Mandatory COVID-19 vaccination for healthcare workers: The experience of chaplains evaluating religious accommodation requests from coworkers.

Mandatory COVID-19 vaccination requirements for healthcare workers in the United States, instituted at the height of the pandemic to protect vulnerable patients and preserve the infrastructure of healthcare, nonetheless met with resistance by some members of the work force. As unprecedented numbers of employees sought religious accommodations, chaplain leaders were recruited by institutional leadership to adjudicate these requests, either alone or as part of a committee. This study reports results of a survey conducted from 6/1/2022 to 7/15/2022 with U.S. healthcare chaplains (n = 76) who were involved in the evaluation of coworker requests for religious exemption to the COVID-19 vaccine anytime during the pandemic until they accessed the survey. Chaplains were recruited online through national chaplaincy and ethics organizations. A mixed methods design facilitates integration of statistically significant associations with chaplains' in-depth reflections on their experience. Surveying the religious experts on the review committee affords a rare look into how the tension between the free exercise of religion in the workplace and the obligation to protect the public played out during the pandemic. The study further addresses a gap in research literature on the experience of chaplains during the pandemic and identifies unique features of moral injury experienced by a subset of healthcare providers. Chaplains largely perceived their involvement as promoting an ethical, informed process of review. Although all chaplains found this role stressful, high levels of meaning were protective against distress. Sources of distress identified included: ethical concern that granting exemptions would lead to the spread of the virus; inconsistencies in the review process; and, repeated exposure to coworkers' misunderstanding and political use of religious teachings. Featuring prominently in comments from chaplains was the difficulty navigating requests in the context of anti-science, anti-vaccine, and politically charged public discourse.

Radiological Screening Methods in Deceased Organ Donation: An Overview of Guidelines Worldwide.

Organ transplantation is performed worldwide, but policies regarding donor imaging are not uniform. An overview of the policies in different regions is missing. This study aims to investigate the various protocols worldwide on imaging in deceased organ donation. An online survey was created to determine the current policies. Competent authorities were approached to fill out the survey based on their current protocols. In total 32 of the 48 countries approached filled out the questionnaire (response rate 67%). In 16% of the countries no abdominal imaging is required prior to procurement. In 50%, abdominal ultrasound (US) is performed to screen the abdomen and in 19% an enhanced abdominal Computed Tomography (CT). In 15% of the countries both an unenhanced abdominal CT scan and abdominal US are performed. In 38% of the countries a chest radiographic (CXR) is performed to screen the thorax, in 28% only a chest CT, and in 34% both are performed. Policies regarding radiologic screening in deceased organ donors show a great variation between different countries. Consensus on which imaging method should be applied is missing. A uniform approach will contribute to quality and safety, justifying (inter)national exchange of organs.

Earth's anomalous middle-age magmatism driven by plate slowdown.

The mid-Proterozoic or "boring billion" exhibited extremely stable environmental conditions, with little change in atmospheric oxygen levels, and mildly oxygenated shallow oceans. A limited number of passive margins with extremely long lifespans are observed from this time, suggesting that subdued tectonic activity-a plate slowdown-was the underlying reason for the environmental stability. However, the Proterozoic also has a unique magmatic and metamorphic record; massif-type anorthosites and anorogenic Rapakivi granites are largely confined to this period and the temperature/pressure (thermobaric ratio) of granulite facies metamorphism peaked at over 1500 °C/GPa during the Mesoproterozoic. Here, we develop a method of calculating plate velocities from the passive margin record, benchmarked against Phanerozoic tectonic velocities. We then extend this approach to geological observations from the Proterozoic, and provide the first quantitative constraints on Proterozoic plate velocities that substantiate the postulated slowdown. Using mantle evolution models, we calculate the consequences of this slowdown for mantle temperatures, magmatic regimes and metamorphic conditions in the crust. We show that higher mantle temperatures in the Proterozoic would have resulted in a larger proportion of intrusive magmatism, with mantle-derived melts emplaced at the Moho or into the lower crust, enabling the production of anorthosites and Rapakivi granites, and giving rise to extreme thermobaric ratios of crustal metamorphism when plate velocities were slowest.

