NanTroSEIZE Stage 1 expeditions: introduction and synthesis of key results

Integrated Ocean Drilling Program Expeditions 314, 315, and 316 were carried out as a unified program of drilling collectively known as Stage 1 of the Nankai Trough Seismogenic Zone Experiment, a multistage complex drilling project. A transect of eight sites was selected for riserless drilling to target the frontal thrust region, midslope megasplay fault region, and Kumano forearc basin region. Two of these sites are preparatory pilot holes for planned deep riser drilling operations, whereas the others targeted fault zone material in the shallow, presumed aseismic zone. Expedition 314 was dedicated to in situ measurement of physical properties and borehole imaging through logging while drilling in holes dedicated to that purpose. Expedition 315 was devoted to core sampling and downhole temperature measurements at one site in the megasplay region and one site in the forearc basin. Expedition 316 targeted the frontal and out-of-sequence megasplay fault region in the mid-slope environment. Results on accretionary complex structure, lithology and age, physical properties, and state of stress, which are documented in full in the site chapters of this volume, are here synthesized across the expeditions

Metamorphic reworking of a high pressure–low temperature mélange along the Motagua fault, Guatemala: A record of Neocomian and Maastrichtian transpressional tectonics

The Guatemala suture zone is a major east–west left-lateral strike slip boundary that separates the North American and Caribbean plates in Guatemala. The Motagua fault, the central active strand of the suture zone, underwent two major collisional events within a system otherwise dominated by strike–slip motion. The first event is recorded by high-pressure/low temperature (HP/LT) eclogites and related rocks that occur within serpentinites both north and south of the Motagua fault. Lawsonite eclogites south of the fault are not significantly retrograded and give 40Ar/39Ar ages of 125–116 Ma and Sm–Nd mineral isochrons of 144–132 Ma. Eclogites north of the fault give similar Sm–Nd isochron ages (131–126 Ma) but otherwise differ in that they are strongly overprinted by a lower pressure assemblage and, along with associated HP/LT rocks, give much younger 40Ar/39Ar ages of 88–55 Ma indicating a later amphibolite facies metamorphic event. We propose therefore that all serpentinite hosted eclogites along the Motagua fault formed at essentially the same time in different parts of a laterally extensive Lower Cretaceous forearc subduction system, but subsequently underwent different histories. The southern assemblages were thrust southwards (present coordinates) immediately after HP metamorphism whereas the northern association was retrograded during a later collision that thrust it northward at ca. 70 Ma. They were subsequently juxtaposed opposite each other by major strike slip motion. This model implies that the HP rocks on opposing sides of the Motagua fault evolved along a plate boundary that underwent both dip slip and strike slip motion throughout the Late Cretaceous as a result of oblique convergence. The juxtaposition of a convergent and strike slip system means that HP/LT rocks within serpentinites can be found at depth along much of the modern Guatemala suture zone and its eastward extension into the northern Caribbean. Both sets of assemblages were exhumed relatively recently by the uplift of mountain ranges on both sides of the fault caused by movement along a restraining bend. Recent exhumation explains the apparently lack of offset of surface outcrops along a major strike slip fault

Towards Regional Scale Stormwater Flood Management Strategies through Rapid Preliminary Intervention Screening

This is the final version. Available on open access from MDPI via the DOI in this recordData Availability Statement: Data underpinning this study is available upon reasonable request through contacting the authors.his paper presents the advantages and opportunities for rapid preliminary intervention screening to enhance inclusion of green infrastructures in regional scale stormwater management. Stormwater flooding is widely recognised as a significant and worsening natural hazard across the globe; however, current management approaches aimed at the site scale do not adequately explore opportunities for integrated management at the regional scale at which decisions are made. This research addresses this gap through supporting the development of stormwater management strategies, including green infrastructure, at a regional scale. This is achieved through upscaling a modelling approach using a spatially explicit inundation model (CADDIES) coupled with an economic model of inundation loss (OpenProFIA) to support widescale evaluation of green infrastructure during the informative early-stage development of stormwater management strategies. This novel regional scale approach is demonstrated across a case study of the San Francisco Bay Area, spanning 8300 sq km. The main opportunity from this regional approach is to identify spatial and temporal trends which are used to inform regional planning and direct future detailed modelling efforts. The study highlights several limitations of the new method, suggesting it should be applied as part of a suite of landscape management approaches; however, highlights that it has the potential to complement existing stormwater management toolkitsNatural Capital ProjectEngineering and Physical Sciences Research Council (EPSRC)Natural Environment Research Council (NERC)Betty and Gordon Moore FoundationNanyang Technological University and National Research Foundation, Prime Minister’s Office, SingaporeEngineering School, Universidad de Buenos Aire

