Copper(I) Complexes of Heterocyclic Thiourea Ligands

The coordination of heterocyclic thiourea ligands (L = N-(2-pyridyl)-N′-phenylthiourea (1), N-(2-pyridyl)-N′-methylthiourea (2), N-(3-pyridyl)-N′-phenylthiourea (3), N-(3-pyridyl)-N′-methylthiourea (4), N-(4-pyridyl)-N′-phenylthiourea (5), N-(2-pyrimidyl)-N′-phenylthiourea (6), N-(2-pyrimidyl)-N′-methylthiourea (7), N-(2-thiazolyl)-N′-methylthiourea (8), N-(2-benzothiazolyl)-N′-methylthiourea (9), N,N′-bis(2-pyridyl)thiourea (10) and N,N′-bis(3-pyridyl)thiourea (11)) with CuX (X = Cl, Br, I, NO3) has been investigated. CuX:L product stoichiometries of 1:1–1:5 were found, with 1:1 being most common. X-ray structures of four 3-coordinate mononuclear CuXL2 complexes (CuCl(6)2, CuCl(7)2, CuBr(6)2, and CuBr(9)2) are reported. In contrast, CuBr(1)2 is a 1D sulfur-bridged polymer. CuIL structures (L = 7, 8) are 1D chains with corner-sharing Cu2(μ-I)2 and Cu2(μ-S)2 units, and CuCl(10) is a 2D network having μ-Cl and N-/S-bridging L. Two [CuL2]NO3 structures are reported: a mononuclear 4-coordinate copper complex with chelating ligands (L = 10) and a 1D link-chain with N-/S-bridging L (L = 3). Two ligand oxidative cyclizations were encountered during crystallization. CuI crystallized with 6 to produce zigzag ladder polymer [(CuI)2(12)]·½CH3CN (12 = N-(pyrimidin-2-yl)benzo[d]thiazol-2-amine) and CuNO3 crystallized with 10 to form [Cu2(NO3)(13)2(MeCN)]NO3 (13 = dipyridyltetraazathiapentalene)

More than just tracking time: Complex measures of user engagement with an internet-based health promotion intervention

BACKGROUND: There has been a rise in internet-based health interventions without a concomitant focus on new methods to measure user engagement and its effect on outcomes. We describe current user tracking methods for internet-based health interventions and offer suggestions for improvement based on the design and pilot testing of healthMpowerment.org (HMP). METHODS: HMP is a multi-component online intervention for young Black men and transgender women who have sex with men (YBMSM/TW) to reduce risky sexual behaviors, promote healthy living and build social support. The intervention is non-directive, incorporates interactive features, and utilizes a point-based reward system. Fifteen YBMSM/TW (age 20-30) participated in a one-month pilot study to test the usability and efficacy of HMP. Engagement with the intervention was tracked using a customized data capture system and validated with Google Analytics. Usage was measured in time spent (total and across sections) and points earned. RESULTS: Average total time spent on HMP was five hours per person (range 0-13). Total time spent was correlated with total points earned and overall site satisfaction. CONCLUSION: Measuring engagement in internet-based interventions is crucial to determining efficacy. Multiple methods of tracking helped derive more comprehensive user profiles. Results highlighted the limitations of measures to capture user activity and the elusiveness of the concept of engagement

Frailty in Chronic Obstructive Pulmonary Disease and Risk of Exacerbations and Hospitalizations

Background: Frailty is a complex clinical syndrome associated with vulnerability to adverse health outcomes. While frailty is thought to be common in chronic obstructive pulmonary disease (COPD), the relationship between frailty and COPD-related outcomes such as risk of acute exacerbations of COPD (AE-COPD) and hospitalizations is unclear.Purpose: To examine the association between physical frailty and risk of acute exacerbations, hospitalizations, and mortality in patients with COPD.Methods: A longitudinal analysis of data from a cohort of 280 participants was performed. Baseline frailty measures included exhaustion, weakness, low activity, slowness, and undernutrition. Outcome measures included AE-COPD, hospitalizations, and mortality over 2 years. Negative binomial regression and Cox proportional hazard modeling were used.Results: Sixty-two percent of the study population met criteria for pre-frail and 23% were frail. In adjusted analyses, the frailty syndrome was not associated with COPD exacerbations. However, among the individual components of the frailty syndrome, weakness measured by handgrip strength was associated with increased risk of COPD exacerbations (IRR 1.46, 95% CI 1.09– 1.97). The frailty phenotype was not associated with all-cause hospitalizations but was associated with increased risk of non-COPD-related hospitalizations.Conclusion: This longitudinal cohort study shows that a high proportion of patients with COPD are pre-frail or frail. The frailty phenotype was associated with an increased risk of non-COPD hospitalizations but not with all-cause hospitalizations or COPD exacerbations. Among the individual frailty components, low handgrip strength was associated with increased risk of COPD exacerbations over a 2-year period. Measuring handgrip strength may identify COPD patients who could benefit from programs to reduce COPD exacerbations

