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Reckling Peak (RKP) 17085 is a newly classified Antarctic CM chondrite that preserves a complex alteration history characterized by mild aqueous alteration (CM2.7), overprinted by a short‐lived thermal metamorphic event (heating stage III [<750°C]), and affected by low‐grade terrestrial weathering. This meteorite contains abundant Fe‐rich bands within the fine‐grained matrix, composed of micron‐scale Fe‐oxyhydroxide minerals. They are interpreted as "alteration fronts" arising due to the dissolution and transport of Fe (typically <500 μm) before being abruptly deposited. This alteration texture is relatively rare among hydrated carbonaceous chondrites, with only five reported instances to date (Murchison, Murray, Allan Hills 81002, Miller Range 07687, and Northwest Africa 5958). Evidence from RKP 17085 suggests that early aqueous alteration operated as multiple geochemically isolated microenvironments, which moved outwards from local point sources within the matrix. Low permeability fine‐grained rims on chondrules appear to have acted as barriers to fluid flow, controlling the migration of fluid across the parent body. Furthermore, the higher porosity regions within the altered fine‐grained matrix represent either void space generated by the dehydration of hydrated minerals during post‐hydration metamorphism and/or sites of ice accretion (water‐ice or C‐bearing ices) preserved within a mildly altered primitive matrix. [ABSTRACT FROM AUTHOR]

Background Daptomycin stands as a key IV antibiotic in treating MRSA infections. However, patients facing challenges with difficult venous access require alternative administration routes. This study aimed to evaluate the pharmacokinetic (PK) profile and safety of subcutaneous (SC) daptomycin. Patients and methods In a two-period, two-treatment, single-blind crossover Phase I trial (ClinicalTrials.gov NCT04434300), participants with no medical history received daptomycin (10 mg/kg) both IV and SC in a random order, with a minimum 2 week washout period together with matched placebo (NaCl 0.9%). Blood samples collected over 24 h facilitated PK comparison. Monte Carlo simulations assessed the PTA for various dosing regimens. Adverse events were graded according to Common Terminology Criteria for Adverse Events(CTCAE) v5.0. Results Twelve participants (aged 30.9 ± 24.4 years; 9 male,75%) were included. SC daptomycin exhibited delayed (median T max 0.5 h for IV versus 4 h for SC) and lower peak concentration than IV (C max = 132.2 ± 16.0 μg/mL for IV versus 57.3 ± 8.6 μg/mL for SC; P  < 0.001). SC AUC0–24 (937.3 ± 102.5 μg·h/mL) was significantly lower (P  = 0.005) than IV AUC0–24 (1056.3 ± 123.5 μg·h/mL) but was deemed bioequivalent. PTA demonstrated target AUC0–24 attainment for 100% of simulated individuals, for both 8 and 10 mg/kg/24 h SC regimens. Adverse events (AEs) related to SC daptomycin were more frequent than for SC placebo (25 versus 13, P  = 0.016). No serious AEs were reported. Conclusions Single-dose SC daptomycin infusion proved to be safe, exhibiting a bioequivalent AUC0–24 compared with the IV route. The SC route emerges as a potential and effective alternative when IV administration is not possible. [ABSTRACT FROM AUTHOR]

