Assessing the importance of demographic risk factors across two waves of SARS-CoV-2 using fine-scale case data

For the long term control of an infectious disease such as COVID-19, it is crucial to identify the most likely individuals to become infected and the role that differences in demographic characteristics play in the observed patterns of infection. As high-volume surveillance winds down, testing data from earlier periods are invaluable for studying risk factors for infection in detail. Observed changes in time during these periods may then inform how stable thepattern will be in the long term.To this end we analyse the distribution of cases of COVID-19 across Scotland in 2021, where the location (census areas of order 500–1,000 residents) and reporting date of cases are known. We consider over 450,000 individually recorded cases, in two infection waves triggered by different lineages: B.1.1.529 (“Omicron”) and B.1.617.2 (“Delta”). We use random forests, informed by measures of geography, demography, testing and vaccination. We show that the distributions are only adequately explained when considering multiple explanatory variables, implying that case heterogeneity arose from a combination of individual behaviour, immunity, and testing frequency.Despite differences in virus lineage, time of year, and interventions in place, we find the risk factors remained broadly consistent between the two waves. Many of the observed smaller differences could be reasonably explained by changes in control measures

An Integrated Framework for Process-Driven Model Construction in Disease Ecology and Animal Health

Process models that focus on explicitly representing biological mechanisms are increasingly important in disease ecology and animal health research. However, the large number of process modelling approaches makes it difficult to decide which is most appropriate for a given disease system and research question. Here, we discuss different motivations for using process models and present an integrated conceptual analysis that can be used to guide the construction of infectious disease process models and comparisons between them. Our presentation complements existing work by clarifying the major differences between modelling approaches and their relationship with the biological characteristics of the epidemiological system. We first discuss distinct motivations for using process models in epidemiological research, identifying the key steps in model design and use associated with each. We then present a conceptual framework for guiding model construction and comparison, organised according to key aspects of epidemiological systems. Specifically, we discuss the number and type of disease states, whether to focus on individual hosts (e.g., cows) or groups of hosts (e.g., herds or farms), how space or host connectivity affect disease transmission, whether demographic and epidemiological processes are periodic or can occur at any time, and the extent to which stochasticity is important. We use foot-and-mouth disease and bovine tuberculosis in cattle to illustrate our discussion and support explanations of cases in which different models are used to address similar problems. The framework should help those constructing models to structure their approach to modelling decisions and facilitate comparisons between models in the literature

Physical Activity among Asian American Adults: Data from the 2010 Health of Houston Survey

Purpose: The Asian American population represents the fastest growing minority groups in the US; yet, little is still known about physical activity (PA) among Asian Americans. This study examines PA among Asian American adults living in the Houston, TX area. Methods: Data on adults aged 18 and over were drawn from the Health of Houston Survey 2010—a population-based survey focused in the city of Houston and Harris County. PA was operationalized in two ways: number of moderate leisure-time PA days in the past week; and meeting CDC recommendations for aerobic exercise. Multivariate regression models (negative binomial and logistic) were used to compare the PA of Asian Americans with other racial/ethnic groups in the area (white, African American, and Hispanic) and to determine key predictors of PA among Asian Americans and specific Asian ethnic groups (Chinese, Vietnamese, and South Asians). Results: Asians emerged as the only racial/ethnic group that was significantly less likely than whites to have sufficient PA levels (OR=0.66). Both Asians and Hispanics had similarly lower expected numbers of PA days compared to whites (Incidence Rate Ratios or IRR=0.91 and 0.89, respectively), although the effect of being Asian was not significant. Within the Asian sample, Vietnamese had a significantly higher expected number of PA days, compared to their Chinese counterparts (IRR=1.36). Compared to the 18-24 age group, older Asians aged 65 and older had significantly higher expected number of PA days (almost one additional expected day; IRR=1.90) and were 61% more likely to have sufficient PA levels. Low educational achievement and immigrant status were key predictors of decreased PA. Conclusions: Results suggest that Asians are among the least physically active of the major racial/ethnic groups. In contrast to other racial/ethnic groups in the US, older Asians tend to be more active than younger Asians and Asian immigrants are less active than US-born Asians. These findings highlight the need for more targeted and culturally competent interventions to promote physical activity in Asian American communities

Bir izdivacın tarih-i muaşakası

Uşakizade Halit Ziya'nın Hizmet'te tefrika edilen Bir İzdivacın Tarih-i Muaşakası adlı roman

Fluorescence-based endoscopic imaging of Thomsen–Friedenreich antigen to improve early detection of colorectal cancer

