The construction of national and religious identities amongst Australian Isma’ili Muslims

Australian civic society has become increasingly multicultural and diverse. Nevertheless, in the current political climate, Australian Muslims may feel as though they live under a microscope of scrutiny with their sense of affiliation and allegiance questioned. The narrative regarding Muslims in Australia has largely focused on Sunnis and ethnic Arabs. This qualitative study examines the Australian Shi’a Isma’ili Muslim community – a minority within a minority – and how attachment to supraordinate identity markers of ‘Muslim’ and ‘Australian’ influence their identity construction. It utilised semi-structured interviews with 16 first- and second-generation Isma’ili Muslims to examine the intersection of national, religious, and cultural identities via the lens of Identity Process Theory (IPT). Religious identity was important to respondents, who spoke of how their ‘double minority’ status distinguished them vis-à-vis the broader Muslim community in Australia and Australian society overall. Nevertheless, respondents noted a strong sense of instrumental attachment to Australia which enabled them to develop a distinct niche of Isma’ili Muslim identity unique to the Australian landscape

B-type natriuretic peptide levels predict outcomes in infants undergoing cardiac surgery in a lesion-dependent fashion

ObjectiveB-type natriuretic peptide is used in the diagnosis, risk stratification, and management of adult patients with cardiac disease. However, its use in infants with congenital heart disease has been limited, particularly in the perioperative period. Our objective was to determine the alterations in perioperative B-type natriuretic peptide levels and their predictive value on postoperative outcomes, in infants undergoing congenital heart surgery.MethodsWe prospectively enrolled 115 patients: 24 with univentricular heart disease undergoing a modified Norwood procedure, 11 with d-transposition of the great arteries, 55 with hemodynamically important left-to-right shunt, and 25 with tetralogy of Fallot undergoing primary repair. Clinical data and B-type natriuretic peptide samples were collected before and 2, 12, and 24 hours after cardiopulmonary bypass. Univariate analysis and multivariate linear regression analysis were performed.ResultsThe perioperative B-type natriuretic peptide levels were lesion specific. Patients with d-transposition of the great arteries and univentricular heart disease had high preoperative B-type natriuretic peptide levels that decreased postoperatively, and those with hemodynamically important left-to-right shunts and tetralogy of Fallot had lower preoperative levels that increased during the first 12 hours postoperatively. The patients with univentricular heart disease with an adverse outcome had a significantly greater 24-hour B-type natriuretic peptide level than those without (P < .05). Those with hemodynamically important left to right shunts and an adverse outcome had a greater 12-hour B-type natriuretic peptide level than those without (P < .05). A 12-hour postoperative/preoperative ratio greater than 45 was 100% sensitive and 82% specific for an adverse outcome in the patients with tetralogy of Fallot.ConclusionsThe perioperative changes in B-type natriuretic peptide levels and their ability to predict outcomes are lesion-specific. Characterization of these changes might be useful in caring for infants after congenital heart surgery

Endostatin, an inhibitor of angiogenesis, decreases after bidirectional superior cavopulmonary anastamosis.

Pulmonary arteriovenous malformations (PAVMs) are a common source of morbidity after bidirectional superior cavopulmonary anastomosis (Glenn). The diversion of hepatic venous effluent away from the pulmonary circulation after Glenn appears to play a significant role in the pathogenesis of PAVMs. Although the liver is known to produce factors that regulate vascular development, specific hepatic inhibitors of angiogenesis have not been described in the post-Glenn population. Endostatin, produced from its precursor collagen XVIII, is a potent inhibitor of angiogenesis produced by the liver. This study aimed to investigate the hypothesis that endostatin levels decrease in patients after Glenn. Levels of endostatin and its precursor, long-type collagen XVIII, were determined by enzyme-linked immunoassay and immunoprecipitation, respectively, for serum samples from 38 patients undergoing Glenn, total cavopulmonary anastomosis (Fontan), or biventricular repair of cardiac defects. Samples were obtained before surgery and 24 h afterward. In patients undergoing a bidirectional Glenn procedure, endostatin levels decreased after surgery (n = 17; 4.42 vs 3.34 ng/ml; p < 0.001), and long type-collagen XVIII levels increased by 200 % (n = 10; p = 0.0001). However, endostatin levels did not change after surgery in patients undergoing Fontan (n = 13) or biventricular repair (n = 8). In patients undergoing Fontan, long-type collagen XVIII increased by 18 % (p < 0.01), whereas in control subjects, the levels were unchanged. These data suggest that the diversion of hepatic blood flow away from the pulmonary circulation in patients after the Glenn procedure inhibits endostatin production from collagen XVIII, resulting in decreased circulating serum endostatin levels. A decrease in endostatin may promote angiogenesis. The mechanism whereby the pulmonary circulation processes endostatin and its potential role in the pathogenesis of PAVMs warrant further study

