Long-term immunologic response to antiretroviral therapy in low-income countries: a collaborative analysis of prospective studies

BACKGROUND: Few data are available on the long-term immunologic response to antiretroviral therapy (ART) in resource-limited settings, where ART is being rapidly scaled up using a public health approach, with a limited repertoire of drugs. OBJECTIVES: To describe immunologic response to ART among ART patients in a network of cohorts from sub-Saharan Africa, Latin America, and Asia. STUDY POPULATION/METHODS: Treatment-naive patients aged 15 and older from 27 treatment programs were eligible. Multilevel, linear mixed models were used to assess associations between predictor variables and CD4 cell count trajectories following ART initiation. RESULTS: Of 29 175 patients initiating ART, 8933 (31%) were excluded due to insufficient follow-up time and early lost to follow-up or death. The remaining 19 967 patients contributed 39 200 person-years on ART and 71 067 CD4 cell count measurements. The median baseline CD4 cell count was 114 cells/microl, with 35% having less than 100 cells/microl. Substantial intersite variation in baseline CD4 cell count was observed (range 61-181 cells/microl). Women had higher median baseline CD4 cell counts than men (121 vs. 104 cells/microl). The median CD4 cell count increased from 114 cells/microl at ART initiation to 230 [interquartile range (IQR) 144-338] at 6 months, 263 (IQR 175-376) at 1 year, 336 (IQR 224-472) at 2 years, 372 (IQR 242-537) at 3 years, 377 (IQR 221-561) at 4 years, and 395 (IQR 240-592) at 5 years. In multivariable models, baseline CD4 cell count was the most important determinant of subsequent CD4 cell count trajectories. CONCLUSION: These data demonstrate robust and sustained CD4 response to ART among patients remaining on therapy. Public health and programmatic interventions leading to earlier HIV diagnosis and initiation of ART could substantially improve patient outcomes in resource-limited settings.

Toxicity and early treatment outcomes in low- and intermediate-risk prostate cancer managed by high-dose-rate brachytherapy as a monotherapy

PURPOSE: To determine the acute and late genitourinary (GU) and gastrointestinal (GI) toxicity and present short-term biochemical no evidence of disease (bNED) rates after high-dose-rate brachytherapy (HDR-B) monotherapy. METHODS AND MATERIALS: Between October 2003 and June 2006, 36 patients with low (28) and intermediate (8) risk prostate cancer (PCA) were treated by HDR-B monotherapy. All patients received one implant and four fractions of 9.5Gy within 48h for a total prescribed dose (PD) of 38Gy. Five patients received hormonal therapy (HT). Median age was 63.5 years and median followup was 3 years (range, 0.4-4 years). Toxicity was scored according to the CTCAE version 3.0. Biochemical failure was defined according to the Phoenix criteria. RESULTS: Acute and late Grade 3 GU toxicity was observed in 1 (3%) and 4 (11%) patients, respectively. Grade 3 GI toxicity was absent. The three- year bNED survival rate was 100%. The sexual preservation rate in patients without HT was 75%. Late Grade 3 GU toxicity was associated with the planning target volume (PTV) V(100) (% PTV receiving > or =100% of the PD; p=0.036), D(90) (dose delivered to 90% of the PTV; p=0.02), and the urethral V(120) (urethral volume receiving > or =120% of the PD; p=0.043). The urethral V(120) was associated with increased PTV V(100) (p<0.001) and D(90) (p=0.003). CONCLUSIONS: After HDR-B monotherapy, late Grade 3 GU toxicity is associated with the urethral V(120) and the V(100) and D(90) of the PTV. Decrease of the irradiated urethral volume may reduce the GU toxicity and potentially improve the therapeutic ratio of this treatment.

Critical issues in managing protected areas by multi-stakeholder participation - analysis of a process in the Swiss Alps

Balancing the frequently conflicting priorities of conservation and economic development poses a challenge to management of the Swiss Alps Jungfrau-Aletsch World Heritage Site (WHS). This is a complex societal problem that calls for a knowledge-based solution. This in turn requires a transdisciplinary research framework in which problems are defined and solved cooperatively by actors from the scientific community and the life-world. In this article we re-examine studies carried out in the region of the Swiss Alps Jungfrau-Aletsch WHS, covering three key issues prevalent in transdisciplinary settings: integration of stakeholders into participatory processes; perceptions and positions; and negotiability and implementation. In the case of the Swiss Alps Jungfrau-Aletsch WHS the transdisciplinary setting created a situation of mutual learning among stakeholders from different levels and backgrounds. However, the studies showed that the benefits of such processes of mutual learning are continuously at risk of being diminished by the power play inherent in participatory approaches.

Is ITS-2 rDNA suitable marker for genetic characterization of Sarcoptes mites from different wild animals in different geographic areas?