Effectiveness of Non-nucleoside Reverse-Transcriptase Inhibitor-Based Antiretroviral Therapy in Women Previously Exposed to a Single Intrapartum Dose of Nevirapine: A Multi-country, Prospective Cohort Study

In a comparative cohort study, Jeffrey Stringer and colleagues investigate the risk of ART failure in women who received single-dose nevirapine for PMTCT, and assess the duration of increased risk

Emergence and Persistence of Minor Drug-Resistant HIV-1 Variants in Ugandan Women after Nevirapine Single-Dose Prophylaxis

BACKGROUND: Nevirapine (NVP) single-dose is still a widely used antiretroviral prophylaxis for the prevention of vertical HIV-1 transmission in resource-limited settings. However, the main disadvantage of the Non-nucleoside Reverse Transcriptase Inhibitor (NNRTI) NVP is the rapid selection of NVP-resistant virus with negative implications for subsequent NNRTI-based long-term antiretroviral therapy (ART). Here, we analysed the emergence of drug-resistant HIV-1 including minor variants in the early phase after NVP single-dose prophylaxis and the persistence of drug-resistant virus over time. METHODS AND FINDINGS: NVP-resistant HIV-1 harbouring the K103N and/or Y181C resistance mutations in the HIV-1 reverse transcriptase gene was measured from 1 week up to 18 months after NVP single-dose prophylaxis in 29 Ugandan women using allele-specific PCR assays capable of detecting drug-resistant variants representing less than 1% of the whole viral population. In total, drug-resistant HIV-1 was identified in 18/29 (62%) women; rates increased from 18% to 38% and 44% at week 1, 2, 6, respectively, and decreased to 18%, 25%, 13% and 4% at month 3, 6, 12 and 18, respectively. The proportion of NVP-resistant virus of the total viral population was significantly higher in women infected with subtype D (median 40.5%) as compared to subtype A (median 1.3%; p = 0.032, Mann-Whitney U test). 33% of resistant virus was not detectable at week 2 but was for the first time measurable 6-12 weeks after NVP single-dose prophylaxis. Three (10%) women harboured resistant virus in proportions >10% still at month 6. CONCLUSIONS: Current WHO guidelines recommend an additional postnatal intake of AZT and 3TC for one week to avoid NVP resistance formation. Our findings indicate that a 1-week medication might be too short to impede the emergence of NVP resistance in a substantial proportion of women. Furthermore, subsequent NNRTI-based ART should not be started earlier than 12 months after NVP single-dose prophylaxis

AIDS-defining events and deaths in HIV-infected children and adolescents on antiretrovirals: a 14-year study in Thailand

BACKGROUND: Data are scarce on the long-term clinical outcomes of perinatally HIV-infected children and adolescents receiving antiretroviral therapy (ART) in low/middle-income countries. We assessed the incidence of mortality before (early) and after (late) 6-month of ART and of the composite outcome of new/recurrent AIDS-defining-event or death >6 months after ART start (late AIDS/death) and their associated factors. METHODS: Study population was perinatally HIV-infected children (≤18 years) initiating ART within the Program for HIV Prevention and Treatment observational cohort (NCT00433030). Factors associated with late AIDS/death were assessed using competing risk regression models accounting for loss-to-follow-up, and included baseline and time-updated variables. RESULTS: Among 619 children, "early" mortality incidence was 99 deaths per 1000-PYFU (95%CI; 69-142) and "late" mortality 6 per 1000-PYFU (95%CI; 4-9). Of the 553 children alive >6 months after ART initiation, median age at ART initiation was 6.4 years, CD4% 8.2% and HIV-RNA 5.1 log10 copies/mL. 38 (7%) children developed late AIDS/death after median time of 3.3 years: 24 died and 24 experienced new/recurrent AIDS-defining-events (10 subsequently died). Factors independently associated with late AIDS/death were: current age ≥13 years (adjusted sub-distribution hazard-ratio 4.9; 95%CI; 2.4-10.1), HIV-RNA always ≥400 copies/mL (12.3; 4.0-37.6), BMI-z-score always <-2 SD (13.7; 3.4-55.7), and hemoglobin <8g/dL at least once (4.6; 2.0-10.5). CONCLUSIONS: After the initial 6 months of ART, being an adolescent, persistent viremia, poor nutritional status and severe anemia were associated with poor clinical outcomes. This supports the need for novel interventions that target children, particularly adolescents with poor growth and uncontrolled viremia

