Capabilities of parity check codes for nonprime alphabets

Thesis: M.S., Massachusetts Institute of Technology, Department of Electrical Engineering, 1964Includes bibliographical references (leaf 28).by Joseph Elliot Levy.M.S.M.S. Massachusetts Institute of Technology, Department of Electrical Engineerin

Questioning loneliness: an exploration of the research discourses related to stroke survival in a remote rural community in Scotland

Gail Carin-Levy - ORCID: 0000-0001-6487-3343 https://orcid.org/0000-0001-6487-3343Michelle Elliot - ORCID: 0000-0002-0181-5581 https://orcid.org/0000-0002-0181-5581This paper reflects on a pilot study exploring the loneliness experiences of stroke survivors living in remote rural communities in Scotland. Empirical evidence gathered at the time of establishing this study demonstrated that there were no studies published around the subjective experiences of stroke survivors living alone in remote rural Scottish communities. Yet, stroke survivors in rural settings in other parts of the world report a longing for social contact as well as the experience of a reduction in participation in shared activities, suggestive of potential loneliness and isolation. This paper focuses on our experience interviewing one participant recruited in the early stages of the COVID-19 pandemic. Due to the pandemic, the study had to be terminated, but we were left with data gathered from this one conversation which revealed a rich narrative centred around past and present occupations. At no point was there any sense of loneliness expressed, despite the context within which this participant lived: alone, in a remote community, experiencing a degree of communication difficulties and unable to leave the house independently. All commonly hallmark ‘warning signs’ of a person at risk of loneliness. In this reflection we offer perspectives on assumptions and expectations of loneliness that are problematically constructed by the dominant narratives and theories at the time.Funding for project expenses received by CASS, QMUhttps://bristoluniversitypressdigital.com/view/journals/jps/aop/article-10.1332-14786737Y2024D000000013/article-10.1332-14786737Y2024D000000013.xml?tab_body=pdfhttps://doi.org/10.1332/14786737Y2024D000000013aheadofprintaheadofprin

HSD3B1 genotype identifies glucocorticoid responsiveness in severe asthma

Asthma resistance to glucocorticoid treatment is a major health problem with unclear etiology. Glucocorticoids inhibit adrenal androgen production. However, androgens have potential benefits in asthma. HSD3B1 encodes for 3β-hydroxysteroid dehydrogenase-1 (3β-HSD1), which catalyzes peripheral conversion from adrenal dehydroepiandrosterone (DHEA) to potent androgens and has a germline missense-encoding polymorphism. The adrenal restrictive HSD3B1(1245A) allele limits conversion, whereas the adrenal permissive HSD3B1(1245C) allele increases DHEA metabolism to potent androgens. In the Severe Asthma Research Program (SARP) III cohort, we determined the association between DHEA-sulfate and percentage predicted forced expiratory volume in 1 s (FEV1PP). HSD3B1(1245) genotypes were assessed, and association between adrenal restrictive and adrenal permissive alleles and FEV1PP in patients with (GC) and without (noGC) daily oral glucocorticoid treatment was determined (n = 318). Validation was performed in a second cohort (SARP I&II; n = 184). DHEA-sulfate is associated with FEV1PP and is suppressed with GC treatment. GC patients homozygous for the adrenal restrictive genotype have lower FEV1PP compared with noGC patients (54.3% vs. 75.1%; P < 0.001). In patients with the homozygous adrenal permissive genotype, there was no FEV1PP difference in GC vs. noGC patients (73.4% vs. 78.9%; P = 0.39). Results were independently confirmed: FEV1PP for homozygous adrenal restrictive genotype in GC vs. noGC is 49.8 vs. 63.4 (P < 0.001), and for homozygous adrenal permissive genotype, it is 66.7 vs. 67.7 (P = 0.92). The adrenal restrictive HSD3B1(1245) genotype is associated with GC resistance. This effect appears to be driven by GC suppression of 3β-HSD1 substrate. Our results suggest opportunities for prediction of GC resistance and pharmacologic intervention