Within- and between-host dynamics of producer and non-producer pathogens

For infections to be maintained in a population, pathogens must compete to colonise hosts and transmit between them. Within the host, much research has been conducted into pathogeni interactions, yet less is known about whether within-host interactions can affect between-host transmission. In this study, we use an experimental approach to investigate within-and-between host dynamics using the pathogen Pseudomonas aeruginosa and the host Caenorhabditis elegans. Within-host interactions often involve the production of goods, that are beneficial to all the pathogens in the local environment but susceptible to exploitation by non-producers. We exposed the nematode host to ‘producer’ and two ‘non-producer’ bacterial strains (specifically for siderophore production and quorum sensing), in single infections and coinfections, to investigate within-host colonisation. Subsequently, we introduced infected nematodes to pathogen-naive populations, to allow natural pathogen transmission between hosts. We find that producer pathogens are consistently better at colonising hosts and transmitting between them than non-producers during coinfection and single infection. Non-producers were poor at colonising hosts and between-host transmission, even when coinfecting with producers. Understanding pathogen dynamics across these multiple levels will ultimately help us to predict and control the spread of infections and contribute to explanations for the persistence of cooperative genotypes in natural populations

If you build it will they come? Addressing social isolation within a technology-based HIV intervention for young black men who have sex with men

The rate of HIV infections among young black men who have sex with men (YBMSM) continues to rise at an alarming pace. YBMSM are particularly vulnerable to social isolation and a lack of social support due to experiences with racism and homophobia, which may have implications for sexual risk behaviors. The purpose of this study was to explore perceptions of social isolation and sense of community among YBMSM, the need for and receptivity to social networking features designed to reduce social isolation and build community within an internet and mobile phone-based primary and secondary HIV prevention intervention for YBMSM and to identify strategies to develop these features. Focus groups were conducted with 22 YBMSM ages 20–30 at three sites in North Carolina. Data from the focus groups were thematically analyzed using NVivo. Feelings of social isolation and lack of a sense of community were strongly endorsed by participants with homophobia, lack of opportunities for social engagement, and a focus on sex rather than friendship in interpersonal relationships with other YBMSM cited as contributing factors. Participants were receptive to a social networking intervention designed to reduce social isolation and build community. Recommendations offered by participants to increase acceptability and usability of such features included: availability of information about healthy relationships, the ability to connect with other YBMSM and health care providers, and ensuring the site had ongoing facilitation by the study team as well as monitoring for inappropriate content. The development of a social networking feature of an HIV prevention intervention may present an opportunity to reduce social isolation, build community and reduce risky sexual behaviors among YBMSM. The findings from this study are being used to inform the development of a social networking feature for an existing internet and mobile phone-based primary and secondary HIV prevention intervention for YBMSM

HealthMpowerment.org: Building Community Through a Mobile-Optimized, Online Health Promotion Intervention

Both young Black men who have sex with men as well as young Black transgender women (YBMSM/TW) continue to experience a significant increase in HIV incidence. HealthMpowerment.org (HMP) is a mobile phone-optimized, online intervention for both YBMSM/TW to build community and facilitate supportive relationships

Putting Prevention in Their Pockets: Developing Mobile Phone-Based HIV Interventions for Black Men Who Have Sex with Men

