Warkite (IMA 2013-129) is a new Sc-rich ultrarefractory mineral in the rhönite group of the sapphirine supergroup. It has a P1¯ aenigmatite-type structure with a = 10.367 Å, b = 10.756 Å, ...c = 8.895 Å, α = 106°, β = 96°, γ = 125°, and Z = 2, and general formula of Ca2(Sc,Ti,Al,Mg,Zr)6Al6O20. Warkite occurs as micrometer-sized crystals in eleven ultrarefractory Ca,Al-rich inclusions (UR CAIs) from the CM, CV, CO, and CH chondrites. In the CM, CO, and CV CAIs, warkite in the cores coexists with a Ti-rich oxide, either perovskite or kangite; the cores are generally mantled and rimmed by davisite and/or Sc-diopside. In the CH CAIs and one CO CAI, warkite in the cores coexists with perovskite and grossite; the cores are mantled by grossite ± gehlenite, and rimmed by low-Sc, Al-diopside. Therefore, there are two basic families of warkite-bearing inclusions, those containing Sc-rich clinopyroxene but no grossite and those containing grossite but no Sc-rich clinopyroxene. Scandian clinopyroxene in warkite-bearing CAIs generally formed by the reaction of warkite, which supplied most or all of the Sc, Ti, and Al, and a nebular gas that supplied much of the Ca and O and virtually all of the Mg and Si. The presence of Sc-rich clinopyroxenes may reflect exposure of some warkite-bearing CAIs to a dust-rich environment, which would enhance partial pressures of Si-, Mg-, and Ca-bearing species in the vapor and make it oxidizing relative to a dust-poor gas. Warkite in grossite-bearing inclusions is generally Ti3+-enriched relative to those in davisite-bearing inclusions, consistent with their formation in relatively dust-poor, more-reducing environments. Warkite compositions are sensitive to the presence or absence of spinel, melilite, Sc-rich clinopyroxenes, and grossite. Compositional variations of perovskite and warkite grains indicate a connection but, except for late-stage Fe exchange, they did not equilibrate with each other. The presence of at least two trends in Y-Sc among perovskites without corresponding trends in warkite suggests that at least some perovskite formed separately.
Warkite-bearing CAIs from CM2s and CO3.0s are uniformly 16O-rich (Δ17O ∼ −23‰), whereas those from metamorphosed COs and CVs are isotopically heterogeneous: warkite, kangite, perovskite, melilite, and davisite are 16O-depleted to various degrees (Δ17O range from −22 to −2‰) relative to hibonite, spinel, and forsterite, all having 16O-rich compositions (Δ17O ∼ − 25 to −20‰). We infer that warkite-bearing CAIs originated in an 16O-rich nebular gas. Subsequently, CAIs from metamorphosed CVs and COs experienced O-isotope exchange with an 16O-depleted external reservoir, most likely aqueous fluids on the CV and CO chondrite parent asteroids; however, O-isotope exchange in the solar nebula cannot be excluded.
Abstract Background Pulmonary Exacerbations (PEx) are associated with increased morbidity and mortality in individuals with CF. PEx management practices vary widely, and optimization through ...interventional trials could potentially improve outcomes. The object of this analysis was to evaluate current physician treatment practices and patient outcomes for PEx. Methods The Standardized Treatment of Pulmonary Exacerbations (STOP) observational study enrolled 220 participants ≥ 12 years old admitted to the hospital for PEx at 11 U.S. CF centers. Spirometry and daily symptom scores were collected during the study. Physicians were surveyed on treatment goals and their management practices were observed. Treatment outcomes were compared to stated goals. Results The mean (SD) duration of IV antibiotic treatment was 15.9 (6.0) days. Those individuals with more severe lung disease (< 50% FEV1 ) were treated nearly two days longer than those with > 50% FEV1 . Physician-reported FEV1 improvement goals were 10% (95% CI: 5%, 14%) lower for patients with 6-month baseline FEV1 ≤ 50% predicted compared with those with 6-month baseline FEV1 > 50% predicted. There were clinically and statistically significant improvements in symptoms from the start of IV antibiotic treatment to the end of IV antibiotic treatment and 28 days after the start of treatment. The mean absolute increase in FEV1 from admission was 9% predicted at end of IV antibiotic treatment, and 7% predicted at day 28. Only 39% fully recovered lost lung function, and only 65% recovered at least 90% of lost lung function. Treatment was deemed successful by 84% of clinicians, although 6-month baseline FEV1 was only recovered in 39% of PEx. Conclusions In this prospective observational study of PEx, treatment regimens and durations showed substantial variation. A significant proportion of patients did not reach physician's treatment goals, yet treatment was deemed successful.