Immediate impact of COVID-19 on transplant activity in the Netherlands.

The rapid emergence of the COVID-19 pandemic is unprecedented and poses an unparalleled obstacle in the sixty-five year history of organ transplantation. Worldwide, the delivery of transplant care is severely challenged by matters concerning - but not limited to - organ procurement, risk of SARS-CoV-2 transmission, screening strategies of donors and recipients, decisions to postpone or proceed with transplantation, the attributable risk of immunosuppression for COVID-19 and entrenched health care resources and capacity. The transplant community is faced with choosing a lesser of two evils: initiating immunosuppression and potentially accepting detrimental outcome when transplant recipients develop COVID-19 versus postponing transplantation and accepting associated waitlist mortality. Notably, prioritization of health care services for COVID-19 care raises concerns about allocation of resources to deliver care for transplant patients who might otherwise have excellent 1-year and 10-year survival rates. Children and young adults with end-stage organ disease in particular seem more disadvantaged by withholding transplantation because of capacity issues than from medical consequences of SARS-CoV-2. This report details the nationwide response of the Dutch transplant community to these issues and the immediate consequences for transplant activity. Worrisome, there was a significant decrease in organ donation numbers affecting all organ transplant services. In addition, there was a detrimental effect on transplantation numbers in children with end-organ failure. Ongoing efforts focus on mitigation of not only primary but also secondary harm of the pandemic and to find right definitions and momentum to restore the transplant programs.

Impact of patatin-like phospholipase domain containing 3 rs738409 G/G genotype on hepatic decompensation and mortality in patients with portal hypertension.

BACKGROUND: The rs738409 C>G p.I148M variant in the patatin-like phospholipase domain containing 3 (PNPLA3)-gene promotes triglyceride accumulation in hepatocytes and hepatic stellate cell activation and has previously been linked to hepatic steatosis/liver fibrosis. AIM: To investigate its impact on hepatic decompensation and (liver-related) mortality in patients who had already developed portal hypertension. Moreover, we assessed its link with hepatic steatosis as evaluated by controlled attenuation parameter. METHODS: We performed a retrospective analysis in prospectively characterised patients with viral hepatitis/fatty liver disease-induced portal hypertension (hepatic venous pressure gradient [HVPG] ≥ 6 mm Hg) diagnosed at the Medical University of Vienna who underwent HVPG measurement (until 2013; n = 372; longitudinal study) or simultaneous HVPG and controlled attenuation parameter measurement (2014-2017; n = 153; cross-sectional study). RESULTS: While survival was similar between PNPLA3-C/C and -C/G patients, we observed substantially increased mortality in PNPLA3-G/G patients. PNPLA3-G/G had no impact on mortality in the subgroup of patients with viral hepatitis; however, we observed a strong independent association between PNPLA3-G/G and hepatic decompensation (adjusted subdistribution hazard ratio [aSHR]: 2.1, 95% confidence interval [95% CI]: 1.1-4; P = 0.024) as well as mortality (overall: aSHR: 2.2, 95% CI: 1.22-3.98; P = 0.009; liver-related: aSHR: 2.2, 95% CI: 1.08-4.46; P = 0.029) in patients with fatty liver disease. Interestingly, even in the subgroup of patients who had already progressed to clinically significant portal hypertension (HVPG ≥ 10 mm Hg), PNPLA3-G/G substantially increased mortality (aSHR: 2.33, 95% CI: 1.27-4.29; P = 0.006). PNPLA3-genotype had no influence on controlled attenuation parameter or the prevalence of values ≥248 dB/m. CONCLUSION: PNPLA3-G/G-genotype seems to double the risks of hepatic decompensation and (liver-related) mortality in patients with portal hypertension due to fatty liver disease. Further studies are warranted to investigate potential underlying pathophysiological mechanisms unrelated to hepatic steatosis.

Subcutaneous diphtheria and tetanus vaccines in children with haemophilia: A pilot study and review of the literature.