Introduction: Cardiovascular pathologies represent the first cause of death in uremic patients and are among the leading causes of mortality in patients with hereditary angioedema due to C1-inhibitor deficiency (HAE-C1INH). Before 2020, the most common treatment for long-term prophylaxis in HAE-C1INH patients in Italy was attenuated androgen, which may increase cardiovascular risk by multiple mechanisms. Case description: We present a case report of a 56-year-old patient with HAEC1INH type I affected by IgA nephropathy with severe kidney impairment. The patient experienced a first kidney transplant and, after late rejection, underwent a second kidney transplant. Further comorbidities included obesity, hypertensive cardiomyopathy, HCV liver disease, and dyslipidemia. His prophylactic therapy to prevent angioedema attacks had consisted of attenuated androgens for about 40 years. Since 2020, new modern targeted therapy for LTP, particularly lanadelumab, has shown promising results. The majority of patients with attenuated androgens have been successfully switched to lanadelumab, including our patient. Since introducing lanadelumab (300 mg subcutaneously every two weeks; after a six-month attack-free period, the dosing interval of lanadelumab was extended to four weeks), the patient has not experienced any acute HAE attack and did not report any adverse events. Moreover, we observed decreased total cholesterol, C-LDL, and body mass index, reducing the Matsushita et al. score for ten years of cardiovascular risk from 13.2% to 9.3%. Conclusion: lanadelumab is effective and safe in preventing hereditary angioedema attacks, as well as in reducing cardiovascular risk in an immunosuppressed patient with significant comorbidities. The successful outcomes of this case highlight the potential of lanadelumab as a promising prophylactic therapy. [ABSTRACT FROM AUTHOR]

Most research on mass murderers to date has focused on perpetrators of male sex, while research on perpetrators of female sex has been relegated to case reports and series. We aimed to more fully examine the phenomenon of female‐perpetrated mass murder. We analyzed 1715 worldwide incidents of personal‐cause mass murder from 1900 to 2019, identifying 105 (6%) events perpetrated by females. We defined mass murder as any event involving at least three fatalities, not including the perpetrator, using any method. We identified cases of mass murder from English‐language databases of mass murder or murder in print or online. There were no significant differences in age and race between female and male perpetrators. Relative to males, female perpetrators were significantly less likely to employ firearms in their mass murders, using them in less than half of cases, compared to over 70% for males. The prevalence of psychotic signs and symptoms among female mass murderers was more than double that among males (25.7% vs. 12.5%, p < 0.01), while the rate of nonpsychotic psychiatric or neurological conditions was also much greater among female perpetrators (29.5% vs. 17.1%, p < 0.01). Over half of female perpetrators took or attempted to take their own lives. More than three‐quarters of mass murders by females involved at least one family member as a victim. This study underscores sex‐specific differences in the perpetration of mass murder and the need for further research to understand how insights about such dynamics might lead to the development of more effective and informed intervention policies. [ABSTRACT FROM AUTHOR]

Background/Objectives: Anemia during acute inflammation is not well described in the literature. We aimed to study whether patients develop a transient hemoglobin decrease during an acute attack of recurrent pericarditis. Methods: We retrospectively analyzed patients with recurrent pericarditis. The primary endpoint was the difference in hemoglobin levels during an acute attack and in the following remission. As secondary endpoints, we correlated this variation with laboratory and clinical features; we also evaluated the available baseline hemoglobin values. Results: Sixty-two patients, including thirty females (48.4%), with a median age of 39 years, were observed during an acute attack and remission. The attack indexed was the first in 21 patients and the second or the third in 41, with pre-attack hemoglobin levels available for the latter group. Median hemoglobin levels (IQR) were 13.8 (12.8–15.1) g/dL at baseline, 12.0 (11.2–13.4) during attacks and 13.6 (13.1–14.0) during remission (p < 0.001). The median hemoglobin reduction between an acute attack and remission was 1.4 g/dL. Their mean corpuscular volume remained in the normal range. Hb reduction significantly correlated with C-reactive protein (CRP) elevation, neutrophilia and the neutrophil-to-lymphocyte ratio, but not serosal involvement. Only CRP elevation remained associated with the variation of Hb in a multivariate analysis (p = 0.007). Conclusions: This study is a proof of concept: hemoglobin levels may decline rapidly during acute inflammation in correlation with CRP elevation, with transient normocytic anemia, followed by a rapid rebound. In this regard, idiopathic pericarditis may represent a pathogenetic model of this type of anemia. [ABSTRACT FROM AUTHOR]