Monipite (IMA 2007-033), MoNiP, is a new phosphide mineral that occurs as one 1 × 2 µm crystal in a Type B1 Ca-Al-rich inclusion (CAI) ACM-2 from the Allende CV3 carbonaceous chondrite. It has an ...empirical formula of (Mo0.84Fe0.06Co0.04Rh0.03)(Ni0.89Ru0.09)P, and a P6 2m Fe2P type structure with a = 5.861, c = 3.704 Å, V = 110.19 Å3, and Z = 3. The calculated density using our measured composition is 8.27 g/cm3, making monipite the densest known mineral phosphide. Monipite probably either crystallized from an immiscible P-rich melt that had exsolved from an Fe-Ni-enriched alloy melt that formed during melting of the host CAI or it exsolved from a solidified alloy. Most of the original phosphide in the type occurrence was later altered to apatite and Mo-oxides, leaving only a small residual grain. Monipite occurs within an opaque assemblage included in melilite that contains kamiokite (Fe2Mo3O8), tugarinovite (MoO2), and a Nb-rich oxide (Nb,V,Fe)O2, none of which has previously been reported in meteorites, together with apatite, awaruite (Ni2Fe), and vanadian magnetite.
In the classical form of α₁-antitrypsin (AT) deficiency, a point mutation in AT alters the folding of a liver-derived secretory glycoprotein and renders it aggregation-prone. In addition to decreased ...serum concentrations of AT, the disorder is characterized by accumulation of the mutant α1-antitrypsin Z (ATZ) variant inside cells, causing hepatic fibrosis and/or carcinogenesis by a gain-of-toxic function mechanism. The proteasomal and autophagic pathways are known to mediate degradation of ATZ. Here we show that the autophagy-enhancing drug carbamazepine (CBZ) decreased the hepatic load of ATZ and hepatic fibrosis in a mouse model of AT deficiency-associated liver disease. These results provide a basis for testing CBZ, which has an extensive clinical safety profile, in patients with AT deficiency and also provide a proof of principle for therapeutic use of autophagy enhancers.
Correcting a Liver Problem
The classical form of α
1
-antitrypsin (AT) deficiency is caused by a point mutation that alters the folding and causes intracellular aggregation of AT—an abundant ...liver-derived plasma glycoprotein. AT deficiency is the most common genetic cause of liver disease in childhood and can also lead to cirrhosis and/or hepatocellular carcinoma in adulthood. Carbamazepine is a drug known to be well tolerated in humans that enhances the intracellular degradation process known as autophagy. Now,
Hidvegi
et al.
(p.
229
, published online June 3; see the Perspective by
Sifers
) show that carbamazepine can reduce the severity of liver disease in a mouse model of AT deficiency by enhancing the degradation of misfolded accumulated AT.
A mouse model of a human liver disease can be treated using a drug known to be well tolerated.
In the classical form of α
1
-antitrypsin (AT) deficiency, a point mutation in AT alters the folding of a liver-derived secretory glycoprotein and renders it aggregation-prone. In addition to decreased serum concentrations of AT, the disorder is characterized by accumulation of the mutant α1-antitrypsin Z (ATZ) variant inside cells, causing hepatic fibrosis and/or carcinogenesis by a gain–of–toxic function mechanism. The proteasomal and autophagic pathways are known to mediate degradation of ATZ. Here we show that the autophagy-enhancing drug carbamazepine (CBZ) decreased the hepatic load of ATZ and hepatic fibrosis in a mouse model of AT deficiency–associated liver disease. These results provide a basis for testing CBZ, which has an extensive clinical safety profile, in patients with AT deficiency and also provide a proof of principle for therapeutic use of autophagy enhancers.