INTRODUCTION: Subcutaneous (SQ) vaccination has emerged as standard of care in children with severe bleeding disorders to reduce unnecessary factor exposure and avoid provoking an intramuscular bleed, but little is known about comparative immunogenicity to intramuscular (IM) vaccination. AIM: To confirm immunogenicity of Diphtheria Tetanus acellular Pertussis (DTaP) vaccines administered SQ to individuals <6 years old with haemophilia. METHODS: We performed a retrospective and prospective pilot study of tetanus and diphtheria antibody titres among patients evaluated at our Haemophilia Treatment Centre between 2015-2016. Children with haemophilia who had received three to four doses of DTaP containing vaccine administered SQ were eligible. RESULTS: Eight children met inclusion criteria. The mean age at the time of diphtheria and tetanus antibody testing was 21.1±17.8 months. All children who received SQ diphtheria and tetanus developed a positive antibody titre to both antigens. There was no statistically significant difference in distribution of titre values. The average time between the last dose of vaccine and antibody testing was 6.6±3.9 months among SQ vaccinated subjects. Minor injection site reactions were common with SQ vaccines. CONCLUSION: SQ administration of diphtheria and tetanus vaccination appears to be immunogenic in a pilot study of Haemophilia patients and supports this practice as the standard of care for this population.

Meeting report: international workshop on endocrine disruptors: exposure and potential impact on consumers health.

The French Agency for Food, Environmental and Occupational Health and Safety (Anses) hosted a two-day workshop on Endocrine Disruptors: Exposure and Potential Impact on Consumers Health, bringing together participants from international organizations, academia, research institutes and from German, Swedish, Danish and French governmental agencies. The main objective of the workshop was to share knowledge and experiences on endocrine disruptors (ED) exposure and potential impact on consumers' health, to identify current risk assessment practices and knowledge gaps and issue recommendations on research needs and future collaboration. The following topics were reviewed: (1) Definition of ED, (2) endpoints to be considered for Risk assessment (RA) of ED, (3) non-monotonic dose response curves, (4) studies to be considered for RA (regulatory versus academic studies), (5) point of departure and uncertainty factors, (6) exposure assessment, (7) regulatory issues related to ED. The opinions expressed during this workshop reflect day-to-day experiences from scientists, regulators, researchers, and others from many different countries in the fields of risk assessment, and were regarded by the attendees as an important basis for further discussions. Accordingly, the participants underlined the need for more exchange in the future to share experiences and improve the methodology related to risk assessment for endocrine disrupters.

Peritoneal dialysis tailored to pediatric needs.

Consideration of specific pediatric aspects is essential to achieve adequate peritoneal dialysis (PD) treatment in children. These are first of all the rapid growth, in particular during infancy and puberty, which must be accompanied by a positive calcium balance, and the age dependent changes in body composition. The high total body water content and the high ultrafiltration rates required in anuric infants for adequate nutrition predispose to overshooting convective sodium losses and severe hypotension. Tissue fragility and rapid increases in intraabdominal fat mass predispose to hernia and dialysate leaks. Peritoneal equilibration tests should repeatedly been performed to optimize individual dwell time. Intraperitoneal pressure measurements give an objective measure of intraperitoneal filling, which allow for an optimized dwell volume, that is, increased dialysis efficiency without increasing the risk of hernias, leaks, and retrofiltration. We present the concept of adapted PD, that is, the combination of short dwells with low fill volume to promote ultrafiltration and long dwells with a high fill volume to improve purification within one PD session. The use of PD solutions with low glucose degradation product content is recommended in children, but unfortunately still not feasible in many countries.

[Legionella in drinking water : outcomes of an exchange of ideas on the prevention of waterborne legionellosis]. / Legionellen im Trinkwasserbereich : Ergebnisse eines Fachgespräches zur Prävention trinkwasserbedingter Legionellosen.

