The Slab Puzzle of the Alpine‐Mediterranean Region: Insights from a new, High‐Resolution, Shear‐Wave Velocity Model of the Upper Mantle

Mediterranean tectonics since the Lower Cretaceous has been characterized by a multi‐phase subduction and collision history with temporally and spatially‐variable, small‐scale plate configurations. A new shear‐wave velocity model of the Mediterranean upper mantle (MeRE2020), constrained by a very large set of over 200,000 broadband (8‐350 s), inter‐station, Rayleigh‐wave, phase‐velocity curves, illuminates the complex structure and fragmentation of the subducting slabs. Phase‐velocity maps computed using these measurements were inverted for depth‐dependent, shear‐wave velocities using a stochastic particle‐swarm‐optimization algorithm (PSO). The resulting three‐dimensional (3‐D) model makes possible an inventory of slab segments across the Mediterranean. Fourteen slab segments of 200‐800 km length along‐strike are identified. We distinguish three categories of subducted slabs: attached slabs reaching down to the bottom of the model; shallow slabs of shorter length in down‐dip direction, terminating shallower than 300 km depth; and detached slab segments. The location of slab segments are consistent with and validated by the intermediate‐depth seismicity, where it is present. The new high‐resolution tomography demonstrates the intricate relationships between slab fragmentation and the evolution of the relatively small and highly curved subduction zones and collisional orogens characteristic of the Mediterranean realm

Long- term remission status in pediatric obsessive-compulsive disorder : Evaluating the predictive value of symptom severity after treatment

Funding Information: This work was supported by the Tryg Foundation [grant number 122892] and the Department of Child and Adolescent Psychiatry, Aarhus University Hospital, Psychiatry. Publisher Copyright: © 2022 The Author(s)It is unknown if long-term remission for pediatric obsessive-compulsive disorder (OCD) patients is associated with post-treatment OCD symptom severity. The aim of the present study was to evaluate if post-treatment symptom severity cut-offs can discriminate remitters from non-remitters in pediatric OCD patients during three years of follow-up. All participants (N = 269) from the Nordic Long-term OCD Treatment Study (NordLOTS) undergoing stepped-care treatment were included. Patients were rated with the Clinical Global Impression – Severity Scale (CGI-S) one (n = 186), two (n = 167), and three years (n = 166) after first-line cognitive-behavioral therapy. Post-treatment symptom severity scores as well as percentage reductions during treatment evaluated with the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) were analyzed using receiver operating characteristics according to the CGI-S remission scores (< 2) at follow-up. Post-treatment CY-BOCS severity scores acceptably discriminated remitters from non-remitters at one-year follow-up, but poorly for the two- and three-year follow-up. Severity percentage reduction during treatment did not discriminate remission status acceptably at any follow-up point. Post-treatment OCD symptom severity status seems to have little discriminative value for long-term remission status in pediatric patients. Further research is warranted to detect post-treatment factors of prognostic value.Peer reviewe

Adherence to first-line antiretroviral therapy affects non-virologic outcomes among patients on treatment for more than 12 months in Lusaka, Zambia

Background High-level adherence to antiretroviral therapy (ART) is associated with favourable patient outcomes. In resource-constrained settings, however, there are few validated measures. We examined the correlation between clinical outcomes and the medication possession ratio (MPR), a pharmacy-based measure of adherence

Estimating the Capacity for ART Provision in Tanzania with the Use of Data on Staff Productivity and Patient Losses

BACKGROUND: International targets for access to antiretroviral therapy (ART) have over-estimated the capacity of health systems in low-income countries in Sub-Saharan Africa. The WHO target for number on treatment by end 2005 for Tanzania was 10 times higher than actually achieved. The target of the national Care and Treatment Plan (CTP) was also not reached. We aimed at estimating the capacity for ART provision and created five scenarios for ART production given existing resource limitations. METHODS: A situation analysis including scrutiny of staff factors, such as available data on staff and patient factors including access to ART and patient losses, made us conclude that the lack of clinical staff is the main limiting factor for ART scale-up, assuming that sufficient drugs and supplies are provided by donors. We created a simple formula to estimate the number of patients on ART based on availability and productivity of clinical staff, time needed to initiate vs maintain a patient on ART and patient losses using five different scenarios with varying levels of these parameters. FINDINGS: Our scenario assuming medium productivity (40% higher than that observed in 2002) and medium loss of patients (20% in addition to 15% first-year mortality) coincides with the actual reported number of patients initiated on ART up to 2008, but is considerably below the national CTP target of 90% coverage for 2009, corresponding to 420,000 on ART and 710,000 life-years saved (LY's). Our analysis suggests that a coverage of 40% or 175,000 on treatment and 350,000 LY's saved is more achievable. CONCLUSION: A comparison of our scenario estimations and actual output 2006-2008 indicates that a simple user-friendly dynamic model can estimate the capacity for ART scale-up in resource-poor settings based on identification of a limiting staff factor and information on availability of this staff and patient losses. Thus, it is possible to set more achievable targets

