An interdisciplinary framework for measuring and supporting adherence in HIV prevention trials of ARV‐based vaginal rings

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138229/1/jia29158.pd

Sequential cavity method for computing free energy and surface pressure

We propose a new method for the problems of computing free energy and surface pressure for various statistical mechanics models on a lattice $\Z^d$. Our method is based on representing the free energy and surface pressure in terms of certain marginal probabilities in a suitably modified sublattice of $\Z^d$. Then recent deterministic algorithms for computing marginal probabilities are used to obtain numerical estimates of the quantities of interest. The method works under the assumption of Strong Spatial Mixing (SSP), which is a form of a correlation decay. We illustrate our method for the hard-core and monomer-dimer models, and improve several earlier estimates. For example we show that the exponent of the monomer-dimer coverings of $\Z^3$ belongs to the interval $[0.78595,0.78599]$, improving best previously known estimate of (approximately) $[0.7850,0.7862]$ obtained in \cite{FriedlandPeled},\cite{FriedlandKropLundowMarkstrom}. Moreover, we show that given a target additive error $\epsilon>0$, the computational effort of our method for these two models is $(1/\epsilon)^{O(1)}$ \emph{both} for free energy and surface pressure. In contrast, prior methods, such as transfer matrix method, require $\exp\big((1/\epsilon)^{O(1)}\big)$ computation effort.Comment: 33 pages, 4 figure

Re-Inventing Adherence: Toward a Patient-Centered Model of Care for Drug-Resistant Tuberculosis and HIV

BACKGROUND—Despite renewed focus on molecular tuberculosis (TB) diagnostics and new antimycobacterial agents, treatment outcomes for patients co-infected with drug-resistant TB and human immunodeficiency virus (HIV) remain dismal, in part due to lack of focus on medication adherence as part of a patient-centered continuum of care. OBJECTIVE—To review current barriers to drug-resistant TB-HIV treatment and propose an alternative model to conventional approaches to treatment support. DISCUSSION—Current national TB control programs rely heavily on directly observed therapy (DOT) as the centerpiece of treatment delivery and adherence support. Medication adherence and care for drug-resistant TB-HIV could be improved by fully implementing team-based patient-centered care, empowering patients through counseling and support, maintaining a rights-based approach while acknowledging the responsibility of health care systems in providing comprehensive care, and prioritizing critical research gaps. CONCLUSION—It is time to re-invent our understanding of adherence in drug-resistant TB and HIV by focusing attention on the complex clinical, behavioral, social, and structural needs of affected patients and communities

Low-Energy Signals from Kinetic Mixing with a Warped Abelian Hidden Sector

We investigate the detailed phenomenology of a light Abelian hidden sector in the Randall-Sundrum framework. Relative to other works with light hidden sectors, the main new feature is a tower of hidden Kaluza-Klein vectors that kinetically mix with the Standard Model photon and Z. We investigate the decay properties of the hidden sector fields in some detail, and develop an approach for calculating processes initiated on the ultraviolet brane of a warped space with large injection momentum relative to the infrared scale. Using these results, we determine the detailed bounds on the light warped hidden sector from precision electroweak measurements and low-energy experiments. We find viable regions of parameter space that lead to significant production rates for several of the hidden Kaluza-Klein vectors in meson factories and fixed-target experiments. This offers the possibility of exploring the structure of an extra spacetime dimension with lower-energy probes.Comment: (1+32) Pages, 13 Figures. v2: JHEP version (minor modifications, results unchanged

High-dimensional analysis of the aging immune system: verification of age-associated differences in immune signaling responses in healthy donors.

BACKGROUND Single-cell network profiling (SCNP) is a multiparametric flow cytometry-based approach that simultaneously measures evoked signaling in multiple cell subsets. Previously, using the SCNP approach, age-associated immune signaling responses were identified in a cohort of 60 healthy donors. METHODS In the current study, a high-dimensional analysis of intracellular signaling was performed by measuring 24 signaling nodes in 7 distinct immune cell subsets within PBMCs in an independent cohort of 174 healthy donors [144 elderly (>65 yrs); 30 young (25-40 yrs)]. RESULTS Associations between age and 9 immune signaling responses identified in the previously published 60 donor cohort were confirmed in the current study. Furthermore, within the current study cohort, 48 additional immune signaling responses differed significantly between young and elderly donors. These associations spanned all profiled modulators and immune cell subsets. CONCLUSIONS These results demonstrate that SCNP, a systems-based approach, can capture the complexity of the cellular mechanisms underlying immunological aging. Further, the confirmation of age associations in an independent donor cohort supports the use of SCNP as a tool for identifying reproducible predictive biomarkers in areas such as vaccine response and response to cancer immunotherapies

Safety and efficacy of hydroxychloroquine as prophylactic against COVID-19 in healthcare workers: a meta-analysis of randomised clinical trials

OBJECTIVE: We studied the safety and efficacy of hydroxychloroquine (HCQ) as pre-exposure prophylaxis for COVID-19 in healthcare workers (HCWs), using a meta-analysis of randomised controlled trials (RCTs). DATA SOURCES: PubMed and EMBASE databases were searched to identify randomised trials studying HCQ. STUDY SELECTION: Ten RCTs were identified (n=5079 participants). DATA EXTRACTION AND SYNTHESIS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used in this systematic review and meta-analysis between HCQ and placebo using a Bayesian random-effects model. A pre-hoc statistical analysis plan was written. MAIN OUTCOMES: The primary efficacy outcome was PCR-confirmed SARS-CoV-2 infection and the primary safety outcome was incidence of adverse events. The secondary outcome included clinically suspected SARS-CoV-2 infection. RESULTS: Compared with placebo, HCWs randomised to HCQ had no significant difference in PCR-confirmed SARS-CoV-2 infection (OR 0.92, 95% credible interval (CI): 0.58, 1.37) or clinically suspected SARS-CoV-2 infection (OR 0.78, 95% CI: 0.57, 1.10), but significant difference in adverse events (OR 1.35, 95% CI: 1.03, 1.73). CONCLUSIONS AND RELEVANCE: Our meta-analysis of 10 RCTs investigating the safety and efficacy of HCQ as pre-exposure prophylaxis in HCWs found that compared with placebo, HCQ does not significantly reduce the risk of confirmed or clinically suspected SARS-CoV-2 infection, while HCQ significantly increases adverse events. PROSPERO REGISTRATION NUMBER: CRD42021285093

Seasonal Phytoplankton Blooms in the North Atlantic Linked to the Overwintering Strategies of Copepods

The North Atlantic Ocean contains diverse patterns of seasonal phytoplankton blooms with distinct internal dynamics. We analyzed blooms using remotely-sensed chlorophyll a concentration data and change point statistics. The first bloom of the year began during spring at low latitudes and later in summer at higher latitudes. In regions where spring blooms occurred at high frequency (i. e., proportion of years that a bloom was detected), there was a negative correlation between bloom timing and duration, indicating that early blooms last longer. In much of the Northeast Atlantic, bloom development extended over multiple seasons resulting in peak chlorophyll concentrations in summer. Spring bloom start day was found to be positively correlated with a spring phenology index and showed both positive and negative correlations to sea surface temperature and the North Atlantic Oscillation in different regions. Based on the characteristics of spring and summer blooms, the North Atlantic can be classified into two regions: a seasonal bloom region, with a well-defined bloom limited to a single season; and a multi-seasonal bloom region, with blooms extending over multiple seasons. These regions differed in the correlation between bloom start and duration with only the seasonal bloom region showing a significant, negative correlation. We tested the hypothesis that the near-surface springtime distribution of copepods that undergo diapause (Calanus finmarchicus, C. helgolandicus, C. glacialis, and C. hyperboreus) may contribute to the contrast in bloom development between the two regions. Peak near-surface spring abundance of the late stages of these Calanoid copepods was generally associated with areas having a well-defined seasonal bloom, implying a link between bloom shape and their abundance. We suggest that either grazing is a factor in shaping the seasonal bloom or bloom shape determines whether a habitat is conducive to diapause, while recognizing that both factors can re-enforce each other

Low-Energy Probes of a Warped Extra Dimension

We investigate a natural realization of a light Abelian hidden sector in an extended Randall-Sundrum (RS) model. In addition to the usual RS bulk we consider a second warped space containing a bulk U(1)_x gauge theory with a characteristic IR scale of order a GeV. This Abelian hidden sector can couple to the standard model via gauge kinetic mixing on a common UV brane. We show that if such a coupling induces significant mixing between the lightest U(1)_x gauge mode and the standard model photon and Z, it can also induce significant mixing with the heavier U(1)_x Kaluza-Klein (KK) modes. As a result it might be possible to probe several KK modes in upcoming fixed-target experiments and meson factories, thereby offering a new way to investigate the structure of an extra spacetime dimension.Comment: 26 pages, 1 figure, added references, corrected minor typos, same as journal versio

Seasonal Phytoplankton Blooms in the North Atlantic Linked to the Overwintering Strategies of Copepods

The North Atlantic Ocean contains diverse patterns of seasonal phytoplankton blooms with distinct internal dynamics. We analyzed blooms using remotely-sensed chlorophyll a concentration data and change point statistics. The first bloom of the year began during spring at low latitudes and later in summer at higher latitudes. In regions where spring blooms occurred at high frequency (i. e., proportion of years that a bloom was detected), there was a negative correlation between bloom timing and duration, indicating that early blooms last longer. In much of the Northeast Atlantic, bloom development extended over multiple seasons resulting in peak chlorophyll concentrations in summer. Spring bloom start day was found to be positively correlated with a spring phenology index and showed both positive and negative correlations to sea surface temperature and the North Atlantic Oscillation in different regions. Based on the characteristics of spring and summer blooms, the North Atlantic can be classified into two regions: a seasonal bloom region, with a well-defined bloom limited to a single season; and a multi-seasonal bloom region, with blooms extending over multiple seasons. These regions differed in the correlation between bloom start and duration with only the seasonal bloom region showing a significant, negative correlation. We tested the hypothesis that the near-surface springtime distribution of copepods that undergo diapause (Calanus finmarchicus, C. helgolandicus, C. glacialis, and C. hyperboreus) may contribute to the contrast in bloom development between the two regions. Peak near-surface spring abundance of the late stages of these Calanoid copepods was generally associated with areas having a well-defined seasonal bloom, implying a link between bloom shape and their abundance. We suggest that either grazing is a factor in shaping the seasonal bloom or bloom shape determines whether a habitat is conducive to diapause, while recognizing that both factors can re-enforce each other

Description and evaluation of an EBM curriculum using a block rotation

BACKGROUND: While previous authors have emphasized the importance of integrating and reinforcing evidence-based medicine (EBM) skills in residency, there are few published examples of such curricula. We designed an EBM curriculum to train family practice interns in essential EBM skills for information mastery using clinical questions generated by the family practice inpatient service. We sought to evaluate the impact of this curriculum on interns, residents, and faculty. METHODS: Interns (n = 13) were asked to self-assess their level of confidence in basic EBM skills before and after their 2-week EBM rotation. Residents (n = 21) and faculty (n = 12) were asked to assess how often the answers provided by the EBM intern to the inpatient service changed medical care. In addition, residents were asked to report how often they used their EBM skills and how often EBM concepts and tools were used in teaching by senior residents and faculty. Faculty were asked if the EBM curriculum had increased their use of EBM in practice and in teaching. RESULTS: Interns significantly increased their confidence over the course of the rotation. Residents and faculty felt that the answers provided by the EBM intern provided useful information and led to changes in patient care. Faculty reported incorporating EBM into their teaching (92%) and practice (75%). Residents reported applying the EBM skills they learned to patient care (86%) and that these skills were reinforced in the teaching they received outside of the rotation (81%). All residents and 11 of 12 faculty felt that the EBM curriculum had improved patient care. CONCLUSIONS: To our knowledge, this is the first published EBM curriculum using an individual block rotation format. As such, it may provide an alternative model for teaching and incorporating EBM into a residency program