Although much is known about Legionella and the illness they cause, the relationship between their concentration in water and the risk of infection remains unclear. A comprehensive body of experience shows that the growth of Legionella in heated water distribution systems can be effectively controlled by following the preventive measures described in the generally acknowledged codes of practice. As orientation to trigger action, a technical action level of 100 colony-forming units in 100 ml water has found wide acceptance as the maximally tolerable concentration of Legionella in drinking water hygiene. However, this value as well as the concept for controlling the growth of Legionella in installations has developed historically. In part, the focus differs between drinking water hygiene and hospital hygiene. Also, there is no harmonized European approach for controlling Legionella. In spite of such differences, there are important international parallels in the assessment of the occurrence of Legionella, in experience with controlling them, and in recommendations for prevention. There is a need particularly for adequate studies to clarify the risk of infection as well as for the publication of existing data and experience showing the efficacy of measures for prevention, disinfection and system upgrading. Such data are necessary to support evidence-based prevention of Legionella infections and to create a better epidemiological data base in Germany. One chance for reaching this target would be to improve practices in diagnosis, reporting and central data evaluation-not only of illness, but including also data on Legionella occurrence. More frequent Legionella testing of pneumonia patients is a prerequisite for this, but particularly also for the rapid identification and removal of the source of infection. Further requirements include better training of planers, plumbers, and operators of drinking water installations about the approach to preventing Legionella contamination of drinking water installations described in standards and guidelines. The further development of practicable concepts for effective Legionella prevention requires good collaboration between public authorities responsible for drinking water and hospital hygiene on the federal and state levels and experts for the prevention of infection, hygiene, and sanitary installations.

Disparity in management of diabetes and coronary heart disease risk factors by sex in DCCT/EDIC.

AIMS: Coronary heart disease (CHD) is a major cause of morbidity and mortality in patients with diabetes. Sex disparity in the treatment of modifiable CHD risk factors in patients with Type 2 diabetes has been reported previously; however, there is little comparable information in Type 1 diabetes. METHODS: We performed a cross-sectional analysis of 1153 subjects with Type 1 diabetes in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort to compare achievement of metabolic and CHD risk factor goals and use of recommended risk factor interventions between the sexes. RESULTS: Women were less likely than men to achieve glycated haemoglobin (HbA1c)<7.0% [adjusted odds ratio (AOR) 0.76, 95% confidence interval (CI) 0.57-0.995] or<8.0% (AOR 0.74, 95% CI 0.58-0.95). Achievement of target lipid levels was not significantly different between the sexes. As in the non-diabetic population, men had higher blood pressure. Women were significantly less likely than men to report using aspirin (AOR 0.77, 0.60-0.99) and angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) (AOR 0.62, 0.49-0.80) and statins (AOR 0.56, 0.43-0.73), even after adjusting for blood pressure and lipid levels, respectively. Reported use of statins was also lower in women than men in the subset that developed a low-density lipoprotein (LDL) cholesterol level>3.4 mmol/l (39% vs. 60%, P<0.05). CONCLUSIONS: In Type 1 diabetes, women report lower frequency than men in the use of interventions that decrease CHD risk. These findings are consistent with reports in the Type 2 diabetic population, showing that risk-reducing measures are underused in women with diabetes.

TLR9 triggering in Burkitt's lymphoma cell lines suppresses the EBV BZLF1 transcription via histone modification.

Endemic Burkitt's lymphoma (BL) is considered to preferentially develop in equatorial Africa because of chronic co-infection with Epstein-Barr virus (EBV) and the malaria pathogen Plasmodium falciparum. The interaction and contribution of both pathogens in the oncogenic process are poorly understood. Earlier, we showed that immune activation with a synthetic Toll-like receptor 9 (TLR9) ligand suppresses the initiation of EBV lytic replication in primary human B cells. In this study we investigate the mechanism involved in the suppression of EBV lytic gene expression in BL cell lines. We show that this suppression is dependent on functional TLR9 and MyD88 signaling but independent of downstream signaling elements, including phosphatidylinositol-3 kinase, mitogen-activated protein kinases and nuclear factor-kappaB. We identified TLR9 triggering resulting in histone modifications to negatively affect the activation of the promoter of EBV's master regulatory lytic gene BZLF1. Finally, we show that P. falciparum hemozoin, a natural TLR9 ligand, suppresses induction of EBV lytic gene expression in a dose-dependent manner. Thus, we provide evidence for a possible interaction between P. falciparum and EBV at the B-cell level and the mechanism involved in suppressing lytic and thereby reinforcing latent EBV that has unique oncogenic potential.