Thomsen–Friedenreich (TF) antigen belongs to the mucin-type tumor-associated carbohydrate antigen. Notably, TF antigen is overexpressed in colorectal cancer (CRC) but is rarely expressed in normal colonic tissue. Increased TF antigen expression is associated with tumor invasion and metastasis. In this study, we sought to validate a novel nanobeacon for imaging TF-associated CRC in a preclinical animal model. We developed and characterized the nanobeacon for use with fluorescence colonoscopy. In vivo imaging was performed on an orthotopic rat model of CRC. Both white light and fluorescence colonoscopy methods were utilized to establish the ratio-imaging index for the probe. The nanobeacon exhibited specificity for TF-associated cancer. Fluorescence colonoscopy using the probe can detect lesions at the stage which is not readily confirmed by conventional visualization methods. Further, the probe can report the dynamic change of TF expression as tumor regresses during chemotherapy. Data from this study suggests that fluorescence colonoscopy can improve early CRC detection. Supplemented by the established ratio-imaging index, the probe can be used not only for early detection, but also for reporting tumor response during chemotherapy. Furthermore, since the data obtained through in vivo imaging confirmed that the probe was not absorbed by the colonic mucosa, no registered toxicity is associated with this nanobeacon. Taken together, these data demonstrate the potential of this novel probe for imaging TF antigen as a biomarker for the early detection and prediction of the progression of CRC at the molecular level

Pervasive and non-random recombination in near full-length HIV genomes from Uganda

Recombination is an important feature of HIV evolution, occurring both within and between the major branches of diversity (subtypes). The Ugandan epidemic is primarily composed of two subtypes, A1 and D, that have been co-circulating for 50 years, frequently recombining in dually infected patients. Here, we investigate the frequency of recombinants in this population and the location of breakpoints along the genome. As part of the PANGEA-HIV consortium, 1,472 consensus genome sequences over 5 kb have been obtained from 1,857 samples collected by the MRC/UVRI & LSHTM Research unit in Uganda, 465 (31.6 per cent) of which were near full-length sequences (>8 kb). Using the subtyping tool SCUEAL, we find that of the near full-length dataset, 233 (50.1 per cent) genomes contained only one subtype, 30.8 per cent A1 (n = 143), 17.6 per cent D (n = 82), and 1.7 per cent C (n = 8), while 49.9 per cent (n = 232) contained more than one subtype (including A1/D (n = 164), A1/C (n = 13), C/D (n = 9); A1/C/D (n = 13), and 33 complex types). K-means clustering of the recombinant A1/D genomes revealed a section of envelope (C2gp120-TMgp41) is often inherited intact, whilst a generalized linear model was used to demonstrate significantly fewer breakpoints in the gag-pol and envelope C2-TM regions compared with accessory gene regions. Despite similar recombination patterns in many recombinants, no clearly supported circulating recombinant form (CRF) was found, there was limited evidence of the transmission of breakpoints, and the vast majority (153/164; 93 per cent) of the A1/D recombinants appear to be unique recombinant forms. Thus, recombination is pervasive with clear biases in breakpoint location, but CRFs are not a significant feature, characteristic of a complex, and diverse epidemic

The Need for Laboratory Measurements and Ab Initio Studies to Aid Understanding of Exoplanetary Atmospheres

We are now on a clear trajectory for improvements in exoplanet observations that will revolutionize our ability to characterize their atmospheric structure, composition, and circulation, from gas giants to rocky planets. However, exoplanet atmospheric models capable of interpreting the upcoming observations are often limited by insufficiencies in the laboratory and theoretical data that serve as critical inputs to atmospheric physical and chemical tools. Here we provide an up-to-date and condensed description of areas where laboratory and/or ab initio investigations could fill critical gaps in our ability to model exoplanet atmospheric opacities, clouds, and chemistry, building off a larger 2016 white paper, and endorsed by the NAS Exoplanet Science Strategy report. Now is the ideal time for progress in these areas, but this progress requires better access to, understanding of, and training in the production of spectroscopic data as well as a better insight into chemical reaction kinetics both thermal and radiation-induced at a broad range of temperatures. Given that most published efforts have emphasized relatively Earth-like conditions, we can expect significant and enlightening discoveries as emphasis moves to the exotic atmospheres of exoplanets.Comment: Submitted as an Astro2020 Science White Pape

Retrospective evaluation of the use of pembrolizumab in malignant mesothelioma in a real-world Australian population