Updated Clinical Classification of Pulmonary Hypertension

In 1998, a clinical classification of pulmonary hypertension (PH) was established, categorizing PH into groups which share similar pathological and hemodynamic characteristics and therapeutic approaches. During the 5th World Symposium held in Nice, France, in 2013, the consensus was reached to maintain the general scheme of previous clinical classifications. However, modifications and updates especially for Group 1 patients (pulmonary arterial hypertension [PAH]) were proposed. The main change was to withdraw persistent pulmonary hypertension of the newborn (PPHN) from Group 1 because this entity carries more differences than similarities with other PAH subgroups. In the current classification, PPHN is now designated number 1. Pulmonary hypertension associated with chronic hemolytic anemia has been moved from Group 1 PAH to Group 5, unclear/multifactorial mechanism. In addition, it was decided to add specific items related to pediatric pulmonary hypertension in order to create a comprehensive, common classification for both adults and children. Therefore, congenital or acquired left-heart inflow/outflow obstructive lesions and congenital cardiomyopathies have been added to Group 2, and segmental pulmonary hypertension has been added to Group 5. Last, there were no changes for Groups 2, 3, and 4

Variation in the use of chemotherapy in lung cancer

Factors influencing the use of chemotherapy for the initial (6 months) treatment of lung cancer in South East England were investigated. The variables explored as possibly influencing the use of chemotherapy were sex, age, the year of diagnosis, the type of lung cancer, the stage, the index of multiple deprivation and the cancer network of residence. χ2 analysis and multivariate logistic regression models were used to examine the effect of each of the variables on the use of chemotherapy. The results showed a highly significant trend in use of chemotherapy over time; the adjusted proportion of patients receiving chemotherapy increasing from 13.6% in 1994 to 29.3% in 2003. However, age, cancer network and type of lung cancer had the strongest influence on the use of chemotherapy. This finding is important when we consider that the NHS Cancer Plan aims at improving inequalities in cancer care in the UK

Double aortic arch with double aneuploidy—rare anomaly in combined Down and Klinefelter syndrome

A 14-month-old boy with double aneuploidy and a double aortic arch suffered from frequently recurrent severe feeding and respiratory problems. Chromosomal analysis showed a 48,XXY + 21 karyotype: a double aneuploidy of Down syndrome (DS) and Klinefelter syndrome (KS). Only four cases of double aneuploidy (DS + KS) associated with congenital heart defects have been published of which none had a double aortic arch. Our case report should draw attention to the possibility of a double aortic arch in patients with severe feeding and respiratory problems and a double aneuploidy

Two cultures, one identity: formulations of Australian Isma'ili Muslim identity

The Shi'a Imami Nizari Isma'ili Muslims have often been considered the "poster child" for pluralistic integration (Cayo 2008). This ethos has been inculcated within members of the community, with its adherents seeing themselves as a diverse and multi-ethnic collective. Nevertheless, despite this purported pluralism, social research on the Isma'ilis has primarily focused on the diasporic and post-diasporic migrant communities of South Asian descent, the 'first and second-generation immigrants,' in the Euro-American context (Mukadam and Mawani 2006, 2009; Nanji 1983, 1986). The experiences of co-religionists in other contexts have often been neglected. This study examines how members of the self-described geographically and socially isolated Isma'ili community in Australia construct their identity vis-à-vis the larger, global, Isma'ili community, and how they have responded to the potential of identity threat given the arrival of another group of Isma’ilis with a differing migratory history integrating into the extant community. Using the approach of identity process theory, this study examines how salient features of identity are constructed amongst the Australian Isma'ilis, how religion and identity take on multiple meanings within the Australian Isma'ili context, and, finally, sheds light on the self-sufficiency of this community despite geographic and social isolation

Perlecan Maintains microvessel integrity in vivo and modulates their formation in vitro

Perlecan is a heparan sulfate proteoglycan assembled into the vascular basement membranes (BMs) during vasculogenesis. In the present study we have investigated vessel formation in mice, teratomas and embryoid bodies (EBs) in the absence of perlecan. We found that perlecan was dispensable for blood vessel formation and maturation until embryonic day (E) 12.5. At later stages of development 40% of mutant embryos showed dilated microvessels in brain and skin, which ruptured and led to severe bleedings. Surprisingly, teratomas derived from perlecan-null ES cells showed efficient contribution of perlecan-deficient endothelial cells to an apparently normal tumor vasculature. However, in perlecan-deficient EBs the area occupied by an endothelial network and the number of vessel branches were significantly diminished. Addition of FGF-2 but not VEGF165 rescued the in vitro deficiency of the mutant ES cells. Furthermore, in the absence of perlecan in the EB matrix lower levels of FGFs are bound, stored and available for cell surface presentation. Altogether these findings suggest that perlecan supports the maintenance of brain and skin subendothelial BMs and promotes vasculo- and angiogenesis by modulating FGF-2 function

