.37, 2.87, and 4.62 years of follow up, respectively.Though traditional therapy for HLH includes intensive courses of etoposide and corticosteroids with substantial risk for morbidity and mortality, biologics represent a newer class of medications highly effective in treating diseases with inflammatory or immune-mediated components [2]. In a reimaging of the HLH treatment algorithm, a recent study proposes Anakinra as initial treatment with sequential escalation of immunosuppression to mitigate adverse effects [3]. This case series reinforces that immunomodulators, such as Anakinra, are safe and promising treatment options in pediatric patients with secondary HLH.

Background: Ablation index (AI) linearly correlates with lesion depth and may yield better therapeutic performance in pulmonary vein isolation (PVI) when tailored to a patient’s wall thickness (WT) in the left atrium (LA). Methods and results: (First study) In paroxysmal atrial fibrillation patients (PAF, n=20), the average LA WT (mm) in each anatomical segment for PVI was measured by intra-cardiac echocardiography (ICE) placed in the LA; the optimal AI for creating one-millimeter transmural lesion (AI/mm) was calculated. (Second study) PAF (n=80) patients were randomly assigned either to a force-time integral protocol (FTI, 400 gram·second, n=40) or a tailored-AI protocol (TAI, n=40). In TAI, the LA WT in each segment was individually measured by ICE before starting ablation; a target AI was adjusted according to the individual WT in each segment (AI/mm×WT). The acute procedure outcomes and the 1-year AF recurrence rate were compared between FTI and TAI. TAI had higher success rate of first-pass isolation and had lower incidence of residual PV-potentials/conduction gaps after a circular ablation than FTI (88% vs. 65%, 15 vs. 45%, respectively). The procedure time to complete PVI decreased in TAI compared to FTI (52 vs. 83 minutes), being attributed to the increased radiofrequency power and the decreased radiofrequency application time in each point in TAI. TAI had lower 1-year AF recurrence rate than FTI. Conclusion: WT-based AI-adjustment increased acute procedure success, decreased time for PVI, and reduced 1-year AF recurrence rate. Understanding the precise ablation target would improve the efficacy of PVI.

1. Bat abundance, diversity and behaviour can be monitored by capturing bats for identification and measurement in the hand, but this has several disadvantages. These include disturbance to the bats, which limits the frequency with which captures can be made at an individual capture site, and potentially alters the behaviours being studied. 2. Passive recording and automated analysis and identification of bat calls offers an alternative, non-invasive approach to monitoring bats. In this study, we examine the effectiveness of acoustic monitoring in comparison with capture-based monitoring of seasonal swarming behaviour among several species of Myotis bats in southern Britain. 3. We show that both approaches have advantages and disadvantages for different tasks, but can be viewed as complementary methods for addressing different types of research questions. 4. We applied these complementary approaches, together with observations from infra-red video monitoring, to describe seasonal, overnight and species-specific variation in swarming behaviour in a multi-species community of Myotis bats. 5. In our study of swarming behaviour, capture and examination of bats in the hand was necessary for measuring sex ratios, reproductive status, and even for confirmation of species identification for some difficult to separate taxa. Capture is also an essential aspect of tagging bats for individual identification and tracking studies. 6. Passive acoustic monitoring is a valuable non-invasive method for continuous monitoring of within-night, seasonal and between-year variation in the abundance of bat calls. These can be used as an index of variation in relative abundance within -- but not between -- bat species.

Biological invasions are accelerating, and invasive species can have large economic impacts as well as severe consequences for biodiversity. During invasions, species can interact, potentially resulting in hybridization. Here, we examined two Cakile species, C. edentula and C. maritima (Brassicaceae), that co-occur and may hybridize during range expansion in separate regions of the globe. Cakile edentula invaded each location first, while C. maritima established later, apparently replacing the former. We assessed the evidence for hybridization in western North America and Australia, where both species have been introduced, and identified source populations with 4561 SNPs using Genotype-by-Sequencing. Our results indicate that the C. edentula in Australia originated from one region of eastern North America while in western North America it is likely from multiple sources. The C. maritima in Australia were derived from at least two different parts of Europe while the introduction in western North America is from one. Although morphological evidence of hybridization is generally limited to mixed species populations in Australia and virtually absent elsewhere, our genetic analysis revealed relatively high levels of hybridization in Australia (58% hybrids) and supported the presence of hybrids in western North America (16%) and New Zealand. Hybrids might be commonly overlooked in invaders, as identification based solely on morphological traits may represent only the tip of the iceberg. Our study reveals a repeated pattern of invasion, hybridization and apparent replacement of one species by another, which offers an opportunity to investigate the role of hybridization and introgression during invasion.