The impact of pre-exposure prophylaxis (PrEP) on HIV epidemics in Africa and India: A simulation study

Background: Pre-exposure prophylaxis (PrEP) is a promising new HIV prevention method, especially for women. An urgent demand for implementation of PrEP is expected at the moment efficacy has been demonstrated in clinical trials. We explored the long-term impact of PrEP on HIV transmission in different HIV epidemics. Methodology/Principal Findings: We used a mathematical model that distinguishes the general population, sex workers and their clients. PrEP scenarios varying in effectiveness, coverage and target group were modeled in the epidemiological settings of Botswana, Nyanza Province in Kenya, and Southern India. We also studied the effect of condom addition or condom substitution during PrEP use. Main outcome was number of HIV infections averted over ten years of PrEP use. PrEP strategies with high effectiveness and high coverage can have a substantial impact in African settings. In Southern India, by contrast, the number of averted HIV infections in different PrEP scenarios would be much lower. The impact of PrEP may be strongly diminished or even reversed by behavioral disinhibition, especially in scenarios with low coverage and low effectiveness. However, additional condom use during low coverage and low effective PrEP doubled the amount of averted HIV infections. Conclusions/Significance: The public health impact of PrEP can be substantial. However, this impact may be diminished, or even reversed, by changes in risk behavior. Implementation of PrEP strategies should therefore come on top of current condom campaigns, not as a substitution

Adherence to Combination Prophylaxis for Prevention of Mother-to-Child-Transmission of HIV in Tanzania

BACKGROUND: Since 2008, Tanzanian guidelines for prevention of mother-to-child-transmission of HIV (PMTCT) recommend combination regimen for mother and infant starting in gestational week 28. Combination prophylaxis is assumed to be more effective and less prone to resistance formation compared to single-drug interventions, but the required continuous collection and intake of drugs might pose a challenge on adherence especially in peripheral resource-limited settings. This study aimed at analyzing adherence to combination prophylaxis under field conditions in a rural health facility in Kyela, Tanzania. METHODS AND FINDINGS: A cohort of 122 pregnant women willing to start combination prophylaxis in Kyela District Hospital was enrolled in an observational study. Risk factors for decline of prophylaxis were determined, and adherence levels before, during and after delivery were calculated. In multivariate analysis, identified risk factors for declining pre-delivery prophylaxis included maternal age below 24 years, no income-generating activity, and enrolment before 24.5 gestational weeks, with odds ratios of 5.8 (P = 0.002), 4.4 (P = 0.015) and 7.8 (P = 0.001), respectively. Women who stated to have disclosed their HIV status were significantly more adherent in the pre-delivery period than women who did not (P = 0.004). In the intra- and postpartum period, rather low drug adherence rates during hospitalization indicated unsatisfactory staff performance. Only ten mother-child pairs were at least 80% adherent during all intervention phases; one single mother-child pair met a 95% adherence threshold. CONCLUSIONS: Achieving adherence to combination prophylaxis has shown to be challenging in this rural study setting. Our findings underline the need for additional supervision for PMTCT staff as well as for clients, especially by encouraging them to seek social support through status disclosure. Prophylaxis uptake might be improved by preponing drug intake to an earlier gestational age. Limited structural conditions of a healthcare setting should be taken into serious account when implementing PMTCT combination prophylaxis

Miscellaneous Rheumatic Diseases [73-83]: 73. Is There a Delay in Specialist Referral of Hot Swollen Joint?

