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Die COVID-19-Pandemie halt weiter an und stellt alle Beteiligten im Gesundheitssystem vor neue und bisher so nie dagewesene Herausforderungen, die sowohl die Strukturen innerhalb von Kliniken sowie des Gesundheitssystems als auch die Kommunikation inter-sowie intradisziplinar betreffen. Die Pandemie macht deutlich, wie wichtig die intersektorale (also zwischen der ambulanten und der stationaren Versorgung), -professionelle und -interdisziplinare Abstimmung ist, um die Versorgung der Patientinnen aufrechtzuerhalten. Dabei gilt es, wiederholt Bestandsaufnahmen vorzunehmen, um zum einen notwendige Anpassungen, zum anderen aber auch Konsequenzen fur zukunftige Entwicklungen zu diskutieren.

This article sets out the background to what has occurred since the issuing of the Uluru Statement from the Heart and provides an overview of the Indigenous Voice Co-Design Interim Report and its Voice design options. In doing so, we discuss the possible progression of Local and Regional Voices and other sub-national legislation on First Nations issues. We analyse how those efforts might be limited and/or extinguished if a First Nations Voice is not constitutionally enshrined when we consider the relationship and legislative powers of the Commonwealth, state, and territory parliaments.

This study examines the types, reasons, and consequences of out-migration in the Uttarakhand Himalaya. Data were collected from secondary sources, mainly from an interim report on the status of migration in revenue villages of Uttarakhand, published by the ‘Rural Development and Migration Commission, Pauri Garhwal, Uttarakhand’ in 2018. The district-wise analysis was carried out on the types of migration, reasons for migration, age-wise migration, the destination of migrants, and migration’s consequences in terms of depopulation in rural areas. Further, a case study of a village was carried out. The study reveals that in three districts – Pauri, Tehri, and Almora, more than 10% population out-migrated after 2011. Similarly, an exodus migration took place from more than 10% of villages of the same districts. This study further shows that migration is mainly internal – from the mountainous districts to urban centers, within the districts or within the state. About 734 villages are depopulated, and in 367 villages, the population has decreased by more than 50%. Unemployment is the major problem in rural areas as more than 50% of out-migration occurred for employment.

Recent excavations at the site of Zincirli Hoyuk in southeastern Turkey have revealed significant remains of the Middle Bronze Age II period, with evidence for local food (and probably wine) produc...

Summary The objective of the present work is to propose a methodology to predict pressure rise due to the thermal expansion of trapped liquids using computational fluid dynamics (CFD). The present study also provides a comparison between the various methods used for pressure buildup calculations that are widely used in oil and gas industries. A comparison of standard thermodynamic calculations with transient 3D CFD analysis reveals that transient CFD analyses can provide deeper insights on the temperature and velocity fields in trapped volumes. The application of the proposed method is not just restricted to a single component/equipment in the subsea field but can be applied to any trapped volume in subsea equipment. In the present study, the pressure buildup in a downhole (DH) port of a subsea Christmas tree (XT) is presented for demonstration purposes; the same methodology can be extended to other equipment or regions of interest. Because of a lack of literature on the topic of pressure rise due to thermal expansion of trapped fluids, engineers are forced to make several assumptions without knowing the effect of each term or parameter on the final pressure calculated. In this study, the percentage change/variation of the final pressure using the various forms of a standard analytical pressure rise equation is also discussed in detail.

Objective: To investigate and compare the effects of maxillary protraction therapy on Class III patients with unilateral cleft lip and palate (UCLP) and Class III patients with noncleft. Design: Prospective controlled clinical trial. Patients: Twenty-six Class III patients with UCLP (mean age: 10.32 ± 1.29 years) and 26 Class III patients with noncleft (mean age: 9.82 ± 1.03 years) were included and treated with maxillary protraction therapy. Interventions: Maxillary protraction therapy was performed with an intraoral Hyrax appliance and extraoral facemask. Cone beam computed tomography scans were taken before and after treatment. Pretreatment skeletal and dental characteristics and treatment changes were analyzed and compared. Results: The average treatment duration was 18.44 ± 4.16 months in the UCLP group, which was substantially longer than the 12.46 ± 4.03-month average treatment duration in the noncleft group ( P < .001). No significant difference was found in the maxillary changes (length, advancement of point A, and SNA angle) and improvement of intermaxillary relationship (ANB angle) between the 2 groups. The UCLP group had 1.40° more mandibular clockwise rotation ( P = .034). Regarding dental changes, the UCLP group had more upper incisor proclination ( P = .006) and less lower incisor retroclination ( P = .023). Conclusions: Approximately extended maxillary protraction therapy in patients with UCLP could be as effective as in patients with noncleft. Further study is required to follow patients until completion of growth to elucidate the long-term stability of the treatment.

