Latent Risk Subtypes Based on Injection and Sexual Behavior Among People Who Inject Drugs in Rural Puerto Rico

Background—People who inject drugs (PWID) in Puerto Rico engage in high levels of injection and sexual risk behavior, and they are at high risk for HIV and hepatitis C (HCV) infection, relative to their US counterparts. Less is known, however, about the clustering of risk behavior conducive to HIV and HCV infection among rural Puerto Rican communities. Objectives—The purpose of this study was to examine concurrent injection and sexual risk subtypes among a rural sample of PWID in Puerto Rico. Methods—Data were drawn from a respondent-driven sample collected in 2015 of 315 PWID in 4 rural communities approximately 30–40 miles from San Juan. Latent class analysis (LCA) was used to examine risk subtypes using 3 injection and 3 sexual risk indicators. In addition, demographic and other PWID characteristics were examined as possible predictors of latent class membership. Results—Four LCA subtypes were identified: low risk (36%), high injection/low sexual risk (22%), low injection/high sexual risk (20%), and high risk (22%). Younger age and past year homelessness predicted high risk latent class membership, relative to the other classes. In addition, daily speedball use predicted membership in the high injection/low sexual risk class, relative to the low risk and low injection/high sexual risk classes. Conclusion/Importance—The findings suggest ways in which PWID risk clusters can be identified for targeted interventions

Rural and urban injection drug use in Puerto Rico: Network implications for human immunodeficiency virus and hepatitis C virus infection

Understanding the short- and long-term transmission dynamics of blood-borne illnesses in network contexts represents an important public health priority for people who inject drugs and the general population that surrounds them. The purpose of this article is to compare the risk networks of urban and rural people who inject drugs in Puerto Rico. In the current study, network characteristics are drawn from the sampling “trees” used to recruit participants to the study. We found that injection frequency is the only factor significantly related to clustering behavior among both urban and rural people who inject drugs

East Bay Coalition for the Homeless: Branding Study and Marketing Strategy

There are a number of potential positioning strategies. The two which make the most sense for the EBCH are to “position the EBCH away from others in the category” and to “position the EBCH as unique.” These strategies have the advantage of setting the EBCH apart from the other organizations that address homelessness. Occupying its own “position” in the minds of potential and current donors is not only an effective communications/marketing strategy but also a less costly one because it avoids head-to-head competition and comparisons

Mycobacterium tuberculosis progresses through two phases of latent infection in humans

Little is known about the physiology of latent Mycobacterium tuberculosis infection. We studied the mutational rates of 24 index tuberculosis (TB) cases and their latently infected household contacts who developed active TB up to 5.25 years later, as an indication of bacterial physiological state and possible generation times during latent TB infection in humans. Here we report that the rate of new mutations in the M. tuberculosis genome decline dramatically after two years of latent infection (two-sided p < 0.001, assuming an 18 h generation time equal to log phase M. tuberculosis, with latency period modeled as a continuous variable). Alternatively, assuming a fixed mutation rate, the generation time increases over the latency duration. Mutations indicative of oxidative stress do not increase with increasing latency duration suggesting a lack of host or bacterial derived mutational stress. These results suggest that M. tuberculosis enters a quiescent state during latency, decreasing the risk for mutational drug resistance and increasing generation time, but potentially increasing bacterial tolerance to drugs that target actively growing bacteria.publishersversionpublishe

Learning to treat the climate emergency together: social tipping interventions by the health community

Accelerating the decarbonisation of local and national economies is a profound public health imperative. As trusted voices within communities around the world, health professionals and health organisations have enormous potential to influence the social and policy landscape in support of decarbonisation. We assembled a multidisciplinary, gender-balanced group of experts from six continents to develop a framework for maximising the social and policy influence of the health community on decarbonisation at the micro levels, meso levels, and macro levels of society. We identify practical, learning-by-doing approaches and networks to implement this strategic framework. Collectively, the actions of health-care workers can shift practice, finance, and power in ways that can transform the public narrative and influence investment, activate socioeconomic tipping points, and catalyse the rapid decarbonisation needed to protect health and health systems