The present study examined the relationship among individual Sarcoptes scabiei mites from 13 wild mammalian populations belonging to nine species in four European countries using the second internal transcribed spacer (ITS-2) of nuclear ribosomal DNA (rDNA) as genetic marker. The ITS-2 plus primer flanking 5.8S and 28S rDNA (ITS-2+) was amplified from individual mites by polymerase chain reaction (PCR) and the amplicons were sequenced directly. A total of 148 ITS-2+ sequences of 404bp in length were obtained and 67 variable sites were identified (16.59%). UPGMA analyses did not show any geographical or host-specific clustering, and a similar outcome was obtained using population pairwise Fst statistics. These results demonstrated that ITS-2 rDNA does not appear to be suitable for examining genetic diversity among mite populations.

Engaging Local Communities in Low Emissions Land-Use Planning: a Case Study from Laos

Reducing Emissions from Deforestation and Forest Degradation and enhancing forest carbon stocks (REDD+) is a performance-based payment mechanism currently being debated in international and national environmental policy and planning forums. As the mechanism is based on conditionality, payments must reflect land stewards’ level of compliance with carbon-efficient management practices. However, lack of clarity in land governance and carbon rights could undermine REDD+ implementation. Strategies are needed to avoid perverse incentives resulting from the commoditization of forest carbon stocks and, importantly, to identify and secure the rights of legitimate recipients of future REDD+ payments. We propose a landscape-level approach to address potential conflicts related to carbon tenure and REDD+ benefit sharing. We explore various land-tenure scenarios and their implications for carbon ownership in the context of a research site in northern Laos. Our case study shows that a combination of relevant scientific tools, knowledge, and participatory approaches can help avoid the marginalization of rural communities during the REDD+ process. The findings demonstrate that participatory land-use planning is an important step in ensuring that local communities are engaged in negotiating REDD+ schemes and that such negotiations are transparent. Local participation and agreements on land-use plans could provide a sound basis for developing efficient measurement, reporting, and verification systems for REDD+.

Immunodeficiency at the start of combination antiretroviral therapy in low-, middle-, and high-income countries

OBJECTIVE To describe the CD4 cell count at the start of combination antiretroviral therapy (cART) in low-income (LIC), lower middle-income (LMIC), upper middle-income (UMIC), and high-income (HIC) countries. METHODS Patients aged 16 years or older starting cART in a clinic participating in a multicohort collaboration spanning 6 continents (International epidemiological Databases to Evaluate AIDS and ART Cohort Collaboration) were eligible. Multilevel linear regression models were adjusted for age, gender, and calendar year; missing CD4 counts were imputed. RESULTS In total, 379,865 patients from 9 LIC, 4 LMIC, 4 UMIC, and 6 HIC were included. In LIC, the median CD4 cell count at cART initiation increased by 83% from 80 to 145 cells/μL between 2002 and 2009. Corresponding increases in LMIC, UMIC, and HIC were from 87 to 155 cells/μL (76% increase), 88 to 135 cells/μL (53%), and 209 to 274 cells/μL (31%). In 2009, compared with LIC, median counts were 13 cells/μL [95% confidence interval (CI): -56 to +30] lower in LMIC, 22 cells/μL (-62 to +18) lower in UMIC, and 112 cells/μL (+75 to +149) higher in HIC. They were 23 cells/μL (95% CI: +18 to +28 cells/μL) higher in women than men. Median counts were 88 cells/μL (95% CI: +35 to +141 cells/μL) higher in countries with an estimated national cART coverage >80%, compared with countries with <40% coverage. CONCLUSIONS Median CD4 cell counts at the start of cART increased 2000-2009 but remained below 200 cells/μL in LIC and MIC and below 300 cells/μL in HIC. Earlier start of cART will require substantial efforts and resources globally.

Matrix pore water in low-permeable crystalline bedrock: An archive for the palaeohydrogeological evolution of the Olkiluoto Investigation Site

Matrix pore water in the connected inter- and intragranular pore space of low-permeable crystalline bedrock interacts with flowing fracture groundwater predominately by diffusion. Based on the slow exchange between the two water reservoirs, matrix pore water acts as an archive of past changes in fracture groundwater compositions and thus of the palaeohydrological history of a site. Matrix pore water of crystalline bedrock from the Olkiluoto investigation site (SW Finland) was characterised using the stable water isotopes (δ18O, δ2H), combined with the concentrations of dissolved chloride and bromide as natural tracers. The comparison of tracer concentrations in pore water and present-day fracture groundwater suggest for the pore water the presence of old, dilute meteoric water components that infiltrated into the fractures during various warm climate stages. These different meteoric components can be discerned based on the diffusion distance between the two reservoirs and be brought into context with the palaeohydrological evolution of the site.