The influence of air-sea fluxes on atmospheric aerosols during the summer monsoon over the tropical Indian Ocean

During the summer monsoon, the western tropical Indian Ocean is predicted to be a hot spot for dimethylsulfide emissions, the major marine sulfur source to the atmosphere, and an important aerosol precursor. Other aerosol relevant fluxes, such as isoprene and sea spray, should also be enhanced, due to the steady strong winds during the monsoon. Marine air masses dominate the area during the summer monsoon, excluding the influence of continentally derived pollutants. During the SO234-2/235 cruise in the western tropical Indian Ocean from July to August 2014, directly measured eddy covariance DMS fluxes confirm that the area is a large source of sulfur to the atmosphere (cruise average 9.1 μmol m−2 d−1). The directly measured fluxes, as well as computed isoprene and sea spray fluxes, were combined with FLEXPART backward and forward trajectories to track the emissions in space and time. The fluxes show a significant positive correlation with aerosol data from the Terra and Suomi-NPP satellites, indicating a local influence of marine emissions on atmospheric aerosol numbers

Estradiol and mTORC2 cooperate to enhance prostaglandin biosynthesis and tumorigenesis in TSC2-deficient LAM cells

Lymphangioleiomyomatosis (LAM) is a progressive neoplastic disorder that leads to lung destruction and respiratory failure primarily in women. LAM is typically caused by tuberous sclerosis complex 2 (TSC2) mutations resulting in mTORC1 activation in proliferative smooth muscle–like cells in the lung. The female predominance of LAM suggests that estradiol contributes to disease development. Metabolomic profiling identified an estradiol-enhanced prostaglandin biosynthesis signature in Tsc2-deficient (TSC−) cells, both in vitro and in vivo. Estradiol increased the expression of cyclooxygenase-2 (COX-2), a rate-limiting enzyme in prostaglandin biosynthesis, which was also increased at baseline in TSC-deficient cells and was not affected by rapamycin treatment. However, both Torin 1 treatment and Rictor knockdown led to reduced COX-2 expression and phospho-Akt-S473. Prostaglandin production was also increased in TSC-deficient cells. In preclinical models, both Celecoxib and aspirin reduced tumor development. LAM patients had significantly higher serum prostaglandin levels than healthy women. 15-epi-lipoxin-A4 was identified in exhaled breath condensate from LAM subjects and was increased by aspirin treatment, indicative of functional COX-2 expression in the LAM airway. In vitro, 15-epi-lipoxin-A4 reduced the proliferation of LAM patient–derived cells in a dose-dependent manner. Targeting COX-2 and prostaglandin pathways may have therapeutic value in LAM and TSC-related diseases, and possibly in other conditions associated with mTOR hyperactivation

Durvalumab in Combination with Olaparib in Patients with Relapsed SCLC: Results from a Phase II Study

Purpose: Despite high tumor mutationburden, immune checkpoint blockade has limited efficacy in SCLC. We hypothesized that poly (ADP-ribose) polymerase inhibition could render SCLC more susceptible to immune checkpoint blockade. Methods: A single-arm, phase II trial (NCT02484404) enrolled patients with relapsed SCLC who received durvalumab, 1500 mg every 4 weeks, and olaparib, 300 mg twice a day. The primary outcome was objective response rate. Correlative studies included mandatory collection of pretreatment and during-treatment biopsy specimens, which were assessed to define SCLC immunephenotypes: desert (CD8-positive T-cell prevalence low), excluded (CD8-positive T cells in stroma immediately adjacent/within tumor), and inflamed (CD8-positive T cells in direct contact with tumor). Results: A total of 20 patients were enrolled. Their median age was 64 years, and most patients (60%) had platinum-resistant/refractory disease. Of 19 evaluable patients, two were observed to have partial or complete responses (10.5%), including a patient with EGFR-transformed SCLC. Clinical benefit was observed in four patients (21.1% [95% confidence interval: 6.1%–45.6%]) with confirmed responses or prolonged stable disease (≥8 months). The most common treatment-related adverse events were anemia (80%), lymphopenia (60%), and leukopenia (50%). Nine of 14 tumors (64%) exhibited an excluded phenotype; 21% and 14% of tumors exhibited the inflamed and desert phenotypes, respectively. Tumor responses were observed in all instances in which pretreatment tumors showed an inflamed phenotype. Of the five tumors without an inflamed phenotype at baseline, no during-treatment increase in T-cell infiltration or programmed death ligand 1 expression on tumor-infiltrating immune cells was observed. Conclusions: The study combination did not meet the preset bar for efficacy. Pretreatment and during-treatment biopsy specimens suggested that tumor immune phenotypes may be relevant for SCLC responses to immune checkpoint blockade combinations. The predictive value of preexisting CD8-positive T-cell infiltrates observed in this study needs to be confirmed in larger cohorts

