Infection of Human Papillomavirus Type 18 and p53 Codon 72 Polymorphism in Lung Cancer Patients From India

Study objectives: Infection with specific high-risk HPV types 16 and 18 and polymorphism of p53 codon 72 has been strongly associated with the genesis of various neoplasms in humans, but such study in lung cancer is limited and the results are controversial. In India, the role of these two factors has been strongly implicated in cervical and other cancers, but the occurrence of HPV or p53 codon 72 polymorphism has not been examined in lung cancer, which is the most common cause of cancer-related death in India. Design and patients: A total of 40 tumor biopsy specimens from advanced lung cancer patients and blood samples from 40 matching control subjects were obtained for the analysis of high-risk HPV types 16 and 18 infection and p53 codon 72 polymorphism by polymerase chain reaction. Results: Only HPV type 18 was detected in 5% (2 of 40 lung cancer patients), but no other HPV could be detected. A significantly increased frequency of Arg/Arg homozygotes was observed in patients with advanced lung cancer when compared to that of control subjects (p = 0.004; odds ratio, 5.13; 95% confidence interval, 1.59 to 17.26). However, no significant correlation could be made between p53 polymorphism and different clinical stages, except for advanced stage IV patients, who showed a higher proportion of Arg/Pro heterozygous genotype. Conclusions: HPV detected in a small proportion of lung cancer patients in India demonstrated an exclusive prevalence of HPV type 18, and there was a significantly higher frequency of p53 Arg/Arg genotype when compared to that of control subjects. Observation of a shorter duration of symptoms (≤ 4 months) in as many as 78% (seven of nine stage IV patients) with Arg/Pro genotype may be an indication that lung cancer patients with the heterozygous p53 genotype are more susceptible to early progression

Infliximab versus second intravenous immunoglobulin for treatment of resistant Kawasaki disease in the USA (KIDCARE): a randomised, multicentre comparative effectiveness trial

Background Although intravenous immunoglobulin (IVIG) is effective therapy for Kawasaki disease, 10–20% of patients have recrudescent fever as a sign of persistent inflammation and require additional treatment. We aimed to compare infliximab with a second infusion of IVIG for treatment of resistant Kawasaki disease. Methods In this multicentre comparative effectiveness trial, patients (aged 4 weeks to 17 years) with IVIG resistant Kawasaki disease and fever at least 36 h after completion of their first IVIG infusion were recruited from 30 hospitals across the USA. Patients were randomly assigned (1:1) to second IVIG (2 g/kg over 8–12 h) or intravenous infliximab (10 mg/kg over 2 h without premedication), by using a randomly permuted block randomisation design with block size of two or four. Patients with fever 24 h to 7 days following completion of first study treatment crossed over to receive the other study treatment. The primary outcome measure was resolution of fever at 24 h after initiation of study treatment with no recurrence of fever attributed to Kawasaki disease within 7 days post-discharge. Secondary outcome measures included duration of fever from enrolment, duration of hospitalisation after randomisation, and changes in markers of inflammation and coronary artery Z score. Efficacy was analysed in participants who received treatment and had available outcome values. Safety was analysed in all randomised patients who did not withdraw consent. This clinical trial is registered with ClinicalTrials.gov, NCT03065244. Findings Between March 1, 2017, and Aug 31, 2020, 105 patients were randomly assigned to treatment and 103 were included in the intention-to-treat population (54 in the infliximab group, 49 in the second IVIG group). Two patients randomised to infliximab did not receive allocated treatment. The primary outcome was met by 40 (77%) of 52 patients in the infliximab group and 25 (51%) of 49 patients in the second IVIG infusion group (odds ratio 0·31, 95% CI 0·13–0·73, p=0·0076). 31 patients with fever beyond 24 h received crossover treatment: nine (17%) in the infliximab group received second IVIG and 22 (45%) in second IVIG group received infliximab (p=0·0024). Three patients randomly assigned to infliximab and two to second IVIG with fever beyond 24h did not receive crossover treatment. Mean fever days from enrolment was 1·5 (SD 1·4) for the infliximab group and 2·5 (2·5) for the second IVIG group (p=0·014). Mean hospital stay was 3·2 days (2·1) for the infliximab group and 4·5 days (2·5) for the second IVIG group (p<0·001). There was no difference between treatment groups for markers of inflammation or coronary artery outcome. 24 (44%) of 54 patients in the infliximab group and 33 (67%) of 49 in the second IVIG group had at least one adverse event. A drop in haemoglobin concentration of at least 2g/dL was seen in 19 (33%) of 58 patients who received IVIG as either their first or second study treatment (three of whom required transfusion) and in three (7%) of 43 who received only infliximab (none required transfusion; p=0·0028). Haemolytic anaemia was the only serious adverse events deemed definitely or probably related to study treatment, and was reported in nine (15%) of 58 patients who received IVIG as either their first or second study treatment and none who received infliximab only. Interpretation Infliximab is a safe, well tolerated, and effective treatment for patients with IVIG resistant Kawasaki disease, and results in shorter duration of fever, reduced need for additional therapy, less severe anaemia, and shorter hospitalisation compared with second IVIG infusion