Introduction: We investigated the efficacy and toxicity of pembrolizumab in patients with mesothelioma from a real-world Australian population. We aimed to determine clinical factors and predictive biomarkers that could help select patients who are likely to benefit from pembrolizumab. Method: Patients with mesothelioma who were treated with pembrolizumab as part of the Insurance and Care New South Wales compensation scheme were included. Clinical information was collected retrospectively. Tumor biomarkers such as programmed death-ligand 1 (PD-L1), BAP1, and CD3-positive (CD3+) tumor-infiltrating lymphocytes (TILs) were examined using archival formalin-fixed paraffin-embedded tumor samples. Results: A total of 98 patients were included with a median age of 70 years (range, 46–91 y); 92% were men; 76% had epithelioid subtype; 21% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0. Pembrolizumab was used as second-line or subsequent-line treatment in 94 patients and as first-line treatment in four patients. The overall response rate was 18%, and the disease control rate was 56%. The median progression-free survival (PFS) was 4.8 months (95% confidence interval: 3.6–6.2), and the median overall survival (OS) was 9.5 months (95% confidence interval: 6.6–13.7). Immune-related adverse events occurred in 27% of patients, of which nine (9%) were of grade 3 or higher. In the multivariable analysis, factors independently associated with longer PFS included baseline ECOG status of 0 (median PFS: 12 mo versus 4 mo, p < 0.01) and PD-L1 tumor proportion score of greater than or equal to 1% (median PFS: 6 mo versus 4 mo, p < 0.01). Baseline platelet count of less than or equal to 400 × 109/liter was independently associated with longer PFS and OS (median PFS: 6 mo versus 2 mo, p = 0.05; median OS: 10 mo versus 4 mo, p = 0.01), whereas lack of pretreatment dexamethasone was independently associated with OS but not PFS (median OS: 10 mo versus 3 mo, p = 0.01). The odds of response were higher for patients with baseline ECOG status of 0 (p = 0.02) and with greater than or equal to 5% CD3+ TILs in the tumor (p < 0.01). PD-L1 expression, BAP1 loss, and CD3+ TILs in the stroma were not significantly associated with the overall response rate. Conclusions: Immunotherapy is a reasonable treatment option for patients with mesothelioma. Our results are comparable to other clinical trials investigating pembrolizumab in mesothelioma in terms of response. Good performance status assessment remains the most robust predictor for patient outcomes. CD3+ TILs in the tumor may help select patients that are likely to respond to pembrolizumab, whereas factors such as PD-L1 expression, baseline platelet count, and lack of pretreatment dexamethasone may help predict survival outcomes from pembrolizumab treatment

Metastatic breast carcinoma mimicking a sebaceous gland neoplasm: a case report

<p>Abstract</p> <p>Introduction</p> <p>Breast cancer is common in women and its metastases involve the skin in approximately one quarter of patients. Accordingly, metastatic breast cancer shown to be cutaneous through histology must be distinguished from a wide variety of other neoplasms as well as the diverse morphologic variants of breast cancer itself.</p> <p>Case presentation</p> <p>We report the case of a 61-year-old Caucasian woman with cutaneous metastases of a bilateral ductal breast carcinoma that in histopathological examination mimicked an adnexal neoplasm with sebaceous differentiation.</p> <p>Conclusion</p> <p>Against the background of metastatic breast carcinoma, dermatopathological considerations of sebaceous differentiation of skin lesions are presented and discussed focusing on the rare differential diagnosis of sebaceous carcinoma of the breast.</p

Interstate migration of the US poverty population: Immigration “pushes” and welfare magnet “pulls”

This study evaluates the social and demographic structure of poverty migration during the 1985–90 period based on an analysis of recent census data. Particular attention is given to the roles of two policy-relevant factors that are proposed to be linked to poverty migration. The first of these is the role of immigration from abroad and its effect on the net out-migration of longer-term residents with below-poverty incomes, from States receiving the highest volume of immigrants. Such a response, it is argued, could result from job competition or other economic and social costs associated with immigration. The second involves the poverty population “magnet” effect associated with State welfare benefits (AFDC and Food Stamp payments) which has come under renewed scrutiny in light of the impending reform of the federal welfare program. The impact of both of these factors on interstate poverty migration is evaluated in a broader context that takes cognizance of other sociodemographic subgroups, and State-level attributes that are known to be relevant in explaining internal migration. This research employs an exceptionally rich data base of aggregate migration flows, specially tabulated from the full migration sample of the 1990 US census (based on the “residence 5 years ago” question). It also employs an analysis technique, the nested logit model, which identifies separately the “push” and “pull” effects of immigration, welfare benefits, and other State attributes on the migration process. Our findings are fairly clear. The high volume of immigration to selected US States does affect a selective out-migration of the poverty population, which is stronger for whites, Blacks and other non-Asian minorities as well as the least-educated. These results are consistent with arguments that internal migrants are responding to labor market competition from similarly educated immigrants. Moreover, we found that the impact of immigration occurs primarily as a “push” rather than a reduced “pull.” In contrast, State welfare benefits exert only minimal effects on the interstate migration of the poverty population—either as “pulls” or “pushes,” although some demographic segments of that population are more prone to respond than others. In addition to these findings, our results reveal the strong impact that a State's racial and ethnic composition exerts in both retaining and attracting migrants of like race and ethnic groups. This suggests the potential for a greater cross-state division in the US poverty population, by race and ethnic status.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43484/1/11111_2005_Article_BF02208337.pd