Spin injection and spin accumulation in all-metal mesoscopic spin valves

We study the electrical injection and detection of spin accumulation in lateral ferromagnetic metal-nonmagnetic metal-ferromagnetic metal (F/N/F) spin valve devices with transparent interfaces. Different ferromagnetic metals, permalloy (Py), cobalt (Co) and nickel (Ni), are used as electrical spin injectors and detectors. For the nonmagnetic metal both aluminium (Al) and copper (Cu) are used. Our multi-terminal geometry allows us to experimentally separate the spin valve effect from other magneto resistance signals such as the anomalous magneto resistance (AMR) and Hall effects. We find that the AMR contribution of the ferromagnetic contacts can dominate the amplitude of the spin valve effect, making it impossible to observe the spin valve effect in a 'conventional' measurement geometry. In a 'non local' spin valve measurement we are able to completely isolate the spin valve signal and observe clear spin accumulation signals at T=4.2 K as well as at room temperature (RT). For aluminum we obtain spin relaxation lengths (lambda_{sf}) of 1.2 mu m and 600 nm at T=4.2 K and RT respectively, whereas for copper we obtain 1.0 mu m and 350 nm. The spin relaxation times tau_{sf} in Al and Cu are compared with theory and results obtained from giant magneto resistance (GMR), conduction electron spin resonance (CESR), anti-weak localization and superconducting tunneling experiments. The spin valve signals generated by the Py electrodes (alpha_F lambda_F=0.5 [1.2] nm at RT [T=4.2 K]) are larger than the Co electrodes (alpha_F lambda_F=0.3 [0.7] nm at RT [T=4.2 K]), whereas for Ni (alpha_F lambda_F<0.3 nm at RT and T=4.2 K) no spin signal is observed. These values are compared to the results obtained from GMR experiments.Comment: 16 pages, 12 figures, submitted to PR

Cost-Effectiveness of Male Circumcision for HIV Prevention in a South African Setting

BACKGROUND: Consistent with observational studies, a randomized controlled intervention trial of adult male circumcision (MC) conducted in the general population in Orange Farm (OF) (Gauteng Province, South Africa) demonstrated a protective effect against HIV acquisition of 60%. The objective of this study is to present the first cost-effectiveness analysis of the use of MC as an intervention to reduce the spread of HIV in sub-Saharan Africa. METHODS AND FINDINGS: Cost-effectiveness was modeled for 1,000 MCs done within a general adult male population. Intervention costs included performing MC and treatment of adverse events. HIV prevalence was estimated from published estimates and incidence among susceptible subjects calculated assuming a steady-state epidemic. Effectiveness was defined as the number of HIV infections averted (HIA), which was estimated by dynamically projecting over 20 years the reduction in HIV incidence observed in the OF trial, including secondary transmission to women. Net savings were calculated with adjustment for the averted lifetime duration cost of HIV treatment. Sensitivity analyses examined the effects of input uncertainty and program coverage. All results were discounted to the present at 3% per year. For Gauteng Province, assuming full coverage of the MC intervention, with a 2005 adult male prevalence of 25.6%, 1,000 circumcisions would avert an estimated 308 (80% CI 189–428) infections over 20 years. The cost is $181 (80$117–$306) per HIA, and net savings are$2.4 million (80% CI $1.3 million to$3.6 million). Cost-effectiveness is sensitive to the costs of MC and of averted HIV treatment, the protective effect of MC, and HIV prevalence. With an HIV prevalence of 8.4%, the cost per HIA is $551 (80$344–$1,071) and net savings are$753,000 (80% CI $0.3 million to$1.2 million). Cost-effectiveness improves by less than 10% when MC intervention coverage is 50% of full coverage. CONCLUSIONS: In settings in sub-Saharan Africa with high or moderate HIV prevalence among the general population, adult MC is likely to be a cost-effective HIV prevention strategy, even when it has a low coverage. MC generates large net savings after adjustment for averted HIV medical costs