The bicuspid aortic valve: an integrated phenotypic classification of leaflet morphology and aortic root shape.

OBJECTIVE: To establish a classification of bicuspid aortic valve (BAV) that includes both leaflet morphology and aortic shape. SETTING: Two academic medical centres of the University of Washington, Seattle. PATIENTS: 191 adult patients with BAV. INTERVENTIONS: Review of clinical data and transthoracic echocardiograms. MAIN OUTCOME MEASURES: Assessment of leaflet morphology; valve function; aortic shape and dimensions. RESULTS: We identified three morphologies: type 1, fusion of right and left coronary cusp (n = 152); type 2, right and non-coronary fusion (n = 39); and type 3, left and non-coronary fusion (n = 1). Comparing type 1 and 2 BAV, there were no significant differences in age, height, weight, blood pressure or aortic valve function. Type 1 was more common in men (69 vs 45%). The aortic sinuses were larger in type 1, while type 2 had larger arch dimensions. Myxomatous mitral valves were more common in type 2 BAV (13% vs 2.6%, p<0.05). Three aortic shapes were defined: normal (N), sinus effacement (E), and ascending dilatation (A). Comparing type 1 to type 2 BAV, shape N was more common in type 1 (60% vs 32%), and type A was more common in type 2 (35% vs 54%,); type E was rare (p<0.01 across all groups). CONCLUSION: A comprehensive BAV phenotype includes aortic shape. Type 1 BAV is associated with male gender and normal aortic shape but a larger sinus diameter. Type 2 leaflet morphology is associated with ascending aorta dilatation , larger arch dimensions and higher prevalence of myxomatous mitral valve disease.

[Drinking water analysis for Legionella. Suggestions for sampling, laboratory analysis and assessment]. / Legionellenuntersuchung bei der Trinkwasseranalyse : Hinweise zur Probenahme, Durchführung im Labor und Bewertung.

Drinking water analysis for Legionella from building installations is done quite frequently. Some questions arise from experience with this analysis. They will be discussed to allow uniform and comparable execution. Application of DIN EN ISO 19458 will lead to changes in the sampling procedure. This may make changes necessary even in current sampling and assessment programs. Concerning laboratory investigation, quality control of membrane filters and media turned out to be crucial. The assessment of quantitative results requires knowledge of the drinking water distribution system and of other facts that may be relevant for hygiene. Therefore, the assessment ought to be conducted by somebody with the respective knowledge.

Analysis of tumor-associated stromal cells using SCID GFP transgenic mice: contribution of local and bone marrow-derived host cells.

The green fluorescence protein (GFP) from the UBI-GFP/BL6 transgenic line was bred into C57BL/6J-scid and C.B-17-scid mice for investigating host-tumor cell interactions. These mice express high levels of GFP under the control of the ubiquitin promoter in virtually all cells examined. In tumor tissue generated by implanting tumor cells in the GFP transgenic SCID mice, the tumor cells and tumor-associated murine host cells were clearly distinguished by GFP expression. A population of cells expressing the endothelial cell marker VEGFR-2/Flk-1, and the progenitor markers c-Kit and Sca-1, were incorporated into tumor tissue. The majority of the Flk-1-positive cells were hematopoietic-derived cells that coexpressed CD45. To investigate the contribution of bone marrow-derived cells to the formation of tumor vessels and stroma, tumor cells were implanted in nontransgenic SCID mice that received a bone marrow transplant from GFP-expressing SCID mice. Although GFP-positive cells were readily detected by histology in tumors taken from bone marrow transplanted animals, they were spatially isolated and lacked organization. In contrast, if tumors were implanted in nontransgenic SCID mice adjacent to a patch of transplanted GFP-expressing skin, these tumors recruited GFP-positive cells that organized into tumor vessels. The results demonstrate that hematopoietic-derived cells, including Flk-1+/CD45+ cells, readily colonized the tumor stroma but were minimally incorporated in the tumor vasculature. The majority of the tumor vessels were instead recruited from tissue adjacent to the tumor. The expression of Flk-1 on nonendothelial, tumor-associated host cells raises the possibility that VEGF antagonists, such as Avastin, could inhibit tumor growth by a mechanism involving hematopoietic-derived CD45+/Flk-1+ cells, in addition to direct suppression of endothelial cell function.