Nations within a nation: variations in epidemiological transition across the states of India, 1990–2016 in the Global Burden of Disease Study

18% of the world's population lives in India, and many states of India have populations similar to those of large countries. Action to effectively improve population health in India requires availability of reliable and comprehensive state-level estimates of disease burden and risk factors over time. Such comprehensive estimates have not been available so far for all major diseases and risk factors. Thus, we aimed to estimate the disease burden and risk factors in every state of India as part of the Global Burden of Disease (GBD) Study 2016

A gravitational-wave standard siren measurement of the Hubble constant

The detection of GW170817 (ref. 1) heralds the age of gravitational-wave multi-messenger astronomy, with the observations of gravitational-wave and electromagnetic emission from the same transient source. On 17 August 2017 the network of Advanced Laser Interferometer Gravitational-wave Observatory (LIGO)2 and Virgo3 detectors observed GW170817, a strong signal from the merger of a binary neutron-star system. Less than two seconds after the merger, a γ-ray burst event, GRB 170817A, was detected consistent with the LIGO–Virgo sky localization region4–6). The sky region was subsequently observed by optical astronomy facilities7, resulting in the identification of an optical transient signal within about 10 arcseconds of the galaxy NGC 4993 (refs 8–13). GW170817 can be used as a standard siren14–18, combining the distance inferred purely from the gravitational-wave signal with the recession velocity arising from the electromagnetic data to determine the Hubble constant. This quantity, representing the local expansion rate of the Universe, sets the overall scale of the Universe and is of fundamental importance to cosmology. Our measurements do not require any form of cosmic ‘distance ladder’19; the gravitational-wave analysis directly estimates the luminosity distance out to cosmological scales. Here we report H0 = kilometres per second per megaparsec, which is consistent with existing measurements20,21, while being completely independent of them

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Trap filled limit and high current-voltage characteristics of organic diodes with non-zero Schottky barrier

The analytical expressions for trap filled limit voltage (V-TFL') and current - voltage characteristics for non- zero organic Schottky barrier are derived theoretically. The theoretical results are validated experimentally. In this case, the injected free charge carrier density at the contact is not infinitely large but a finite number p(0). For an exponential distribution of traps the maximum possible number of traps that can be filled in a sample is H-b' = H-b((p(0)/N-upsilon))(1/l), where l = T-c/T, T-c is the characteristic temperature of trap distribution. The use of Fermi - Dirac statistics causes a maximum error of only 6.9% in H-b'.The analytical expression for V-TFL' is shown to be V-TFL' = 0.5qH(b)'d(2)/epsilon epsilon(0), where d is the sample thickness. As the applied voltage increases and if p(0) > H-b', V-2 law is obtained over a considerable range of applied voltage. However, the curves change to Ohm's law as the voltage increases beyond this range. If p(0) < H-b', V-2 law is not obtained and the curves directly go to Ohm's law. Experimental results of ITO/PEDOT : PSS/poly(2-methoxy-5-2-ethyhexyloxy) 1,4-phenylenevinylene)(MEH-PPV)/Au and ITO/PEDOT : PSS/poly(3-hexylthiophene)(P3HT)/Au Schottky diodes are reported. The experimental results show excellent agreement with the theory

Effect of illumination intensity and temperature on open circuit voltage in organic solar cells

The effect of illumination intensity and temperature on open circuit voltage (Voc) in organic photovoltaic devices has been investigated. Voc is observed to saturate at high illumination intensities. The illuminated J-V characteristics at different intensities intersect the dark characteristic at a single point. This intersection point is shown to be equal to the built-in voltage (Vbi) in the sample. A reduction in temperature shows increment in saturated Voc. This increment in saturated Voc is attributed to the variation of Vbi with temperature. A model has been presented that explains the observed behavior of Vbi at different temperatures