A new framework for global data regulation

Under the current regulatory framework for data protections, the protection of human rights writ large and the corresponding outcomes are regulated largely independently from the data and tools that both threaten those rights and are needed to protect them. This separation between tools and the outcomes they generate risks overregulation of the data and tools themselves when not linked to sensitive use cases. In parallel, separation risks under-regulation if the data can be collected and processed under a less-restrictive framework, but used to drive an outcome that requires additional sensitivity and restrictions. A new approach is needed to support differential protections based on the genuinely high-risk use cases within each sector. Here, we propose a regulatory framework designed to apply not to specific data or tools themselves, but to the outcomes and rights that are linked to the use of these data and tools in context. This framework is designed to recognize, address, and protect a broad range of human rights, including privacy, and suggests a more flexible approach to policy making that is aligned with current engineering tools and practices. We test this framework in the context of open banking and describe how current privacy-enhancing technologies and other engineering strategies can be applied in this context and that of contract tracing applications. This approach for data protection regulations more effectively builds on existing engineering tools and protects the wide range of human rights defined by legislation and constitutions around the globe.Comment: 15 pages, 2 figure

The effects of perceived COVID-19 threat on compensatory conviction, thought reliance, and attitudes

This research examines how people can defend themselves from the threat associated with the COVID-19 pandemic by relying more on their recently generated thoughts (unrelated to the threat), thus leading those thoughts to have a greater impact on judgement through a meta-cognitive process of thought validation. Study 1 revealed that the impact of the favourability of self-related thoughts on self-esteem was greater for those feeling relatively more (vs. less) threatened by COVID-19. Study 2 manipulated (rather than measured) the favourability of thoughts and assessed the perceived COVID-19 threat. Results also showed that the impact of thoughts on subsequent self-evaluations was greater for those feeling more threatened by COVID-19. Study 3 conceptually replicated the results using a full experimental design by manipulating both thought favourability andthe perceived COVID-19 threat, moving from the self to a social perception paradigm, and providing mediational evidence for the proposed mechanism of compensatory thought validation. A final study addressed some alternative explanations by testing whether the induction of threat used in Study 3 affected perceptions of threat while not having an impact on other featuresMinisterio de Ciencia e Innovación, Gobierno de España (ES), Grant/Award Number: PID2020-116651GB-C31;PID2020- 116651GBC33/AEI/10.13039/501100011033; Consejería de Ciencia, Universidades e Innovación, Comunidad de Madrid, Grant/Award Number: SI3/PJI/2021-0047

Pulse-Echo Quantitative US Biomarkers for Liver Steatosis: Toward Technical Standardization

Excessive liver fat (steatosis) is now the most common cause of chronic liver disease worldwide and is an independent risk factor for cirrhosis and associated complications. Accurate and clinically useful diagnosis, risk stratification, prognostication, and therapy monitoring require accurate and reliable biomarker measurement at acceptable cost. This article describes a joint effort by the American Institute of Ultrasound in Medicine (AIUM) and the RSNA Quantitative Imaging Biomarkers Alliance (QIBA) to develop standards for clinical and technical validation of quantitative biomarkers for liver steatosis. The AIUM Liver Fat Quantification Task Force provides clinical guidance, while the RSNA QIBA Pulse-Echo Quantitative Ultrasound Biomarker Committee develops methods to measure biomarkers and reduce biomarker variability. In this article, the authors present the clinical need for quantitative imaging biomarkers of liver steatosis, review the current state of various imaging modalities, and describe the technical state of the art for three key liver steatosis pulse-echo quantitative US biomarkers: attenuation coefficient, backscatter coefficient, and speed of sound. Lastly, a perspective on current challenges and recommendations for clinical translation for each biomarker is offered

Investigating differences in village-level heterogeneity of malaria infection and household risk factors in Papua New Guinea

Malaria risk is highly heterogeneous. Understanding village and household-level spatial heterogeneity of malaria risk can support a transition to spatially targeted interventions for malaria elimination. This analysis uses data from cross-sectional prevalence surveys conducted in 2014 and 2016 in two villages (Megiar and Mirap) in Papua New Guinea. Generalised additive modelling was used to characterise spatial heterogeneity of malaria risk and investigate the contribution of individual, household and environmental-level risk factors. Following a period of declining malaria prevalence, the prevalence of P. falciparum increased from 11.4 to 19.1% in Megiar and 12.3 to 28.3% in Mirap between 2014 and 2016, with focal hotspots observed in these villages in 2014 and expanding in 2016. Prevalence of P. vivax was similar in both years (20.6% and 18.3% in Megiar, 22.1% and 23.4% in Mirap) and spatial risk heterogeneity was less apparent compared to P. falciparum. Within-village hotspots varied by Plasmodium species across time and between villages. In Megiar, the adjusted odds ratio (AOR) of infection could be partially explained by household factors that increase risk of vector exposure, such as collecting outdoor surface water as a main source of water. In Mirap, increased AOR overlapped with proximity to densely vegetated areas of the village. The identification of household and environmental factors associated with increased spatial risk may serve as useful indicators of transmission hotspots and inform the development of tailored approaches for malaria control