Research on canopy arthropods has progressed from species inventories to the study of their interactions and networks, enhancing our understanding of how hyper-diverse communities are maintained. ...Previous studies often focused on sampling individual tree species, individual trees or their parts. We argue that such selective sampling is not ideal when analyzing interaction network structure, and may lead to erroneous conclusions. We developed practical and reproducible sampling guidelines for the plot-based analysis of arthropod interaction networks in forest canopies. Our sampling protocol focused on insect herbivores (leaf-chewing insect larvae, miners and gallers) and non-flying invertebrate predators (spiders and ants). We quantitatively sampled the focal arthropods from felled trees, or from trees accessed by canopy cranes or cherry pickers in 53 0.1 ha forest plots in five biogeographic regions, comprising 6,280 trees in total. All three methods required a similar sampling effort and provided good foliage accessibility. Furthermore, we compared interaction networks derived from plot-based data to interaction networks derived from simulated non-plot-based data focusing either on common tree species or a representative selection of tree families. All types of non-plot-based data showed highly biased network structure towards higher connectance, higher web asymmetry, and higher nestedness temperature when compared with plot-based data. Furthermore, some types of non-plot-based data showed biased diversity of the associated herbivore species and specificity of their interactions. Plot-based sampling thus appears to be the most rigorous approach for reconstructing realistic, quantitative plant-arthropod interaction networks that are comparable across sites and regions. Studies of plant interactions have greatly benefited from a plot-based approach and we argue that studies of arthropod interactions would benefit in the same way. We conclude that plot-based studies on canopy arthropods would yield important insights into the processes of interaction network assembly and dynamics, which could be maximised via a coordinated network of plot-based study sites.
Comprehensive sexuality education (CSE) is seen as a key instrument through which to affect behaviour and improve sexual and reproductive health (SRH) outcomes amongst adolescents. However, few ...studies have to date evaluated key SRH outcomes following exposure to CSE within a school setting. This study estimates the association between CSE and HIV testing and HIV testing self-efficacy amongst HIV positive adolescent girls. Data were collected from a cross-sectional survey administered in four high HIV prevalence districts . Independent variables included exposure to CSE, with outcome variables measuring uptake of HIV testing in the 12 months preceding the survey, and HIV testing self-efficacy. The sample comprised 505 HIV positive adolescent girls aged 12-19. . Attending CSE was associated with both; being more confident to get an HIV test (AOR: 2.44, 95% CI: 1.47-4.06, p < 0.001) and having ever tested for HIV (AOR: 2.15, 95% CI: 1.39-3.33, p < 0.001) while controlling for numerous variables. Results suggest CSE can play an important role in not only affecting HIV-related behaviours themselves, but also critical factors that affect HIV behaviours, including self-efficacy.
Abstract Background The Standardized Treatment of Pulmonary Exacerbations (STOP) program has the intent of defining best practices in the treatment of pulmonary exacerbations (PEx) in patients with ...cystic fibrosis (CF). The objective of this analysis was to describe the clinical presentations of patients admitted for intravenous (IV) antibiotics and enrolled in a prospective observational PEx study as well as to understand physician treatment goals at the start of the intervention. Methods We enrolled adolescents and adults admitted to the hospital for a PEx treated with IV antibiotics. We recorded patient and PEx characteristics at the time of enrollment. We surveyed treating physicians on treatment goals as well as their willingness to enroll patients in various study designs. Additional demographic and clinical data were obtained from the CF Foundation Patient Registry. Results Of 220 patients enrolled, 56% were female, 19% were adolescents, and 71% were infected with P. aeruginosa . The mean (SD) FEV1 at enrollment was 51.1 (21.6)% predicted. Most patients (85%) experienced symptoms for ≥ 7 days before admission, 43% had received IV antibiotics within the previous 6 months, and 48% received oral and/or inhaled antibiotics prior to IV antibiotic initiation. Forty percent had ≥ 10% FEV1 decrease from their best value recorded in the previous 6 months, but for 20% of patients, their enrollment FEV1 was their best FEV1 recorded within the previous 6 months. Physicians reported that their primary treatment objectives were lung function recovery (53%) and improvement of symptoms (47%) of PEx. Most physicians stated they would enroll patients in studies involving 10-day (72%) or 14-day (87%), but not 7-day (29%), treatment regimens. Conclusions Based on the results of this study, prospective studies are feasible and physician willingness for interventional studies of PEx exists. Results of this observational study will help design future PEx trials.