The world has continued to change rapidly since the last version of this article was written on May 20, 2020. Yet, as this article goes to press, we are aware of two realities; first, that we cannot perennially chase a moving target, but second, that nothing about the fundamental trends that we have identified appear to have changed. India is firmly in the throes of a vicious pandemic that we can only hope will abate with the development of an effective vaccine. Our plea for the widespread provision of adequate health and medical facilities, adequate protection for the elderly, and transfers to those severely affected by the lockdown are absolutely unchanged in the face of the latest data. In contrast, the brutal enforcement of a lockdown with none of these accompanying measures can only worsen outcomes for the poorest and most vulnerable among the population.

Background COVID-19 poses many challenges to healthcare systems and workers. Responding to medical emergencies in patients with suspected COVID-19 will require new guidelines and protocols. Simulation can support their development. Methods We organised seven simulations involving patients with suspected COVID-19 for staff at Brighton and Sussex University Hospitals. Participants completed pre- and post-simulation questionnaires. Results Fifty-six staff participated and they reported being significantly less prepared to respond to an emergency in a patient with suspected COVID-19 than in one in whom it is not suspected. The simulations significantly improved the participants9 confidence in responding to emergencies in patients with suspected COVID-19. Numerous challenges were identified along the themes of equipment, personnel, communication and procedures. Conclusions Low-fidelity simulation can provide relevant and timely information on how prepared health systems and their workforce are to respond to emergencies. We urge NHS trusts nationally to implement simulations to identify problems and develop effective solutions.

BACKGROUND De novo purine synthesis promotes glioblastoma growth and stemness, invasiveness, and resistance to chemoradiation. Mycophenolate mofetil (MMF) is an FDA-approved inhibitor of de novo purine synthesis that sensitizes glioblastoma to radiation and chemotherapy in mice. This Phase 0/I trial of MMF with Radiotherapy in Recurrent Glioblastoma (NCT04477200) aims to determine the maximum-tolerated dose of MMF that can be combined with radiation,and the extent to which the active metabolite of MMF accumulates in brain tumors and inhibits de novo purine synthesis. METHODS Key eligibility criteria are age ≥18, KPS score ≥60%, and recurrent glioblastoma or gliosarcoma with clinical indication for re-irradiation (phase I) or re-resection/biopsy (phase 0). Patients with tumors involving ≥3 lobes or leptomeningeal space or bevacizumab use within 8 weeks are excluded. MMF 500-2000mg PO BID is given one week pre-operatively in Phase 0 (N=8), and up to 2000mg PO BID (starting 1000mg) on TITE-CRM dose escalation on Phase 1 cohort (N=30). RESULTS Since 7/2020, three Phase 0 and six Phase I subjects have been enrolled. On the phase I cohort, 1500mg BID dose has been reached. Studyrelated toxicities have been limited to mainly grade 1-2 nausea and fatigue. No notable study related hematotoxicity have been noted. Additionally, mass spectrometry-based correlative measurements of the activity of de novo GTP synthesis are ongoing. CONCLUSION MMF has been well tolerated up to 1500mg BID combined with radiotherapy in recurrent glioblastoma patients in this interim analysis. An additional upfront glioblastoma cohort with MMF with standard of care will activate in 2021. These studies will determine the maximum tolerated dose of MMF in combination with radiation and chemotherapy and provide a preliminary efficacy estimate at that dose. Encouraging results would support a randomized clinical trial to determine efficacy of MMF combined with chemoradiation in glioblastoma, and to define potential biomarkers for effectiveness.