Inguinal Hernia with Splenic Incarceration in a Male Dog

Background: Hernias are changes with the displacement of organs from their normal anatomical location to a newly formed cavity, which can cause pain and dysfunction of the affected organ. The diagnosis can be obtained by palpation or by ultrasound. The treatment of choice is surgical and vision to promote the return of the organ to its normal anatomical position and the closure of the hernial ring. When affixing the edges of the hernial ring is not possible, alternative techniques such as the use of biological or synthetic membranes should be sought. The aim of the present study is to report an atypical case of inguinal hernia with splenic incarceration, in which splenectomy and herniorrhaphy with a bovine phrenic center were performed.  Case: An 8-year-old large mestizo male dog was referred to the Veterinary Hospital of Uberaba complaining of the appearance of a mass in the inguinal region that increased significantly in the last 15 days. On physical examination, there was an increase in volume in the left inguinal region, irreducible and great pain sensitivity in the region. The hemogram showed normochromic normocytic anemia, hyperproteinemia and thrombocytopenia. No changes were observed in the biochemical analyzes. Urinalysis revealed the presence of protein and traces of occult blood. Ultrasound showed an enlarged spleen inside the hernial sac, closing the diagnosis of inguinal hernia. The animal underwent a herniorrhaphy procedure associated with the use of a biological membrane from a bovine phrenic center and splenectomy. In addition, contralateral inguinal hernia was observed. The animal remained hospitalized and under observation for three days. On return, after five days, the guardian reported that the animal was urinating by dripping and had increased volume in the region of the surgery. Urethral catheterization was performed without difficulty and the region of swelling was punctured, obtaining a serosanguinous liquid. Ten days after surgery, stitches were removed and contralateral herniorrhaphy and orchiectomy were recommended. The animal showed complete healing of the surgical wound, but did not return for treatment of the contralateral inguinal hernia.Discussion: Inguinal hernia is considered rare in male dogs, especially in non-neutered animals, and few cases have been described, most of which are over the age of four years. In the present report, the dog is male, not neutered and is eight years old, in line with the findings of the highest occurrence in this species. Inguinal hernia can be hereditary, congenital or acquired from trauma or hormonal changes, and its etiology is poorly understood. The dog in this report acquired this condition in adulthood, and it was not possible to define the cause of the hernia, however it is believed that there is a possibility of muscle weakness associated with the patient's weight. Inguinal hernia in non-neutered dogs usually progresses to inguino-scrotal hernia, and cases in the Brazilian queue breed have been described. In this work, the herniated content was irreducible contrary to what is generally reported. In inguinal hernia, the most observed content is the intestinal loops, but the bladder and colon have already been seen. In the animal in this report, the spleen appeared as herniated content. The diagnosis can be made by palpation when the hernia is reducible, but it does not allow the definition of the hernia content. In cases of incarcerated hernias, it is necessary to perform an ultrasound which also allows the definition of the hernia content. The recommended treatment is surgical by herniorrhaphy, as was done in this patient. During surgery, muscle atrophy was observed in the inguinal region, but the tutor did not authorize the placement of polypropylene mesh for financial reasons. The alternative used and authorized by the tutor was the use of a biological membrane that achieved a satisfactory result, with few complications in the postoperative period

Conformational changes during pore formation by the perforin-related protein pleurotolysin

Membrane attack complex/perforin-like (MACPF) proteins comprise the largest superfamily of pore-forming proteins, playing crucial roles in immunity and pathogenesis. Soluble monomers assemble into large transmembrane pores via conformational transitions that remain to be structurally and mechanistically characterised. Here we present an 11 Å resolution cryo-electron microscopy (cryo-EM) structure of the two-part, fungal toxin Pleurotolysin (Ply), together with crystal structures of both components (the lipid binding PlyA protein and the pore-forming MACPF component PlyB). These data reveal a 13-fold pore 80 Å in diameter and 100 Å in height, with each subunit comprised of a PlyB molecule atop a membrane bound dimer of PlyA. The resolution of the EM map, together with biophysical and computational experiments, allowed confident assignment of subdomains in a MACPF pore assembly. The major conformational changes in PlyB are a ~70° opening of the bent and distorted central β-sheet of the MACPF domain, accompanied by extrusion and refolding of two α-helical regions into transmembrane β-hairpins (TMH1 and TMH2). We determined the structures of three different disulphide bond-trapped prepore intermediates. Analysis of these data by molecular modelling and flexible fitting allows us to generate a potential trajectory of β-sheet unbending. The results suggest that MACPF conformational change is triggered through disruption of the interface between a conserved helix-turn-helix motif and the top of TMH2. Following their release we propose that the transmembrane regions assemble into β-hairpins via top down zippering of backbone hydrogen bonds to form the membrane-inserted β-barrel. The intermediate structures of the MACPF domain during refolding into the β-barrel pore establish a structural paradigm for the transition from soluble monomer to pore, which may be conserved across the whole superfamily. The TMH2 region is critical for the release of both TMH clusters, suggesting why this region is targeted by endogenous inhibitors of MACPF function

Mechanism and disease-association of E2 conjugating enzymes:lessons from UBE2T and UBE2L3

Ubiquitin signalling is a fundamental eukaryotic regulatory system, controlling diverse cellular functions. A cascade of E1, E2, and E3 enzymes is required for assembly of distinct signals, whereas an array of deubiquitinases and ubiquitin-binding modules edit, remove, and translate the signals. In the centre of this cascade sits the E2-conjugating enzyme, relaying activated ubiquitin from the E1 activating enzyme to the substrate, usually via an E3 ubiquitin ligase. Many disease states are associated with dysfunction of ubiquitin signalling, with the E3s being a particular focus. However, recent evidence demonstrates that mutations or impairment of the E2s can lead to severe disease states, including chromosome instability syndromes, cancer predisposition, and immunological disorders. Given their relevance to diseases, E2s may represent an important class of therapeutic targets. In the present study, we review the current understanding of the mechanism of this important family of enzymes, and the role of selected E2s in disease

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research