Modern healthcare increasingly requires interprofessional teams to collaborate both in person and virtually to effectively achieve common goals. To prepare students for interprofessional collaborative practice (CP) universities need evaluation tools that can validly and reliably measure students' CP competencies after online and in-person interprofessional education. The Jefferson Teamwork Observation Guide® (JTOG) is a 360-degree evaluation tool previously validated to measure nationally-defined CP competencies. The psychometrics of the Individual JTOG have been examined in a sample of interprofessional healthcare students after online interprofessional education. The present study examined the psychometric properties of the Individual JTOG in 709 students after in-person interprofessional education using Rasch Modeling and compared results across collaborative settings and student professions. Results indicated that item and person statistics, unidimensionality, scaling performance, and local independence of the Individual JTOG were comparable between online and in-person samples, suggesting it is consistent in its measurement of CP competencies across collaborative settings. Psychometric properties were strong, but ceiling effects were present. Minor deviations were found in the Individual JTOG's unidimensionality between professional groups. The Values and Ethics construct was more strongly separated from others for nursing than other health professions. Recommendations for future research and possible adaptations to the instrument are discussed. [ABSTRACT FROM AUTHOR]

Configurations of support include those that exhibit Support-From-Below (cup "on" table), as well as those involving Mechanical Support (e.g., stamp "on" envelope, coat "on" hook). Mature language users show a "division of labor" in the encoding of support, frequently using basic locative expressions (BE "on" in English) to encode Support-From-Below but lexical verbs (e.g., "stick, hang") to encode cases of Mechanical Support. This suggests that Support-From-Below configurations may best represent the core for the category of support, and could be privileged in supporting early mappings to spatial language. We tested this hypothesis by examining spontaneous productions of children younger than 4 years found in the CHILDES corpora. Children used "on" to encode Support-From-Below more than other types of support configurations. They also showed clear distinctions in how they mapped different verbs (e.g., BE vs. lexical verbs) to Support-From-Below configurations compared to other support configurations. Analysis of parent language suggests that these observed patterns in children's language cannot be fully explained by input, although a role for input is likely for children's encoding of Mechanical Support. Thus, a concept of Support-From-Below may serve as a core representation of support, and hence the privileged spatial representation onto which spatial language for support is mapped.

Abstract Background To compare differences in the probability of COVID-19-related death between native Italians and immigrants hospitalised with COVID-19. Methods This retrospective study of prospectively collected data was conducted at the ASST Fatebenefratelli-Sacco Hospital in Milan, Italy, between 21 February and 31 November 2020. Uni- and multivariable Cox proportional hazard models were used to assess the impact of the patients' origin on the probability of COVID-19-related death. Results The study population consisted of 1,179 COVID-19 patients: 921 Italians (78.1%) and 258 immigrants (21.9%) who came from Latin America (99, 38%), Asia (72, 28%), Africa (50, 19%) and central/eastern Europe (37, 14%). The Italians were significantly older than the immigrants (median age 70 years, interquartile range (IQR) 58–79 vs 51 years, IQR 41–60; p

Machine learning techniques were used to identify highly informative early psychosis self-report items and to validate an early psychosis screener (EPS) against the Structured Interview for Psychosis-risk Syndromes (SIPS). The Prodromal Questionnaire-Brief Version (PQ-B) and 148 additional items were administered to 229 individuals being screened with the SIPS at 7 North American Prodrome Longitudinal Study sites and at Columbia University. Fifty individuals were found to have SIPS scores of 0, 1, or 2, making them clinically low risk (CLR) controls; 144 were classified as clinically high risk (CHR) (SIPS 3-5) and 35 were found to have first episode psychosis (FEP) (SIPS 6). Spectral clustering analysis, performed on 124 of the items, yielded two cohesive item groups, the first mostly related to psychosis and mania, the second mostly related to depression, anxiety, and social and general work/school functioning. Items within each group were sorted according to their usefulness in distinguishing between CLR and CHR individuals using the Minimum Redundancy Maximum Relevance procedure. A receiver operating characteristic area under the curve (AUC) analysis indicated that maximal differentiation of CLR and CHR participants was achieved with a 26-item solution (AUC=0.899±0.001). The EPS-26 outperformed the PQ-B (AUC=0.834±0.001). For screening purposes, the self-report EPS-26 appeared to differentiate individuals who are either CLR or CHR approximately as well as the clinician-administered SIPS. The EPS-26 may prove useful as a self-report screener and may lead to a decrease in the duration of untreated psychosis. A validation of the EPS-26 against actual conversion is underway.