•The high prevalence of STIs provides compelling evidence for enhanced surveillance for STI control.•Prevalence of curable STIs was higher in the younger age groups among whom a peak in HIV incidence ...occurs.•The association between STIs and HIV, HIV viral load ≥400 copies per mL contributes to sustaining the STI and HIV epidemics.•STIs threaten the goal of achieving HIV epidemic control in this high HIV burden region.
Sexually transmitted infections (STIs) and Human immunodeficiency virus (HIV) share a complex bidirectional relationship, however, population prevalence and the association between the presence of STIs and HIV in a high HIV burden district in KwaZulu-Natal, South Africa is not known.
A total of 9812 participants aged 15–49 years were enrolled in a cross-sectional population-based household survey. Participants completed a structured questionnaire and provided first-pass urine (males) or self-collected vulvo-vaginal swabs (females) for the detection of STIs.
Prevalence of herpes simplex virus type-2 (HSV-2) was 57.8%, syphilis was 1.6%, Neisseria gonorrhoeae was 2.8%, Chlamydia trachomatis was 7.1%, Trichomonas vaginalis was 9.0%, Mycoplasma genitalium was 5.5% and HIV was 36.3%. HIV positive status was associated with an increased probability of having M. genitalium (aPR = 1.49, 95% CI 1.02–2.19) among males and syphilis (aPR = 2.54, 95% CI 1.32–4.86), N. gonorrhoeae (aPR = 2.39, 95% CI 1.62–3.52), T. vaginalis (aPR = 1.70, 95% CI 1.43–2.01) and M. genitalium (aPR = 1.60, 95% CI 1.15–2.22) among females. HIV viral load ≥400 copies per mL was associated with an increased probability of N. gonorrhoeae (aPR = 1.91, 95% CI 1.36–2.70), C. trachomatis (aPR = 1.52, 95% CI 1.12–2.05) and M. genitalium (aPR = 1.83, 95% CI 1.27–2.63).
The high prevalence of STIs and the association between STIs and HIV, and HIV viral load underscores the public health implications of sustained transmission risk of STIs and HIV. These findings highlight the urgent need for expanding STI surveillance and implementing interventions to monitor and reduce the STI burden.
HIV incidence among adolescent girls and young women (AGYW) remains high, with their male partners a prominent factor in sustaining these elevated rates. Partnership characteristics remain important ...metrics for determining HIV risk, with evidence indicating that AGYW engaged in transactional and age-disparate relationships face greater HIV exposure. This study examines the risk posed to AGYW in a relationship with a "Blesser", defined as male who provides his female partner with their material needs or desires in exchange for a sexual relationship, an age-disparate (5 or more years older) partner, and the potential compounded risk of being a relationship with a partner or partners who are considered both a "Blesser" and age-disparate.
A cross -sectional household based representative sample of AGYW (aged between 12-24 years) were enrolled in the study (n = 18 926) from the districts of City of Johannesburg and Ekurhuleni in the Gauteng province and the Districts of eThekwini and uMgungundlovu in the province of KwaZulu-Natal (KZN) in South Africa between March 13, 2017 to June 22, 2018. Participants completed a structured questionnaire and provided finger-prick blood samples for laboratory measurements. Our analysis used descriptive statistics and multiple binary logistic regressions accounting for survey weights, clustering and stratification.
The median age of the sample was 21 years old (Interquartile range: 19-23) and nearly three quarters (73.7%) were currently attending school. Whilst all relationships exposed AGYW to potential HIV risk, multiple binary logistic regression analysis revealed that AGYW in a relationship with both a Blesser and an age-disparate partner were more likely to be HIV positive (AOR: 3.12, 95% CI: 1.76-5.53, p < 0.001), diagnosed with an STI (AOR: 4.60, 95% CI: 2.99-7.08, p < 0.001), had 2 or more sexual partners in the previous 12 months (AOR: 6.37, 95% CI: 3.85-10.54, p < 0.001), engaged in sexual activity at age 15 or younger (AOR: 3.67, 95% CI: 2.36-5.69, p < 0.001) and more likely to have ever been pregnant (AOR: 2.60, 95% CI: 1.24-5.45, p < 0.05) than those not in a relationship with either a Blesser or age-disparate partner.
Different relationships present different HIV risk to AGYW. AGYW who had engaged in relationships with both a Blesser and an age-disparate partner were at greater HIV risk when examined against these relationships independent of one another. The data reveals the compounded HIV risk of being in both a transactional and age-disparate relationship.
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