Impact of Venetoclax and Azacitidine in Treatment-Naïve Patients with Acute Myeloid Leukemia and IDH1/2 Mutations

partially_open16Purpose: To evaluate efficacy and safety of venetoclax + azacitidine among treatment-naïve patients with IDH1/2-mutant (mut) acute myeloid leukemia (AML). Patients and methods: Data were pooled from patients enrolled in a phase III study (NCT02993523) that compared patients treated with venetoclax + azacitidine or placebo + azacitidine and a prior phase Ib study (NCT02203773) where patients were treated with venetoclax + azacitidine. Enrolled patients were ineligible for intensive therapy due to age ≥75 years and/or comorbidities. Patients on venetoclax + azacitidine received venetoclax 400 mg orally (days 1-28) and azacitidine (75 mg/m2; days 1-7/28-day cycle). Results: In the biomarker-evaluable population, IDH1/2mut was detected in 81 (26%) and 28 (22%) patients in the venetoclax + azacitidine and azacitidine groups. Composite complete remission [CRc, complete remission (CR)+CR with incomplete hematologic recovery (CRi)] rates (venetoclax + azacitidine/azacitidine) among patients with IDH1/2mut were 79%/11%, median duration of remission (mDoR) was 29.5/9.5 months, and median overall survival (mOS) was 24.5/6.2 months. CRc rates among patients with IDH1/2 wild-type (WT) were 63%/31%, mDoR 17.5/10.3 months, and mOS 12.3/10.1 months. In patients with IDH1mut, CRc rates (venetoclax + azacitidine/azacitidine) were 66.7%/9.1% and mOS 15.2/2.2 months. In patients with IDH2mut, CRc rates were 86.0%/11.1% and mOS not reached (NR)/13.0 months. Patients with IDH1/2 WT AML treated with venetoclax + azacitidine with poor-risk cytogenetics had inferior outcomes compared with patients with IDH1/2mut, who had superior outcomes regardless of cytogenetic risk (mOS, IDH1/2mut: intermediate-risk, 24.5 months; poor-risk, NR; IDH1/2 WT: intermediate, 19.2 and poor, 7.4 months). There were no unexpected toxicities in the venetoclax + azacitidine group. Conclusions: Patients with IDH1/2mut who received venetoclax + azacitidine had high response rates, durable remissions, and significant OS; cytogenetic risk did not mitigate the favorable outcomes seen from this regimen for IDH1/2mut.partially_openembargoed_20230131Pollyea, Daniel A; DiNardo, Courtney D; Arellano, Martha L; Pigneux, Arnaud; Fiedler, Walter; Konopleva, Marina; Rizzieri, David A; Smith, B Douglas; Shinagawa, Atsushi; Lemoli, Roberto M; Dail, Monique; Duan, Yinghui; Chyla, Brenda; Potluri, Jalaja; Miller, Catherine L; Kantarjian, Hagop MPollyea, Daniel A; Dinardo, Courtney D; Arellano, Martha L; Pigneux, Arnaud; Fiedler, Walter; Konopleva, Marina; Rizzieri, David A; Smith, B Douglas; Shinagawa, Atsushi; Lemoli, Roberto M; Dail, Monique; Duan, Yinghui; Chyla, Brenda; Potluri, Jalaja; Miller, Catherine L; Kantarjian, Hagop

Divergent amino acid and sphingolipid metabolism in patients with inherited neuro-retinal disease

OBJECTIVES: The non-essential amino acids serine, glycine, and alanine, as well as diverse sphingolipid species, are implicated in inherited neuro-retinal disorders and are metabolically linked by serine palmitoyltransferase (SPT), a key enzyme in membrane lipid biogenesis. To gain insight into the pathophysiological mechanisms linking these pathways to neuro-retinal diseases we compared patients diagnosed with two metabolically intertwined diseases: macular telangiectasia type II (MacTel), hereditary sensory autonomic neuropathy type 1 (HSAN1), or both. METHODS: We performed targeted metabolomic analyses of amino acids and broad sphingolipids in sera from a cohort of MacTel (205), HSAN1 (25) and Control (151) participants. RESULTS: MacTel patients exhibited broad alterations of amino acids, including changes in serine, glycine, alanine, glutamate, and branched-chain amino acids reminiscent of diabetes. MacTel patients had elevated 1-deoxysphingolipids but reduced levels of complex sphingolipids in circulation. A mouse model of retinopathy indicates dietary serine and glycine restriction can drive this depletion in complex sphingolipids. HSAN1 patients exhibited elevated serine, lower alanine, and a reduction in canonical ceramides and sphingomyelins compared to controls. Those patients diagnosed with both HSAN1 and MacTel showed the most significant decrease in circulating sphingomyelins. CONCLUSIONS: These results highlight metabolic distinctions between MacTel and HSAN1, emphasize the importance of membrane lipids in the progression of MacTel, and suggest distinct therapeutic approaches for these two neurodegenerative diseases