Background: Patients with acute, hot, swollen joints commonly present to general practitioners, emergency departments and/or acute admitting teams rather than directly to rheumatology. It is imperative to consider septic arthritis in the differential diagnosis of these patients. The British Society of Rheumatology (BSR) has produced guidelines for the management of this condition, which include recommendations for early specialist referral and joint aspiration of all patients with suspected septic arthritis. We examined whether the initial management of patients with acute hot swollen joint(s) at University College London Hospital (UCLH) follows BSR guidelines. Methods: For the period Feb to Nov 2009, appropriate patients were identified by searching the UCLH database using the diagnostic terms, "pyogenic arthritis”, "septic arthritis” and "gout”; and from all joint aspirate requests sent to microbiology. Medical notes were obtained and any patients who had elective arthroscopies or chronic (> 6 weeks) symptoms were excluded. Data were collected on the time taken from the onset of symptoms to specialist (orthopaedic/rheumatology) referral and joint aspiration, collection of blood cultures and antibiotic treatment with or without microbiology advice. Results: Twenty patients were identified with hot swollen (18 monoarticular, 3 prosthetic) joint(s) of < 2 weeks duration. Of whom, 3/20 (15%) were admitted directly to rheumatology, 7/20 (35%) to the acute admissions unit, 3/20 (15%) to orthopaedic, 4/20 (20%) to a medical team and 1/20 (5%) to general surgery. In 19 (95%) cases, specialist (rheumatology/orthopaedic) advice was sought. Of 14 cases not seen directly by specialists 9 (64%) were referred at 24-48 h and 5 (36%) at 48-192 h. All 20 patients had joint aspiration. In 9/20 (45%) of cases, joint aspiration was performed in less than 6 h, 3/20 (15%) cases at 6-24h and 6/20 (30%) cases at 24-192 h and was not recorded in two patients. Of these, crystals were identified in two and one was culture positive. Blood cultures were received for only 6/20 (30%) of cases and only clearly documented to have been taken prior to antibiotic therapy and none were positive. Of 14/20 (70%) started on antibiotic treatment empirically, only 6 (42%) were preceded by joint aspiration. In the 6 patients not treated with antibiotics due to low index of suspicion of septic arthritis, synovial fluid and blood cultures were negative. Microbiology advice was sought in 10/20 (50%) of cases by the admitting teams but the timing of this advice is unclear. Conclusions: Despite the provision of 24 h rheumatology and orthopaedic cover at UCLH, we found a significant delay in acute medical firms seeking specialist advice on the management of patients with acute, hot swollen joints with subsequent deviation from BSR guidelines. Consequently, we plan to increase awareness of these guidelines amongst medical firms at UCLH. Disclosure statement: All authors have declared no conflicts of interes

Maternal anaemia and duration of zidovudine in antiretroviral regimens for preventing mother-to-child transmission: a randomized trial in three African countries

Background: Although substantiated by little evidence, concerns about zidovudine-related anaemia in pregnancy have influenced antiretroviral (ARV) regimen choice for preventing mother-to-child transmission of HIV-1, especially in settings where anaemia is common. Methods: Eligible HIV-infected pregnant women in Burkina Faso, Kenya and South Africa were followed from 28 weeks of pregnancy until 12–24 months after delivery (n = 1070). Women with a CD4 count of 200-500cells/mm3 and gestational age 28–36 weeks were randomly assigned to zidovudine-containing triple-ARV prophylaxis continued during breastfeeding up to 6-months, or to zidovudine during pregnancy plus single-dose nevirapine (sd-NVP) at labour. Additionally, two cohorts were established, women with CD4 counts: \u3c200 cells/mm3 initiated antiretroviral therapy, and \u3e500 cells/mm3 received zidovudine during pregnancy plus sd-NVP at labour. Mild (haemoglobin 8.0-10.9 g/dl) and severe anaemia (haemoglobin \u3c 8.0 g/dl) occurrence were assessed across study arms, using Kaplan-Meier and multivariable Cox proportional hazards models. Results: At enrolment (corresponded to a median 32 weeks gestation), median haemoglobin was 10.3 g/dl (IQR = 9.2-11.1). Severe anaemia occurred subsequently in 194 (18.1%) women, mostly in those with low baseline haemoglobin, lowest socio-economic category, advanced HIV disease, prolonged breastfeeding (≥6 months) and shorter ARV exposure. Severe an- aemia incidence was similar in the randomized arms (equivalence P-value = 0.32). After 1–2 months of ARV’s, severe anaemia was significantly reduced in all groups, though remained highest in the low CD4 cohort. Conclusions: Severe anaemia occurs at a similar rate in women receiving longer triple zidovudine-containing regimens or shorter prophylaxis. Pregnant women with pre-existing anaemia and advanced HIV disease require close monitoring