BackgroundThe third wave of COVID-19 in England coincided with the rapid spread of the Delta variant of SARS-CoV-2 from the end of May 2021. Case incidence data from the national testing programme (Pillar 2) in England may be affected by changes in testing behaviour and other biases. Community surveys may provide important contextual information to inform policy and the public health response.MethodsWe estimated patterns of community prevalence of SARS-CoV-2 infection in England using RT-PCR swab-positivity, demographic and other risk factor data from round 15 (interim) of the REal-time Assessment of Community Transmission-1 (REACT-1) study (round 15a, carried out from 19 to 29 October 2021). We compared these findings with those from round 14 (9 to 27 September 2021).ResultsDuring mid- to late-October 2021 (round 15a) weighted prevalence was 1.72% (1.61%, 1.84%) compared to 0.83% (0.76%, 0.89%) in September 2021 (round 14). The overall reproduction number (R) from round 14 to round 15a was 1.12 (1.11, 1.14) with increases in prevalence over this period (September to October) across age groups and regions except Yorkshire and The Humber. However, within round 15a (mid- to late-October) there was evidence of a fall in prevalence with R of 0.76 (0.65, 0.88). The highest weighted prevalence was observed among children aged 5 to 12 years at 5.85% (5.10%, 6.70%) and 13 to 17 years at 5.75% (5.02%, 6.57%). At regional level, there was an almost four-fold increase in weighted prevalence in South West from round 14 at 0.59% (0.43%,0.80%) to round 15a at 2.18% (1.84%, 2.58%), with highest smoothed prevalence at subregional level also found in South West in round 15a. Age, sex, key worker status, and presence of children in the home jointly contributed to the risk of swab-positivity. Among the 126 sequenced positive swabs obtained up until 23 October, all were Delta variant; 13 (10.3%) were identified as the AY.4.2 sub-lineage.DiscussionWe observed the highest overall prevalence of swab-positivity seen in the REACT-1 study in England to date in round 15a (October 2021), with a two-fold rise in swab-positivity from round 14 (September 2021). Despite evidence of a fall in prevalence from mid- to late-October 2021, prevalence remains high, particularly in school-aged children, with evidence also of higher prevalence in households with one or more children. Thus, vaccination of children aged 12 and over remains a high priority (with possible extension to children aged 5-12) to help reduce within-household transmission and disruptions to education, as well as among adults, to lessen the risk of serious disease among those infected.

Purpose of review Primary immunodeficiency diseases (PIDs), also called inborn errors of immunity (IEI), are genetic disorders classically characterized by an increased susceptibility to infection and/or disruption in the regulation of an immunologic pathway. This review summarizes and highlights the new IEI disorders in the IUIS 2019 report and 2020 interim report and discusses the directions for the future management of PIDs. Recent findings Since 2017, the International Union of Immunologic Societies (IUIS) IEI committee has updated the IUIS classification of IEIs with 88 new gene defects and 75 new immune disorders. The increased utilization of genetic testing and advances in the strategic evaluation of genetic variants have identified, not only novel IEI disorders, but additional genetic causes for known IEI disorders. Investigation of potential immune susceptibilities during the ongoing COVID-19 pandemic suggests that defects in Type I interferon signalling may underlie more severe disease. Summary The rapid discovery of new IEIs reflects the growing trend of applying genetic testing modalities as part of medical diagnosis and management.In turn, elucidating the pathophysiology of these novel IEIs have enhanced our understanding of how genetic mutations can modulate the immune system and their consequential effect on human health and disease.

Real-life data on the performance of vaccines against SARS-CoV-2 are still limited. We here present the rates of detection and levels of antibodies specific for the SARS-CoV-2 spike protein RBD (receptor binding domain) elicited by four vaccines available in Serbia, including BNT-162b2 (BioNTech/Pfizer), BBIBP-CorV (Sinopharm), Gam-COVID-Vac (Gamaleya Research Institute) and ChAdOx1-S (AstraZeneca), compared with those after documented COVID-19, at 6 weeks and 3 months post first vaccine dose or post-infection. Six weeks post first vaccine dose, specific IgG antibodies were detected in 100% of individuals fully vaccinated with BNT-162b2 (n = 100) and Gam-COVID-Vac (n = 12) and in 81.7% of BBIBP-CorV recipients (n = 148), while one dose of ChAdOx1-S (n = 24) induced specific antibodies in 75%. Antibody levels elicited by BNT-162b2 were higher, while those elicited by BBIBP-CorV were lower, than after SARS-CoV-2 infection. By 3 months post-vaccination, antibody levels decreased but remained ≥20-fold above the cut-off in BNT-162b2 but not in BBIBP-CorV recipients, when an additional 30% were seronegative. For all vaccines, antibody levels were higher in individuals with past COVID-19 than in naïve individuals. A total of twelve new infections occurred within the first 3 months post-vaccination, eight after the first dose of BNT-162b2 and ChAdOx1-S (one each) and BBIBP-CorV (six), and four after full vaccination with BBIBP-CorV, but none required hospitalization.