Skin is the largest mammalian organ and the first defensive barrier against the external environment. The skin and fur of mammals can host a wide variety of ectoparasites, many of which are phylogenetically diverse, specialized, and specifically adapted to their hosts. Among hematophagous dipteran parasites, volatile organic compounds (VOCs) are known to serve as important attractants, leading parasites to compatible sources of blood meals. VOCs have been hypothesized to be mediated by host-associated bacteria, which may thereby indirectly influence parasitism. Host-associated bacteria may also influence parasitism directly, as has been observed in interactions between animal gut microbiota and malarial parasites. Hypotheses relating bacterial symbionts and eukaryotic parasitism have rarely been tested among humans and domestic animals, and have to our knowledge never been tested in wild vertebrates. In this study, we use Afrotropical bats, hematophagous ectoparasitic bat flies, and haemosporidian (malarial) parasites vectored by bat flies as a model to test the hypothesis that the vertebrate host microbiome is linked to parasitism in a wild system. We identify significant correlations between bacterial community composition of the skin and dipteran ectoparasite prevalence across four major bat lineages, as well as striking differences in skin microbial network characteristics between ectoparasitized and non-ectoparasitized bats. We also identify links between the oral microbiome and presence of malarial parasites among miniopterid bats. Our results support the hypothesis that microbial symbionts may serve as indirect mediators of parasitism among eukaryotic hosts and parasites.

Aims: To evaluate the diagnostic yield of investigations performed on patients with a history of urinary tract infections (UTI). Methods: A retrospective review was conducted on patients who underwent cystoscopy and imaging for a history of UTI between 2014-2019 in a single UK teaching hospital. Data was collected on demographics, cystoscopy and radiological findings requiring further management. The cohort was stratified by age, gender, and a confirmed history of recurrent UTI (rUTI). The subsequent algorithm was re-tested in a second cohort to validate its use. Results: 700 patients were included in the primary analysis, 427 female and 273 males. 331 meet the criteria of rUTI. The median age was 64y(18-97). Imaging abnormalities were equally frequent in males 6.3%(15/241) and females 8%(30/380) and the majority noted in patients aged ≥55y, 30/45(66.7%). Amongst those who did not meet the definition of rUTI, abnormal imaging was identified in 5-7% regardless of age group and gender. Cystoscopy abnormalities (n=24) were twice more likely in males, 5.5%(15/273) than females, 2%(9/427). 88%(21/24) were identified in patients ≥55y. There were no positive findings in women <55y. Applying baseline imaging but confining cystoscopy to those aged ≥55y and men with a confirmed history of rUTI would have saved 44% of procedures, missed no abnormalities with an overall diagnosis detection rate of 9.8%(69/700). This algorithm was validated in a separate cohort of 63 patients; applying it would have saved 46%(29/63) of cystoscopies with a positive diagnostic rate of 9.5% and no missed findings. Conclusion: To our knowledge this is one of the largest studies reporting the outcomes of investigations for UTI and rUTI. Our result suggests that imaging is a useful baseline assessment, but cystoscopy should be limited to specific subgroups. We propose and validate a simple decision algorithm to manage investigations for referrals for UTI in secondary care.

Genomic-based epidemiology can provide insight into the origins and spread of herbicide resistance mechanisms in weeds. We used kochia (Bassia scoparia) populations resistant to the herbicide glyphosate from across western North America to test the alternative hypotheses that 1) a single EPSPS gene duplication event occurred initially in the Central Great Plains and then subsequently spread to all other geographical areas now exhibiting glyphosate-resistant kochia populations or that 2) gene duplication occurred multiple times in independent events in a case of parallel evolution. We used qPCR markers previously developed for measuring the various units of the EPSPS tandem duplication to investigate whether all glyphosate-resistant plants had the same EPSPS repeat structure. We also investigated population structure using simple sequence repeat (SSR) markers to determine the relatedness of kochia populations from across the Central Great Plains, Northern Plains, and the Pacific Northwest. We identified three distinct EPSPS-duplication haplotypes that had geographic associations with the Central Great Plains, Northern Plains, and Pacific Northwest. Population structure revealed a group of populations around the first reported occurrence of glyphosate resistance in the Central Great Plains, a separate group of Pacific Northwest populations, and some relatedness of populations from geographically isolated areas. The results support at least three independent origins of glyphosate resistance in kochia, followed by substantial and mostly geographically localized gene flow to spread the resistance alleles into diverse genetic backgrounds.

Snow is Earth’s most climatically sensitive land cover type. Air temperature and moisture availability are first-order controls on snowfall. Maximum snowfall occurs at temperatures very near 0°C, so even a slight increase in temperature will shift a snowy winter to one with midseason rainfall and melt events. Traditional snow metrics are not able to adequately capture the changing nature of snow cover. For example, April 1 snow water equivalent (SWE, the amount of water represented by the snowpack) is used as a streamflow predictor. Still, it cannot express the effects of midwinter melt events, now expected in warming snow climates. The multiple impacts of a changing snowpack require a suite of climate indicators derived from readily measured or modelled data that serve as proxies for relevant snow-related and climate-driven processes. Such indicators need to be simple enough to “tell the story” of snowpack changes over space and time, but not overly simplistic as to be conflated with other variables or, conversely, overly complicated in their interpretation. This paper describes a targeted set of spatially explicit, multi-temporal snow metrics for multiple sectors, stakeholders, and scientists. They include metrics based on satellite data from NASA’s Moderate Resolution Imaging Spectroradiometer, meteorological observations and snow data from ground-based stations, and climate model output. We describe and provide examples for Snow Cover Frequency (SCF), Snow Disappearance Date (SDD), snowstorm temperature (ST), At-Risk Snow (ARS), and Frequency of a Warm Winter (FWW).