The level of CD147 expression correlates with cyclophilin-induced signalling and chemotaxis

<p>Abstract</p> <p>Background</p> <p>Previous studies identified CD147 as the chemotactic receptor on inflammatory leukocytes for extracellular cyclophilins (eCyp). However, CD147 is not known to associate with signal transducing molecules, so other transmembrane proteins, such as proteoglycans, integrins, and CD98, were suggested as receptor or co-receptor for eCyp. CD147 is ubiquitously expressed on many cell types, but relationship between the level of CD147 expression and cellular responses to eCyp has never been analyzed. Given the role of eCyp in pathogenesis of many diseases, it is important to know whether cellular responses to eCyp are regulated at the level of CD147 expression.</p> <p>Results</p> <p>Here, we manipulated CD147 expression levels on HeLa cells using RNAi and investigated the signalling and chemotactic responses to eCypA. Both Erk activation and chemotaxis correlated with the level of CD147 expression, with cells exhibiting low level expression being practically unresponsive to eCypA.</p> <p>Conclusions</p> <p>Our results provide the first demonstration of a chemotactic response of HeLa cells to eCypA, establish a correlation between the level of CD147 expression and the magnitude of cellular responses to eCypA, and indicate that CD147 may be a limiting factor in the receptor complex determining cyclophilin-induced Erk activation and cell migration.</p

Barriers to the care of HIV-infected children in rural Zambia: a cross-sectional analysis

<p>Abstract</p> <p>Background</p> <p>Successful antiretroviral treatment programs in rural sub-Saharan Africa may face different challenges than programs in urban areas. The objective of this study was to identify patient characteristics, barriers to care, and treatment responses of HIV-infected children seeking care in rural Zambia.</p> <p>Methods</p> <p>Cross-sectional analysis of HIV-infected children seeking care at Macha Hospital in rural southern Zambia. Information was collected from caretakers and medical records.</p> <p>Results</p> <p>192 HIV-infected children were enrolled from September 2007 through September 2008, 28% of whom were receiving antiretroviral therapy (ART) at enrollment. The median age was 3.3 years for children not receiving ART (IQR 1.8, 6.7) and 4.5 years for children receiving ART (IQR 2.7, 8.6). 91% travelled more than one hour to the clinic and 26% travelled more than 5 hours. Most participants (73%) reported difficulties accessing the clinic, including insufficient money (60%), lack of transportation (54%) and roads in poor condition (32%). The 54 children who were receiving ART at study enrollment had been on ART a median of 8.6 months (IQR: 2.7, 19.5). The median percentage of CD4⁺T cells was 12.4 (IQR: 9.2, 18.6) at the start of ART, and increased to 28.6 (IQR: 23.5, 36.1) at the initial study visit. However, the proportion of children who were underweight decreased only slightly, from 70% at initiation of ART to 61% at the initial study visit.</p> <p>Conclusion</p> <p>HIV-infected children in rural southern Zambia have long travel times to access care and may have poorer weight gain on ART than children in urban areas. Despite these barriers, these children had a substantial rise in CD4⁺T cell counts in the first year of ART although longer follow-up may indicate these gains are not sustained.</p

A systematic review of task- shifting for HIV treatment and care in Africa

BACKGROUND: Shortages of human resources for health (HRH) have severely hampered the rollout of antiretroviral therapy (ART) in sub-Saharan Africa. Current rollout models are hospital- and physician-intensive. Task shifting, or delegating tasks performed by physicians to staff with lower-level qualifications, is considered a means of expanding rollout in resource-poor or HRH-limited settings. METHODS: We conducted a systematic literature review. Medline, the Cochrane library, the Social Science Citation Index, and the South African National Health Research Database were searched with the following terms: task shift*, balance of care, non-physician clinicians, substitute health care worker, community care givers, primary healthcare teams, cadres, and nurs* HIV. We mined bibliographies and corresponded with authors for further results. Grey literature was searched online, and conference proceedings searched for abstracts. RESULTS: We found 2960 articles, of which 84 were included in the core review. 51 reported outcomes, including research from 10 countries in sub-Saharan Africa. The most common intervention studied was the delegation of tasks (especially initiating and monitoring HAART) from doctors to nurses and other non-physician clinicians. Five studies showed increased access to HAART through expanded clinical capacity; two concluded task shifting is cost effective; 9 showed staff equal or better quality of care; studies on non-physician clinician agreement with physician decisions was mixed, with the majority showing good agreement. CONCLUSIONS: Task shifting is an effective strategy for addressing shortages of HRH in HIV treatment and care. Task shifting offers high-quality, cost-effective care to more patients than a physician-centered model. The main challenges to implementation include adequate and sustainable training, support and pay for staff in new roles, the integration of new members into healthcare teams, and the compliance of regulatory bodies. Task shifting should be considered for careful implementation where HRH shortages threaten rollout programmes

