We perform tunneling measurements on indium antimonide nanowire-superconductor hybrid devices fabricated for the studies of Majorana bound states. At finite magnetic field, resonances that strongly ...resemble Majorana bound states, including zero-bias pinning, become common to the point of ubiquity. Since Majorana bound states are predicted in only a limited parameter range in nanowire devices, we seek an alternative explanation for the observed zero-bias peaks. With the help of a self-consistent Poission-Schrödinger multiband model developed in parallel, we identify several families of trivial subgap states that overlap and interact, giving rise to a crowded spectrum near zero energy and zero-bias conductance peaks in experiments. These findings advance the search for Majorana bound states through improved understanding of broader phenomena found in superconductor-semiconductor systems.
This is a cross-sectional, observational study to determine the frequency and associated features of HIV-associated neurocognitive disorders (HAND) in a large, diverse sample of infected individuals ...in the era of combination antiretroviral therapy (CART).
A total of 1,555 HIV-infected adults were recruited from 6 university clinics across the United States, with minimal exclusions. We used standardized neuromedical, psychiatric, and neuropsychological (NP) examinations, and recently published criteria for diagnosing HAND and classifying 3 levels of comorbidity (minimal to severe non-HIV risks for NP impairment).
Fifty-two percent of the total sample had NP impairment, with higher rates in groups with greater comorbidity burden (40%, 59%, and 83%). Prevalence estimates for specific HAND diagnoses (excluding severely confounded cases) were 33% for asymptomatic neurocognitive impairment, 12% for mild neurocognitive disorder, and only 2% for HIV-associated dementia (HAD). Among participants with minimal comorbidities (n = 843), history of low nadir CD4 was a strong predictor of impairment, and the lowest impairment rate on CART occurred in the subset with suppressed plasma viral loads and nadir CD4 ≥200 cells/mm(3) (30% vs 47% in remaining subgroups).
The most severe HAND diagnosis (HAD) was rare, but milder forms of impairment remained common, even among those receiving CART who had minimal comorbidities. Future studies should clarify whether early disease events (e.g., profound CD4 decline) may trigger chronic CNS changes, and whether early CART prevents or reverses these changes.
Summary Background Cancer is a major cause of death in children worldwide, and the recorded incidence tends to increase with time. Internationally comparable data on childhood cancer incidence in the ...past two decades are scarce. This study aimed to provide internationally comparable local data on the incidence of childhood cancer to promote research of causes and implementation of childhood cancer control. Methods This population-based registry study, devised by the International Agency for Research on Cancer in collaboration with the International Association of Cancer Registries, collected data on all malignancies and non-malignant neoplasms of the CNS diagnosed before age 20 years in populations covered by high-quality cancer registries with complete data for 2001–10. Incidence rates per million person-years for the 0–14 years and 0–19 years age groups were age-adjusted using the world standard population to provide age-standardised incidence rates (WSRs), using the age-specific incidence rates (ASR) for individual age groups (0–4 years, 5–9 years, 10–14 years, and 15–19 years). All rates were reported for 19 geographical areas or ethnicities by sex, age group, and cancer type. The regional WSRs for children aged 0–14 years were compared with comparable data obtained in the 1980s. Findings Of 532 invited cancer registries, 153 registries from 62 countries, departments, and territories met quality standards, and contributed data for the entire decade of 2001–10. 385 509 incident cases in children aged 0–19 years occurring in 2·64 billion person-years were included. The overall WSR was 140·6 per million person-years in children aged 0–14 years (based on 284 649 cases), and the most common cancers were leukaemia (WSR 46·4), followed by CNS tumours (WSR 28·2), and lymphomas (WSR 15·2). In children aged 15–19 years (based on 100 860 cases), the ASR was 185·3 per million person-years, the most common being lymphomas (ASR 41·8) and the group of epithelial tumours and melanoma (ASR 39·5). Incidence varied considerably between and within the described regions, and by cancer type, sex, age, and racial and ethnic group. Since the 1980s, the global WSR of registered cancers in children aged 0–14 years has increased from 124·0 (95% CI 123·3–124·7) to 140·6 (140·1–141·1) per million person-years. Interpretation This unique global source of childhood cancer incidence will be used for aetiological research and to inform public health policy, potentially contributing towards attaining several targets of the Sustainable Development Goals. The observed geographical, racial and ethnic, age, sex, and temporal variations require constant monitoring and research. Funding International Agency for Research on Cancer and the Union for International Cancer Control.
A fatal transmissible tumor spread between individuals by biting has emerged in the Tasmanian devil (Sarcophilus harrisii), a carnivorous marsupial. Here we provide genetic evidence establishing that ...the tumor is clonal and therefore foreign to host devils. Thus, the disease is highly unusual because it is not just a tumor but also a tissue graft, passed between individuals without invoking an immune response. The MHC plays a key role in immune responses to both tumors and grafts. The most common mechanism of immune evasion by tumors is down-regulation of classical cell surface MHC molecules. Here we show that this mode of immune escape does not occur. However, because the tumor is a graft, it should still be recognized and rejected by the host's immune system due to foreign cell surface antigens. Mixed lymphocyte responses showed a lack of alloreactivity between lymphocytes of different individuals in the affected population, indicating a paucity of MHC diversity. This result was verified by genotyping, providing a conclusive link between a loss of MHC diversity and spread of a disease through a wild population. This novel disease arose as a direct result of loss of genetic diversity and the aggressive behavior of the host species. The neoplastic clone continues to spread although the population, and, without active disease control by removal of affected animals and the isolation of disease-free animals, the Tasmanian devil faces extinction.