Casirivimab and imdevimab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Background: Casirivimab and imdevimab are non-competing monoclonal antibodies that bind to two different sites on the receptor binding domain of the SARS-CoV-2 spike glycoprotein, blocking viral entry into host cells. We aimed to evaluate the efficacy and safety of casirivimab and imdevimab administered in combination in patients admitted to hospital with COVID-19. Methods: RECOVERY is a randomised, controlled, open-label platform trial comparing several possible treatments with usual care in patients admitted to hospital with COVID-19. 127 UK hospitals took part in the evaluation of casirivimab and imdevimab. Eligible participants were any patients aged at least 12 years admitted to hospital with clinically suspected or laboratory-confirmed SARS-CoV-2 infection. Participants were randomly assigned (1:1) to either usual standard of care alone or usual care plus casirivimab 4 g and imdevimab 4 g administered together in a single intravenous infusion. Investigators and data assessors were masked to analyses of the outcome data during the trial. The primary outcome was 28-day all-cause mortality assessed by intention to treat, first only in patients without detectable antibodies to SARS-CoV-2 infection at randomisation (ie, those who were seronegative) and then in the overall population. Safety was assessed in all participants who received casirivimab and imdevimab. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). Findings: Between Sept 18, 2020, and May 22, 2021, 9785 patients enrolled in RECOVERY were eligible for casirivimab and imdevimab, of which 4839 were randomly assigned to casirivimab and imdevimab plus usual care and 4946 to usual care alone. 3153 (32%) of 9785 patients were seronegative, 5272 (54%) were seropositive, and 1360 (14%) had unknown baseline antibody status. 812 (8%) patients were known to have received at least one dose of a SARS-CoV-2 vaccine. In the primary efficacy population of seronegative patients, 396 (24%) of 1633 patients allocated to casirivimab and imdevimab versus 452 (30%) of 1520 patients allocated to usual care died within 28 days (rate ratio [RR] 0·79, 95% CI 0·69–0·91; p=0·0009). In an analysis of all randomly assigned patients (regardless of baseline antibody status), 943 (19%) of 4839 patients allocated to casirivimab and imdevimab versus 1029 (21%) of 4946 patients allocated to usual care died within 28 days (RR 0·94, 95% CI 0·86–1·02; p=0·14). The proportional effect of casirivimab and imdevimab on mortality differed significantly between seropositive and seronegative patients (p value for heterogeneity=0·002). There were no deaths attributed to the treatment, or meaningful between-group differences in the pre-specified safety outcomes of cause-specific mortality, cardiac arrhythmia, thrombosis, or major bleeding events. Serious adverse reactions reported in seven (<1%) participants were believed by the local investigator to be related to treatment with casirivimab and imdevimab. Interpretation: In patients admitted to hospital with COVID-19, the monoclonal antibody combination of casirivimab and imdevimab reduced 28-day mortality in patients who were seronegative (and therefore had not mounted their own humoral immune response) at baseline but not in those who were seropositive at baseline. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

A Core Outcome Set for Efficacy of Acute Treatment of Hereditary Angioedema

BACKGROUND: Clinical trials investigating drugs for the acute treatment of hereditary angioedema attacks have assessed many different outcomes. This heterogeneity limits the comparability of trial results and may lead to selective outcome reporting bias and a high burden on trial participants. OBJECTIVE: To achieve consensus on a core outcome set composed of key outcomes that ideally should be used in all clinical efficacy trials involving the acute treatment of hereditary angioedema attacks. METHODS: We conducted a Delphi consensus study involving all relevant parties: patients with hereditary angioedema, hereditary angioedema expert clinicians and clinical researchers, pharmaceutical companies, and regulatory bodies. Two Internetbased survey rounds were conducted. In round 1, panelists indicated the importance of individual outcomes used in clinical trials on a 9 -point Likert scale. Based on these results, a core outcome set was developed and voted on by panelists in round 2. RESULTS: A total of 58 worldwide panelists completed both rounds. The fi rst round demonstrated high importance scores and substantial agreement among the panelists. In the second round, a consensus of 90% or greater was achieved on a core outcome set consisting of fi ve key outcomes: change in overall symptom severity at one predetermined time point between 15 minutes and 4 hours after treatment, time to end of progression of all symptoms, the need for rescue medication during the entire attack, impairment of daily activities, and treatment satisfaction. CONCLUSIONS: This international study obtained a high level of consensus on a core outcome set for the acute treatment of hereditary angioedema attacks, consisting of fi ve key outcomes. Crown Copyright (c) 2024 Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). (J Allergy Clin Immunol Pract 2024;12:1614-21