Role of Adjuvant Multimodality Therapy After Curative-Intent Resection of Ampullary Carcinoma

Importance: Ampullary adenocarcinoma is a rare malignant neoplasm that arises within the duodenal ampullary complex. The role of adjuvant therapy (AT) in the treatment of ampullary adenocarcinoma has not been clearly defined. Objective: To determine if long-term survival after curative-intent resection of ampullary adenocarcinoma may be improved by selection of patients for AT directed by histologic subtype. Design, setting, and participants: This multinational, retrospective cohort study was conducted at 12 institutions from April 1, 2000, to July 31, 2017, among 357 patients with resected, nonmetastatic ampullary adenocarcinoma receiving surgery alone or AT. Cox proportional hazards regression was used to identify covariates associated with overall survival. The surgery alone and AT cohorts were matched 1:1 by propensity scores based on the likelihood of receiving AT or by survival hazard from Cox modeling. Overall survival was compared with Kaplan-Meier estimates. Exposures: Adjuvant chemotherapy (fluorouracil- or gemcitabine-based) with or without radiotherapy. Main outcomes and measures: Overall survival. Results: A total of 357 patients (156 women and 201 men; median age, 65.8 years [interquartile range, 58-74 years]) underwent curative-intent resection of ampullary adenocarcinoma. Patients with intestinal subtype had a longer median overall survival compared with those with pancreatobiliary subtype (77 vs 54 months; P = .05). Histologic subtype was not associated with AT administration (intestinal, 52.9% [101 of 191]; and pancreatobiliary, 59.5% [78 of 131]; P = .24). Patients with pancreatobiliary histologic subtype most commonly received gemcitabine-based regimens (71.0% [22 of 31]) or combinations of gemcitabine and fluorouracil (12.9% [4 of 31]), whereas treatment of those with intestinal histologic subtype was more varied (fluorouracil, 50.0% [17 of 34]; gemcitabine, 44.1% [15 of 34]; P = .01). In the propensity score-matched cohort, AT was not associated with a survival benefit for either histologic subtype (intestinal: hazard ratio, 1.21; 95% CI, 0.67-2.16; P = .53; pancreatobiliary: hazard ratio, 1.35; 95% CI, 0.66-2.76; P = .41). Conclusions and relevance: Adjuvant therapy was more frequently used in patients with poor prognostic factors but was not associated with demonstrable improvements in survival, regardless of tumor histologic subtype. The value of a multimodality regimen remains poorly defined

KELT-24b: A 5MJ Planet on a 5.6day Well-aligned Orbit around the Young V = 8.3 F-star HD 93148

We present the discovery of KELT-24 b, a massive hot Jupiter orbiting a bright (V = 8.3 mag, K = 7.2 mag) young F-star with a period of 5.6 days. The host star, KELT-24 (HD 93148), has a Teff = 6509-+4950 K, a mass of M* = 1.460-+0.0590.055 Me, a radius of R* = 1.506 ± 0.022 Re, and an age of 0.78-+0.420.61 Gyr. Its planetary companion (KELT-24 b) has a radius of RP = 1.272 ± 0.021 RJ and a mass of MP = 5.18-+0.220.21 MJ, and from Doppler tomographic observations, we find that the planet’s orbit is well-aligned to its host star’s projected spin axis (l = 2.6-+3.65.1). The young age estimated for KELT-24 suggests that it only recently started to evolve from the zero-age main sequence. KELT-24 is the brightest star known to host a transiting giant planet with a period between 5 and 10 days. Although the circularization timescale is much longer than the age of the system, we do not detect a large eccentricity or significant misalignment that is expected from dynamical migration. The brightness of its host star and its moderate surface gravity make KELT-24b an intriguing target for detailed atmospheric characterization through spectroscopic emission measurements since it would bridge the current literature results that have primarily focused on lower mass hot Jupiters and a few brown dwarfs

A framework to move forward on the path to eco-innovation in the construction industry: implications to improve firms´ sustainable orientation

This paper examines key aspects in the innovative behavior of the construction firms that determine their environmental orientation while innovating. Structural equation modeling was used and data of 222 firms retrieved from the Spanish Technological Innovation Panel (PITEC) for 2010 to analyse the drivers of environmental orientation of the construction firms during the innovation process. The results show that the environmental orientation is positively affected by the product and process orientation of construction firms during the innovation process. Furthermore, the positive relation between the importance of market information sources and environmental orientation, mediated by process and product orientation, is discussed. Finally, a model that explains these relations is proposed and validated. 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