Validity of wave-front reconstruction and propagation of ultrabroadband pulses measured with a Hartmann-Shack sensor.

Wave-front reconstruction for ultrabroadband laser pulses is verified by use of a Hartmann-Shack sensor. We estimate the accuracy of numerical wave-front propagation by comparing numerical with experimental results and verify that wave fronts of ultrabroadband laser pulses from a hollow fiber can be propagated correctly by a single polychromatic wave-front measurement to a place where detection is not practicable, e.g., inside a vacuum chamber or laser focus.

Characterization of the solubility of a poorly soluble hydroxylated metabolite in human urine and its implications for potential renal toxicity.

The solubility, in human urine, of the major hydroxylated metabolite (M1) of an experimental cognition enhancer was characterized through a series of in vitro experiments in an effort to estimate the probability of crystalluria occurring following oral administration of the parent compound. The aim of these experiments was to determine if a safety margin existed between clinically observed urine concentrations and the solubility of M1. The mean urine concentrations of M1 in young and elderly subjects following oral administration of the parent compound at the highest doses tested, were 4865 +/- 2368 ng/mL and 2764 +/- 791 ng/mL, respectively. In vitro solubility experiments with M1 were conducted in drug-free human urine (37 degrees C) from four male and four female healthy subjects under conditions of high and low urine osmolality. Mean concentrations (n = 16) of M1 in human urine to which solid M1 was added, were 3656 +/- 621 ng/mL, 4678 +/- 1169 ng/mL and 5378 +/- 2474 ng/mL after stirring for 24, 48 and 72 h, respectively, indicating that the ex vivo mean solubility of M1 in human urine is no greater then approximately 5 microg/mL. Addition of solid M1 to urine from human subjects dosed with the parent compound resulted in mean urine M1 concentrations 23.5% greater than those observed in vivo. The results from both experiments indicated a significant overlap between urine concentrations of M1 in vivo following the highest oral administration of the parent drug and M1 solubility measured in vitro, suggesting a high potential for in vivo saturation of urine with M1 with subsequent precipitation, crystalluria, and nephrotoxicity. Consequently, the results of these studies have placed restrictions on the dose that could be administered during clinical development of this compound.

Empirical fear profiles among American youth.

Fears among children can range from relatively innocuous fears of simple objects to significant phobias that affect youths' everyday functioning in the home, school, or community environments. This study investigated empirically derived fear profiles among American youth ages 7-19 (N=556). Based upon youths' scores on the 5 factors of the Fear Survey Schedule for Children-II (FSSC-II; Burnham & Gullone (Behav Res Ther, 35, 1997)), multistage Euclidean grouping was applied and produced 5 replicable fear cluster profiles with unique contours. Logistic regression odds ratios revealed specific associations of profile group membership with demographic characteristics such as child age, sex, and ethnicity.

The thought disorder questionnaire.

OBJECTIVE: To describe the development of the Thought Disorder Questionnaire (TDQ), including data on reliability and validity, and to explain the questionnaire's feasibility and diagnostic accuracy. METHODS: The TDQ has 6 scales, each with 10 items (on a scale from 0 [for never] to 4 [for always]). The 6 scales measure content of thought, control of thought, orientation, perception, fantasy, and symptoms. RESULTS: The TDQ is a reliable 60-item, self-report questionnaire that measures the quantity and quality of disordered thinking in patients with mental disorders. It has established reliability and validity. CONCLUSION: The TDQ's clinical and research utility remains to be determined.