Impact of a 4th generation iterative reconstruction technique on image quality in low-dose computed tomography of the chest in immunocompromised patients

PURPOSE To determine the image quality of an iterative reconstruction (IR) technique in low-dose MDCT (LDCT) of the chest of immunocompromised patients in an intraindividual comparison to filtered back projection (FBP) and to evaluate the dose reduction capability. MATERIALS AND METHODS 30 chest LDCT scans were performed in immunocompromised patients (Brilliance iCT; 20-40 mAs; mean CTDIvol: 1.7 mGy). The raw data were reconstructed using FBP and the IR technique (iDose4™, Philips, Best, The Netherlands) set to seven iteration levels. 30 routine-dose MDCT (RDCT) reconstructed with FBP served as controls (mean exposure: 116 mAs; mean CDTIvol: 7.6 mGy). Three blinded radiologists scored subjective image quality and lesion conspicuity. Quantitative parameters including CT attenuation and objective image noise (OIN) were determined. RESULTS In LDCT high iDose4™ levels lead to a significant decrease in OIN (FBP vs. iDose7: subscapular muscle 139.4 vs. 40.6 HU). The high iDose4™ levels provided significant improvements in image quality and artifact and noise reduction compared to LDCT FBP images. The conspicuity of subtle lesions was limited in LDCT FBP images. It significantly improved with high iDose4™ levels (> iDose4). LDCT with iDose4™ level 6 was determined to be of equivalent image quality as RDCT with FBP. CONCLUSION iDose4™ substantially improves image quality and lesion conspicuity and reduces noise in low-dose chest CT. Compared to RDCT, high iDose4™ levels provide equivalent image quality in LDCT, hence suggesting a potential dose reduction of almost 80%.

Immunodeficiency in children starting antiretroviral therapy in low-, middle-, and high-income countries.

BACKGROUND The CD4 cell count or percent (CD4%) at the start of combination antiretroviral therapy (cART) is an important prognostic factor in children starting therapy and an important indicator of program performance. We describe trends and determinants of CD4 measures at cART initiation in children from low-, middle-, and high-income countries. METHODS We included children aged <16 years from clinics participating in a collaborative study spanning sub-Saharan Africa, Asia, Latin America, and the United States. Missing CD4 values at cART start were estimated through multiple imputation. Severe immunodeficiency was defined according to World Health Organization criteria. Analyses used generalized additive mixed models adjusted for age, country, and calendar year. RESULTS A total of 34,706 children from 9 low-income, 6 lower middle-income, 4 upper middle-income countries, and 1 high-income country (United States) were included; 20,624 children (59%) had severe immunodeficiency. In low-income countries, the estimated prevalence of children starting cART with severe immunodeficiency declined from 76% in 2004 to 63% in 2010. Corresponding figures for lower middle-income countries were from 77% to 66% and for upper middle-income countries from 75% to 58%. In the United States, the percentage decreased from 42% to 19% during the period 1996 to 2006. In low- and middle-income countries, infants and children aged 12-15 years had the highest prevalence of severe immunodeficiency at cART initiation. CONCLUSIONS Despite progress in most low- and middle-income countries, many children continue to start cART with severe immunodeficiency. Early diagnosis and treatment of HIV-infected children to prevent morbidity and mortality associated with immunodeficiency must remain a global public health priority.

How much management is enough? Stakeholder views on forest management in fire-prone areas in central Portugal

With the increasing pressure to improve the contribution of forests to help dealing with global changes, it is critical to understand the different perceptions of those involved in the forest. How do forest owners, managers and members of local communities who often depend on the forest, value it and what are the problems affecting the forests in terms of being able to meet these new challenges? In Portugal, this task has taken on an even greater priority as more than 90% of the forest is private and forest management relies on the individual decisions of thousands of forest owners. To understand stakeholder views on forest and forest management, a transversal social perception survey was implemented in the form of a case study of central Portugal which included decision-makers, local technicians, forest owners and the general public. The results show that there is a consensus on the main issues affecting forests and forest management. A shift from classic forest owners to the emergence of indifferent forest owners was observed, although this shift has not been recognized by the forest owners in the survey, who maintain the individual management of their properties.

Desertification and Global Change: Innovative Management of Scarce Resources in Semi-Arid Areas. Experiences from development and research: Challenges for a better future

While most events related to the International Year of Deserts and Desertification 2006 took mainly a problem-oriented perspective and approach, the Bern Symposium held in May 2006 tried to adopt a more positive attitude by attempting to take stock of experience as well as best and worst practices in the past, both in development practice and in research. Through this deliberate focus on potentials, positive experiences, solutions and pathways, predominant passive and reactive attitudes and hopelessness might be better overcome. The Symposium was organized by CDE, NCCR North-South and Forum SLM.

P-T-t estimation of syn-kinematic strain in low-grade quartz-feldspar bearing rocks using thermodynamic modeling and 40Ar/39Ar dating techniques: example of the Plan-de-Phasy shear zone unit (Briançonnais Zone, Western Alps)

Pressure–Temperature–time (P–T–t) estimates of the syn-kinematic strain at the peak-pressure conditions reached during shallow underthrusting of the Briançonnais Zone in the Alpine subduction zone was made by thermodynamic modelling and 40Ar/39Ar dating in the Plan-de-Phasy unit (SE of the Pelvoux Massif, Western Alps). The dated phengite minerals crystallized syn-kinematically in a shear zone indicating top-to-the-N motion. By combining X-ray mapping with multi-equilibrium calculations, we estimate the phengite crystallization conditions at 270 ± 50 °C and 8.1 ± 2 kbar at an age of 45.9 ± 1.1 Ma. Combining this P–T–t estimate with data from the literature allows us to constrain the timing and geometry of Alpine continental subduction. We propose that the Briançonnais units were scalped on top of the slab during ongoing continental subduction and exhumed continuously until collision.