Modern humans have admixed with multiple archaic hominins. Papuans, in particular, owe up to 5% of their genome to Denisovans, a sister group to Neanderthals whose remains have only been identified in Siberia and Tibet. Unfortunately, the biological and evolutionary significance of these introgression events remain poorly understood. Here we investigate the function of both Denisovan and Neanderthal alleles characterised within a set of 56 genomes from Papuan individuals. By comparing the distribution of archaic and non-archaic variants we assess the consequences of archaic admixture across a multitude of different cell types and functional elements. We observe an enrichment of archaic alleles within cis-regulatory elements and transcribed regions of the genome, with Denisovan variants strongly affecting elements active within immune-related cells. We identify 16,048 and 10,032 high-confidence Denisovan and Neanderthal variants that fall within annotated cis-regulatory elements and with the potential to alter the affinity of multiple transcription factors to their cognate DNA motifs, highlighting a likely mechanism by which introgressed DNA can impact phenotypes. Lastly, we experimentally validate these predictions by testing the regulatory potential of five Denisovan variants segregating within Papuan individuals, and find that two are associated with a significant reduction of transcriptional activity in plasmid reporter assays. Together, these data provide support for a widespread contribution of archaic DNA in shaping the present levels of modern human genetic diversity, with different archaic ancestries potentially affecting multiple phenotypic traits within non-Africans.

Objective The aim of this work is to explore patient’ unmet needs of rare and complex rheumatic tissue diseases (rCTDs) patients during pregnancy and its planning by means of the narrative-based medicine (NBM) approach.Methods A panel of nine rCTDs patients’ representatives was identified to codesign a survey aimed at collecting the stories of rCTD patients who had one or more pregnancies/miscarriages. The results of the survey and the stories collected were analysed and discussed with a panel of patients’ representatives to identify unmet needs, challenges and possible strategies to improve the care of rCTD patients.Results 129 replies were collected, and 112 stories were analysed. Several unmet needs in the management of pregnancy in rCTDs were identified, such as fragmentation of care among different centres, lack of education and awareness on rCTD pregnancies among midwifes, obstetricians and gynaecologists. The lack of receiving appropriate information and education on rCTDs pregnancy was also highlighted by patients and their families. The need for a holistic approach and the availability specialised pregnancy clinics with a multidisciplinary organisation as well as the provision of psychological support during all the phases around pregnancy was considered also a priority.Conclusion The adoption of the NBM approach enabled a direct identification of unmet needs, and a list of possible actions was elaborated to improve the care of rCTD patients and their families in future initiatives.

When I teach the history of US policing, I begin our survey by holding up one of the most widely used textbooks on policing, The Police in America by Samuel [...]

Background Recurrent pericarditis is characterized by painful flares and inflammation, which negatively impact health‐related quality of life. RHAPSODY (rilonacept inhibition of interleukin‐1 alpha and beta for recurrent pericarditis: a pivotal symptomatology and outcomes study) evaluated the efficacy and safety of rilonacept (IL‐1α and ‐β cytokine trap) in recurrent pericarditis. A secondary analysis of these data evaluated the patient‐reported outcome questionnaire score change during the trial. Methods and Results Participants completed 5 patient‐reported outcome (PRO) questionnaires assessing pericarditis pain, health‐related quality of life, general health status, sleep impact, and overall symptom severity. PRO score changes during the treatment run‐in period (12 weeks) and the blinded randomized withdrawal period (up to 24 weeks) were evaluated using descriptive statistics and mixed model repeated measures analyses. Participants with PRO data from the run‐in period (n=84) and the randomized withdrawal period (n=61; 30 rilonacept, 31 placebo) were included in analyses. Run‐in baseline PRO scores indicated that pericarditis symptoms during pericarditis recurrence impacted health‐related quality of life. All PRO scores significantly improved (P