Patient-centred tuberculosis treatment delivery under programmatic conditions in Tanzania: a cohort study

<p>Abstract</p> <p>Background</p> <p>Directly observed therapy (DOT) remains the cornerstone of the global tuberculosis (TB) control strategy. Tanzania, one of the 22 high-burden countries regarding TB, changed the first-line treatment regimen to contain rifampicin-containing fixed-dose combination for the full 6 months of treatment. As daily health facility-based DOT for this long period is not feasible for the patient, nor for the health system, Tanzania introduced patient centred treatment (PCT). PCT allows patients to choose for daily DOT at a health facility or at their home by a supporter of choice. The introduction of fixed dose combinations in the intensive and continuation phase made PCT feasible by eliminating the risk of selective drug taking by patients and reducing the number of tablets to be taken. The approach was tested in three districts with the objective to assess the effect of this strategy on TB treatment outcomes</p> <p>Methods</p> <p>Cohort analysis comparing patients treated under the PCT strategy (registered April-September 2006) with patients treated under health-facility-based DOT (registered April-September 2005). The primary outcome was the cure rate. Differences were assessed by calculating the risk ratios. Associations between characteristics of the supporters and treatment outcomes in the group of patients opting for home-based DOT were assessed through logistic regression.</p> <p>Results</p> <p>In the PCT cohort there were 1208 patients and 1417 were included in the historic cohort. There was no significant difference in cure rates between the cohorts (risk ratio [RR]: 1.06; 95% confidence interval [CI]: 0.96-1.16). In the PCT cohort, significantly more patients had successful treatment (cure or treatment completed; RR: 1.10; 95%CI: 1.01-1.15). There were no characteristics of supporters that were associated with treatment outcome.</p> <p>Conclusion</p> <p>The PCT approach showed similar cure rates and better treatment success rates compared to daily health-facility DOT. The results indicate that there are no specific prerequisites for the supporter chosen by the patient. The programmatic setting of the study lends strong support for scaling-up of TB treatment observation outside the health facility.</p

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

Monitoring Virologic Responses to Antiretroviral Therapy in HIV-Infected Adults in Kenya: Evaluation of a Low-Cost Viral Load Assay

A key advantage of monitoring HIV viral load (VL) in persons receiving antiretroviral therapy (ART) is the ability to detect virologic failure before clinical deterioration or resistance occurs. Detection of virologic failure will help clarify the need for enhanced adherence counseling or a change to second- line therapy. Low-cost, locally performable alternates to expensive VL assays are needed where resources are limited.We monitored the response to 48-week ART in 100 treatment-naïve Kenyan adults using a low-cost VL measurement, the Cavidi reverse transcriptase (RT) assay and gold-standard assays, Roche RNA PCR and Bayer Versant HIV-1 RNA (bDNA) assays. In Altman-Bland plots, the mean difference in viral loads between the three assays was small (<0.5 log(10) copies/mL). However, the limits of agreement between the methods exceeded the biologically relevant change of 0.5 log copies/ml. Therefore, the RT assay cannot be used interchangeably with the other assays to monitor individual patients. The RT assay was 100% sensitive in detecting viral loads of > or =400 copies/ml compared to gold-standard assays. After 24 weeks of treatment, viral load measured by the RT assay was undetectable in 95% of 65 patients with undetectable RNA PCR VL (<400 copies/ml), 90% of 67 patients with undetectable bDNA VL, and 96% of 57 patients with undetectable VL in both RNA PCR and bDNA assays. The negative predictive value of the RT assay was 100% compared to either assay; the positive predictive value was 86% compared to RNA PCR and 70% compared to bDNA.The RT assay compared well with gold standard assays. Our study highlights the importance of not interchanging viral load assays when monitoring an individual patient. Furthermore, the RT assay may be limited by low positive predictive values when used in populations with low prevalence of virologic failure