The incidence of asthma is increasing worldwide, but morbidity and mortality are decreasing because of improvements in medical care. Although the incidence of severe perioperative bronchospasm is ...relatively low in asthmatics undergoing anaesthesia, when it does occur it may be life-threatening. The keys to an uncomplicated perioperative course are assiduous attention to detail in preoperative assessment, and maintenance of the anti-inflammatory and bronchodilatory regimens through the perioperative period. Potential trigger agents should be identified and avoided. Many routinely used anaesthetic agents have an ameliorative effect on airway constriction. Nonetheless, acute bronchospasm can still occur, especially at induction and emergence, and should be promptly and methodically managed.
The Southern Province of Sri Lanka is endemic with dengue, with frequent outbreaks and occurrence of severe disease. However, the economic burden of dengue is poorly quantified. Therefore, we ...conducted a cost analysis to assess the direct and indirect costs associated with hospitalized patients with dengue to households and to the public healthcare system.
From June 2017-December 2018, we prospectively enrolled children and adults with acute dengue hospitalized at the largest, public tertiary-care (1800 bed) hospital in the Southern Province, Sri Lanka. We administered a structured questionnaire to obtain information regarding direct costs spent by households on medical visits, medications, laboratory testing, and travel for seeking care for the illness. Indirect costs lost by households were estimated by identifying the days of work lost by patients and caregivers and school days lost by children. Direct hospital costs were estimated using gross costing approach and adjusted by multiplying by annual inflation rates in Sri Lankan rupees and converted to US dollars.
A total of 1064 patients with laboratory-confirmed dengue were enrolled. The mean age (SD) was 35.9 years (15.6) with male predominance (66.2%). The mean durations of hospitalization for adults and paediatric patients were 3.86 (SD = 1.51) and 4 (SD = 1.32) days, respectively. The per-capita direct cost borne by the healthcare system was 233.76 USD, and was approximately 14 times greater than the per-capita direct cost borne by households (16.29 USD, SD = 14.02). The per-capita average number of loss of working days was 21.51 (SD = 41.71), with mean per-capita loss of income due to loss of work being 303.99 USD (SD = 569.77), accounting for over 70% of average monthly income. On average, 10.88 days (SD = 10.97) of school days were missed due to the dengue episode. School misses were expected to reduce future annual income of affected children by 0.44%.
Dengue requiring hospitalization had a substantial economic burden on the public healthcare system in Sri Lanka and the affected households. These findings emphasize the importance of strengthening dengue control activities and improved use of hospital-based resources for care to reduce the economic impact of dengue in Sri Lanka.
Within the Burkholderia cepacia complex (Bcc), B. cenocepacia portends increased mortality compared with other species. We investigated the impact of Bcc infection on mortality and re‐infection ...following lung transplant (LT). Species designation for isolates from Bcc‐infected patients was determined using 16S rDNA and recA gene analyses. Of 75 cystic fibrosis patients undergoing LT from September 1992 to August 2002, 59 had no Bcc and 16 had Bcc (including 7 B. cenocepacia) isolated in the year before LT. Of the latter, 87.5% had Bcc recovered after transplantation, and all retained their pretransplant strains. Survival was 97%, 92%, 76% and 63% for noninfected patients; 89%, 89%, 67% and 56% for patients infected with Bcc species other than B. cenocepacia; and 71%, 29%, 29% and 29% for patients with B. cenocepacia (p = 0.014) at 1 month, 1 year, 3 years and 5 years, respectively. Patients infected with B. cenocepacia before transplant were six times more likely to die within 1 year of transplant than those infected with other Bcc species (p = 0.04) and eight times than noninfected patients (p < 0.00005). Following LT, infection with Bcc species other than B. cenocepacia does not significantly impact 5‐year survival whereas infection with B. cenocepacia pretransplant is associated with decreased survival.
Survival following lung transplantation was compared among cystic fibrosis patients infected with Burkholderia cepacia complex (Bcc) prior to transplant and infection with Bcc species other than B. cenocepacia did not significantly impact 5 year survival, whereas infection with B. cenocepacia was associated with decreased survival
Three types of HIV-associated neurocognitive disorders (HAND) exist that are distinguished by presence and severity of impairment in cognitive and everyday functioning. Although well-validated ...neurocognitive measures exist, determining impairment in everyday functioning remains a challenge. We aim to determine whether Self-Report measures of everyday functioning are as effective in characterizing HAND as Performance-Based measures. We assessed 674 HIV-infected participants with a comprehensive neurocognitive battery; 233 met criteria for a HAND diagnosis by having at least mild neurocognitive impairment. Functional decline was measured via Self-Report and Performance-Based measures. HAND diagnoses were determined according to published criteria using three approaches to assess functional decline: (1) Self-Report measures only, (2) Performance-Based measures only, and (3) Dual-method combining Self-Report and Performance-Based measures. The Dual-method classified the most symptomatic HAND, compared to either singular method. Singular method classifications were 76% concordant with each other. Participants classified as Performance-Based functionally impaired were more likely to be unemployed and more immunosuppressed, whereas those classified as Self-Report functionally impaired had more depressive symptoms. Multimodal methods of assessing everyday functioning facilitate detection of symptomatic HAND. Singular Performance-Based classifications were associated with objective functional and disease-related factors; reliance on Self-Report classifications may be biased by depressive symptoms.
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