Regional Chemotherapy in Locally Advanced Pancreatic Cancer: RECLAP Trial

<p>Abstract</p> <p>Background</p> <p>Pancreatic cancer is the fourth leading cause of cancer death in the United States. Surgery offers the only chance for cure. However, less than twenty percent of patients are considered operative candidates at the time of diagnosis. A common reason for being classified as unresectable is advanced loco-regional disease.</p> <p>A review of the literature indicates that almost nine hundred patients with pancreatic cancer have received regional chemotherapy in the last 15 years. Phase I studies have shown regional administration of chemotherapy to be safe. The average reported response rate was approximately 26%. The average 1-year survival was 39%, with an average median survival of 9 months. Of the patients that experienced a radiographic response to therapy, 78 (78/277, 28%) patients underwent exploratory surgery following regional chemotherapy administration; thirty-two (41%) of those patients were amenable to pancreatectomy. None of the studies performed analyses to identify factors predicting response to regional chemotherapy.</p> <p>Progressive surgical techniques combined with current neoadjuvant chemoradiotherapy strategies have already yielded emerging support for a multimodality approach to treatment of advanced pancreatic cancer.</p> <p>Intravenous gemcitabine is the current standard treatment of pancreatic cancer. However, >90% of the drug is secreted unchanged affecting toxicity but not the cancer per se. Gemcitabine is converted inside the cell into its active drug form in a rate limiting reaction. We hypothesize that neoadjuvant regional chemotherapy with continuous infusion of gemcitabine will be well tolerated and may improve resectability rates in cases of locally advanced pancreatic cancer.</p> <p>Design</p> <p>This is a phase I study designed to evaluate the feasibility and toxicity of super-selective intra-arterial administration of gemcitabine in patients with locally advanced, unresectable pancreatic adenocarcinoma. Patients considered unresectable due to locally advanced pancreatic cancer will receive super-selective arterial infusion of gemcitabine over 24 hours via subcutaneous indwelling port. Three to six patients will be enrolled per dose cohort, with seven cohorts, plus an additional six patients at the maximum tolerated dose; accrual is expected to last 36 months. Secondary objectives will include the determination of progression free and overall survival, as well as the conversion rate from unresectable to potentially resectable pancreatic cancer.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov ID: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01294358">NCT01294358</a></p

Circadian rhythm of urinary pH in man with and without chronic antacid administration

In normal human volunteers, when urinary pH was plotted versus time, the circadian sine-wave type curve was not altered by chronic administration of a commercially available suspension containing a mixture of magnesium and aluminum hydroxides, although the antacid perturbed the entire curve in a more alkaline direction. A single dose of the antacid had little effect on urinary pH. There was a highly significant linear relationship between the change in hydrogen ion concentration during chronic antacid treatment and the initial control urinary hydrogen ion concentration, but there was no significant correlation between change in urinary pH and initial control urinary pH as has been previously reported. The above results were based on the evaluation of the hydrogen ion concentrations of 1562 separate urine samples collected from 24 normal subjects in a three treatment crossover study. It is recommended that: (1) research studies involving drug-drug interactions with antacids be designed to consider the effect of the antacid on the circadian rhythm of urinary pH, and (2) pH values not be averaged as commonly reported in the literature, but rather the pH values be converted to hydrogen ion concentrations before statistical analysis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46636/1/228_2004_Article_BF00561060.pd