Young black men who have sex with men (MSM) bear a disproportionate burden of HIV. Rapid expansion of mobile technologies, including smartphone applications (apps), provides a unique opportunity for outreach and tailored health messaging. We collected electronic daily journals and conducted surveys and focus groups with 22 black MSM (age 18–30) at three sites in North Carolina to inform the development of a mobile phone-based intervention. Qualitative data was analyzed thematically using NVivo. Half of the sample earned under $11,000 annually. All participants owned smartphones and had unlimited texting and many had unlimited data plans. Phones were integral to participants' lives and were a primary means of Internet access. Communication was primarily through text messaging and Internet (on-line chatting, social networking sites) rather than calls. Apps were used daily for entertainment, information, productivity, and social networking. Half of participants used their phones to find sex partners; over half used phones to find health information. For an HIV-related app, participants requested user-friendly content about test site locators, sexually transmitted diseases, symptom evaluation, drug and alcohol risk, safe sex, sexuality and relationships, gay-friendly health providers, and connection to other gay/HIV-positive men. For young black MSM in this qualitative study, mobile technologies were a widely used, acceptable means for HIV intervention. Future research is needed to measure patterns and preferences of mobile technology use among broader samples

Natural immunity to malaria preferentially targets the endothelial protein C receptor-binding regions of PfEMP1s

Antibody responses to variant surface antigens (VSAs) produced by the malaria parasite Plasmodium falciparum may contribute to age-related natural immunity to severe malaria. One VSA family, P. falciparum erythrocyte membrane protein-1 (PfEMP1), includes a subset of proteins that binds endothelial protein C receptor (EPCR) in human hosts and potentially disrupts the regulation of inflammatory responses, which may lead to the development of severe malaria. We probed peptide microarrays containing segments spanning five PfEMP1 EPCR-binding domain variants with sera from 10 Malian adults and 10 children to determine the differences between adult and pediatric immune responses. We defined serorecognized peptides and amino acid residues as those that elicited a significantly higher antibody response than malaria-naïve controls. We aimed to identify regions consistently serorecognized among adults but not among children across PfEMP1 variants, potentially indicating regions that drive the development of immunity to severe malaria. Adult sera consistently demonstrated broader and more intense serologic responses to constitutive PfEMP1 peptides than pediatric sera, including peptides in EPCR-binding domains. Both adults and children serorecognized a significantly higher proportion of EPCR-binding peptides than peptides that do not directly participate in receptor binding, indicating a preferential development of serologic responses at functional residues. Over the course of a single malaria transmission season, pediatric serological responses increased between the start and the peak of the season, but waned as the transmission season ended. IMPORTANCE Severe malaria and death related to malaria disproportionately affect sub-Saharan children under 5 years of age, commonly manifesting as cerebral malaria and/or severe malarial anemia. In contrast, adults in malaria-endemic regions tend to experience asymptomatic or mild disease. Our findings indicate that natural immunity to malaria targets specific regions within the EPCR-binding domain, particularly peptides containing EPCR-binding residues. Epitopes containing these residues may be promising targets for vaccines or therapeutics directed against severe malaria. Our approach provides insight into the development of natural immunity to a binding target linked to severe malaria by characterizing an "adult-like" response as recognizing a proportion of epitopes within the PfEMP1 protein, particularly regions that mediate EPCR binding. This "adult-like" response likely requires multiple years of malaria exposure, as increases in pediatric serologic response over a single malaria transmission season do not appear significant. </p

Informed consent for MRI and fMRI research: Analysis of a sample of Canadian consent documents

<p>Abstract</p> <p>Background</p> <p>Research ethics and the measures deployed to ensure ethical oversight of research (e.g., informed consent forms, ethics review) are vested with extremely important ethical and practical goals. Accordingly, these measures need to function effectively in real-world research and to follow high level standards.</p> <p>Methods</p> <p>We examined approved consent forms for Magnetic Resonance Imaging (MRI) and functional Magnetic Resonance Imaging (fMRI) studies approved by Canadian research ethics boards (REBs).</p> <p>Results</p> <p>We found evidence of variability in consent forms in matters of physical and psychological risk reporting. Approaches used to tackle the emerging issue of incidental findings exposed extensive variability between and within research sites.</p> <p>Conclusion</p> <p>The causes of variability in approved consent forms and studies need to be better understood. However, mounting evidence of administrative and practical hurdles within current ethics governance systems combined with potential sub-optimal provision of information to and protection of research subjects support other calls for more scrutiny of research ethics practices and applicable revisions.</p

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie