Mary Clifford Webster Darling Correspondence

Entries include some correct biographical information typed by the Maine State Library and handwritten correspondence on a Fredericka Manor card and plain paper stationery

Vitamin A and zinc supplementation among pregnant women to prevent placental malaria: a randomized, double-blind, placebo-controlled trial in Tanzania

BACKGROUND: Malaria causes nearly 200 million clinical cases and approximately half a million deaths each year, primarily in sub-Saharan Africa.1 The risk of malaria increases during pregnancy,2 a period during which its prevention is especially important. Not only do pregnant women experience greater severity of illness compared with nonpregnant women,2 but studies have shown strong associations between prenatal malaria and maternal anemia,2 fetal loss, low birthweight, and infant mortality.2 Improving preventive measures that specifically target malaria in pregnancy is a global health priority.3 METHODS: Study design and participants. This randomized, doubleblind, placebo-controlled trial was implemented at 8 antenatal care clinics in the urban Temeke and Ilala districts of Dar es Salaam, Tanzania. The trial was registered RESULTS: A total of 2,500 screened participants were enrolled in the trial. The trial profile is shown in Figure 1. It was not possible to collect placentas from 875 participants for the following reasons: miscarriages (fetal loss before 28 weeks of gestation) (N = 234), delivery outside of Dar es Salaam or at a non-study hospital (N = 577), or withdrawal from the study (N = 34). Of the remaining 1,589 women, 1,404 placental samples were obtained (88%); histology results were available for 1,361 participants. PCR results were available for 1,158 participants, and 1,404 participants had either histology or PCR results available. CONCLUSION: This study is the first to examine the impact of vitamin A and zinc supplementation starting in early pregnancy on placental malaria. We observed that supplementation with 25 mg zinc per day from the first trimester until delivery was associated with a 36% (95% CI = 9–56%) reduced risk of histopathology-positive placental infection, but not PCRpositive infection. Vitamin A supplementation had no impact on placental malaria, but was associated with an increased risk for severe anemia

Attachment as a partial mediator of the relationship between emotional abuse and schizotypy

Developmental theories highlight the salience of attachment theory in explaining vulnerability towards psychosis. At the same time there is increasing recognition that psychosis is associated with childhood trauma variables. This study explored the interaction between attachment and several trauma variables in relation to schizotypy levels in a non-clinical sample. 283 non-clinical participants completed online measures of schizotypy, attachment, childhood abuse and neglect. When five types of abuse/neglect were entered into a linear regression analysis emotional abuse was the sole independent predictor of schizotypy. Age, attachment anxiety and avoidance were independent predictors after the effects of emotional abuse were controlled for. The overall model was significant, explaining 34% of the variation in schizotypy. Moderation analysis indicated that the effect of emotional abuse was not conditional upon attachment. Parallel mediation analysis indicated small but significant indirect effects of emotional abuse on schizotypy through attachment avoidance (13%) and attachment anxiety (8%). We conclude that emotional abuse contributes to vulnerability towards psychosis both directly and indirectly through attachment insecurity

Improved Survival after Heart Failure: A Community-based Perspective

Background: Heart failure is a highly prevalent, morbid, and costly disease with a poor long-term prognosis. Evidence-based therapies utilized over the past 2 decades hold the promise of improved outcomes, yet few contemporary studies have examined survival trends in patients with acute heart failure. Objectives: The primary objective of this population-based study was to describe trends in short and long-term survival in patients hospitalized with acute decompensated heart failure (ADHF). A secondary objective was to examine patient characteristics associated with decreased long-term survival. Methods and Results: We reviewed the medical records of 9,748 patients hospitalized with ADHF at all 11 medical centers in central Massachusetts during 1995, 2000, 2002, and 2004. Patients hospitalized with ADHF were more likely to be elderly and to have been diagnosed with multiple comorbidities in 2004 compared with 1995. Over this period, survival was significantly improved in-hospital, and at 1, 2, and 5 years post-discharge. Five-year survival rates increased from 20% in 1995 to 28% in 2004. Although survival improved substantially over time, older patients and patients with chronic kidney disease, chronic obstructive pulmonary disease, anemia, low body mass index, and low blood pressures had consistently lower post-discharge survival rates than patients without these comorbidities. Conclusion: Between 1995 and 2004, patients hospitalized with ADHF have become older and increasingly comorbid. Although there has been a significant improvement in survival among these patients, their long-term prognosis remains poor, as fewer than 1 in 3 patients hospitalized with ADHF in 2004 survived more than 5 years

Thyroxine-thyroid hormone receptor interactions

ABSTRACTThyroid hormone (TH) actions are mediated by nuclear receptors (TRs α and β) that bind triiodothyronine (T3, 3,5,3′-triiodo-l-thyronine) with high affinity, and its precursor thyroxine (T4, 3,5,3′,5′-tetraiodo-l-thyronine) with lower affinity. T4 contains a bulky 5′ iodine group absent from T3. Because T3 is buried in the core of the ligand binding domain (LBD), we have predicted that TH analogues with 5′ substituents should fit poorly into the ligand binding pocket and perhaps behave as antagonists. We therefore examined how T4 affects TR activity and conformation. We obtained several lines of evidence (ligand dissociation kinetics, migration on hydrophobic interaction columns, and non-denaturing gels) that TR-T4 complexes adopt a conformation that differs from TR-T3 complexes in solution. Nonetheless, T4 behaves as an agonist in vitro (in effects on coregulator and DNA binding) and in cells, when conversion to T3 does not contribute to agonist activity. We determined x-ray crystal structures of the TRβ LBD in complex with T3 and T4 at 2.5-Å and 3.1-Å resolution. Comparison of the structures reveals that TRβ accommodates T4 through subtle alterations in the loop connecting helices 11 and 12 and amino acid side chains in the pocket, which, together, enlarge a niche that permits helix 12 to pack over the 5′ iodine and complete the coactivator binding surface. While T3 is the major active TH, our results suggest that T4 could activate nuclear TRs at appropriate concentrations. The ability of TR to adapt to the 5′ extension should be considered in TR ligand design

Bermuda 2.0: Reflections from Santa Cruz

In February 1996, the genome community met in Bermuda to formulate principles for circulating genomic data. Although it is now 20 years since the Bermuda Principles were formulated, they continue to play a central role in shaping genomic and data-sharing practices. However, since 1996, “openness” has become an increasingly complex issue. This commentary seeks to articulate three core challenges data-sharing faces today

Monitoring of methane in groundwater from the Vale of Pickering, UK: temporal variability and source discrimination

Groundwater abstracted from aquifers in the Vale of Pickering, North Yorkshire, UK and monitored over the period 2015–2022, shows evidence of variable but commonly high concentrations of dissolved CH4. Sampled groundwater from the Jurassic organic-rich Kimmeridge Clay Formation (boreholes up to 180 m depth) has concentrations up to 57 mg/L, and concentrations up to 59 mg/L are found in groundwater from underlying confined Corallian Group limestone (borehole depths 50–227 m). The high concentrations are mainly from boreholes in the central parts of the vale. Small concentrations of ethane (C2H6, up to 800 μg/L) have been found in the Kimmeridge Clay and confined Corallian groundwaters, and of propane (C3H8, up to 160 μg/L) in deeper boreholes (110–180 m) from these formations. The concentrations are typically higher in groundwater from the deeper boreholes and vary with hydrostatic pressure, reflecting the pressure control on CH4 solubility. The occurrences contrast with groundwater from shallow Quaternary superficial deposits which have low CH4 concentrations (up to 0.39 mg/L), and with the unconfined and semi-confined sections of the Corallian aquifer (up to 0.7 mg/L) around the margins of the vale. Groundwater from the Quaternary, Kimmeridge Clay formations and to a small extent the confined Corallian aquifer, supports local private-water supplies, that from the peripheral unconfined sections of Corallian also supports public supply for towns and villages across the region. Dissolved methane/ethane (C1/C2) ratios and stable-isotopic compositions (δ13C-CH4, δ2H-CH4 and δ13C-CO2) suggest that the high-CH4 groundwater from both the Kimmeridge Clay and confined Corallian formations derives overwhelmingly from biogenic reactions, the methanogenesis pathway by CO2 reduction. A small minority of groundwater samples shows a more enriched δ13C-CH4 composition (−50 to −44 ‰) which has been interpreted as due to anaerobic or aerobic methylotrophic oxidation in situ or post-sampling oxidation, rather than derivation by a thermogenic route. Few of the existing groundwater sites are proximal to abandoned or disused conventional hydrocarbon wells that exist in the region, and little evidence has been found for an influence on groundwater dissolved gases from these sites. The Vale of Pickering has also been under recent consideration for development of an unconventional hydrocarbon (shale-gas) resource. In this context, the monitoring of dissolved gases has been an important step in establishing the high-CH4 baseline of groundwaters from Jurassic deposits in the region and in apportioning their sources and mechanisms of genesis

Effectiveness of Simeprevir Plus Sofosbuvir, With or Without Ribavirin, in Real-World Patients With HCV Genotype 1 Infection

The interferon-free regimen of simeprevir plus sofosbuvir was recommended by professional guidelines for certain patients with hepatitis C virus (HCV) genotype 1 infection based on the findings of a phase 2 trial. We aimed to evaluate the safety and efficacy of this regimen in clinical practice settings in North America

2nd Annual Faculty Research & Innovation Day Program

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