Evaluation of Viral Load Thresholds for Predicting New World Health Organization Stage 3 and 4 Events in HIV-Infected Children Receiving Highly Active Antiretroviral Therapy

Background: This study evaluated a wide range of viral load (VL) thresholds to identify a cut-point that best predicts new clinical events in children on stable highly active antiretroviral therapy (HAART). Methods: Cox proportional hazards modeling was used to assess the adjusted risk for World Health Organization stage 3 or 4 clinical events (WHO events) as a function of time-varying CD4, VL, and hemoglobin values in a cohort study of Latin American children on HAART >= 6 months. Models were fit using different VL cut-points between 400 and 50,000 copies per milliliter, with model fit evaluated on the basis of the minimum Akaike information criterion value, a standard model fit statistic. Results: Models were based on 67 subjects with WHO events out of 550 subjects on study. The VL cut-points of >2600 and >32,000 copies per milliliter corresponded to the lowest Akaike information criterion values and were associated with the highest hazard ratios (2.0, P = 0.015; and 2.1, P = 0.0058, respectively) for WHO events. Conclusions: In HIV-infected Latin American children on stable HAART, 2 distinct VL thresholds (>2600 and >32,000 copies/mL) were identified for predicting children at significantly increased risk for HIV-related clinical illness, after accounting for CD4 level, hemoglobin level, and other significant factors.

A Two-Stage Aerobic/Anaerobic Denitrifying Horizontal Bioreactor Designed for Treating Ammonium and H2S Simultaneously

A two-stage bioreactor was operated for a period of 140 days in order to develop a post-treatment process based on anaerobic bioxidation of sulfite. This process was designed for simultaneously treating the effluent and biogas of a full-scale UASB reactor, containing significant concentrations of NH4 and H2S, respectively. The system comprised of two horizontal-flow bed-packed reactors operated with different oxygen concentrations. Ammonium present in the effluent was transformed into nitrates in the first aerobic stage. The second anaerobic stage combined the treatment of nitrates in the liquor with the hydrogen sulfide present in the UASB-reactor biogas. Nitrates were consumed with a significant production of sulfate, resulting in a nitrate removal rate of 0.43 kg N m(3) day(-1) and a parts per thousand yen92 % efficiency. Such a removal rate is comparable to those achieved by heterotrophic denitrifying systems. Polymeric forms of sulfur were not detected (elementary sulfur); sulfate was the main product of the sulfide-based denitrifying process. S-sulfate was produced at a rate of about 0.35 kg m(3) day(-1). Sulfur inputs as S-H2S were estimated at about 0.75 kg m(3) day(-1) and Chemical Oxygen Demand (COD) removal rates did not vary significantly during the process. DGGE profiling and 16S rRNA identified Halothiobacillus-like species as the key microorganism supporting this process; such a strain has not yet been previously associated with such bioengineered systems.

Hydrogen and Methane Production, Energy Recovery, and Organic Matter Removal from Effluents in a Two-Stage Fermentative Process

This study evaluates the potential for using different effluents for simultaneous H-2 and CH4 production in a two-stage batch fermentation process with mixed microflora. An appreciable amount of H-2 was produced from parboiled rice wastewater (23.9 mL g(-1) chemical oxygen demand [COD]) and vinasse (20.8 mL g(-1) COD), while other effluents supported CH4 generation. The amount of CH4 produced was minimum for sewage (46.3 mL g(-1) COD), followed by parboiled rice wastewater (115.5 mL g(-1) COD) and glycerol (180.1 mL g(-1) COD). The maximum amount of CH4 was observed for vinasse (255.4 mL g(-1) COD). The total energy recovery from vinasse (10.4 kJ g(-1) COD) corresponded to the maximum COD reduction (74.7 %), followed by glycerol (70.38 %, 7.20 kJ g(-1) COD), parboiled rice wastewater (63.91 %, 4.92 kJ g(-1) COD), and sewage (51.11 %, 1.85 kJ g(-1) COD). The relatively high performance of vinasse in such comparisons could be attributed to the elevated concentrations of macronutrients contained in raw vinasse. The observations are based on kinetic parameters of H-2 and CH4 production and global energy recovery of the process. These observations collectively suggest that organic-rich effluents can be deployed for energy recovery with sequential generation of H-2 and CH4.

A clinical experience of the supraclavicular flap used to reconstruct head and neck defects in late-stage cancer patients

The supraclavicular island flap has been widely used in head and neck reconstruction, providing an alternative to the traditional techniques like regional or free flaps, mainly because of its thin skin island tissue and reliable vascularity. Head and neck patients who require large reconstructions usually present poor clinical and healing conditions. An early experience using this flap for late-stage head and neck tumour treatment is reported. Forty-seven supraclavicular artery flaps were used to treat head and neck oncologic defects after cutaneous, intraoral and pharyngeal tumour resections. Dissection time, complications, donor and reconstructed area outcomes were assessed. The mean time for harvesting the flaps was 50 min by the senior author. All donor sites were closed primarily. Three cases of laryngopharyngectomy reconstruction developed a small controlled (salivary) leak that was resolved with conservative measures. Small or no strictures were detected on radiologic swallowing examinations and all patients regained normal swallowing function. Five patients developed donor site dehiscence. These wounds were treated with regular dressing until healing was complete. There were four distal flap necroses in this series. These necroses were debrided and closed primarily. The supraclavicular flap is pliable for head and neck oncologic reconstruction in late-stage patients. High-risk patients and modified radical neck dissection are not contraindications for its use. The absence of the need to isolate the pedicle offers quick and reliable harvesting. The arc of rotation on the base of the neck provides adequate length for pharyngeal, oral lining and to reconstruct the middle and superior third of the face. (C) 2012 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

CD44(+)/CD24(-) cells and lymph node metastasis in stage I and II invasive ductal carcinoma of the breast

The presence of tumor-initiating cells (CD44(+)/CD24(-)) in solid tumors has been reported as a possible cause of cancer metastasis and treatment failure. Nevertheless, little is know about the presence of CD44(+)/CD24(-) cells within the primary tumor and metastasis. The proportion of CD44(+)/CD24(-) cells was analyzed in 40 samples and in 10 lymph node metastases using flow cytometry phenotyping. Anti-human CD326 (EpCam; FITC), antihuman CD227 (MUC-1; FITC), anti-human CD44 (APC), and anti-human CD24 (PE), anti-ABCG2 (PE), and anti-CXCR4 (PeCy7) were used for phenotype analysis. The mean patient age was 60.5 years (range, 33-87 years); mean primary tumor size (pT) was 1.8 cm (0.5-3.5 cm). The Wilcoxon or Kruskal-Wallis test was used for univariate analyses. Logistic regression was used for multivariate analysis. The median percentage of CD44(+)/CD24(-) cells within primary invasive ductal carcinomas (IDC) was 2.7% (range, 0.2-71.2). In lymph node metastases, we observed a mean of 6.1% (range, 0.07-53.7). The percentage of CD44(+)/CD24(-) cells in IDCs was not associated with age, pT, tumor grade and HER2. We observed a significantly enrichment of CD44(+)/CD24(-) and ABCG2(+) cells in ESA(+) cell population in patients with positive lymph nodes (P = 0.02 and P = 0.04, respectively). Our data suggest that metastatic dissemination is associated with an increase in tumorinitiating cells in stage I and II breast cancer.

Effect of 12 weeks of resistance exercise on post-exercise hypotension in stage 1 hypertensive individuals

Post-exercise hypotension (PEH), the reduction of blood pressure (BP) after a single bout of exercise, is of great clinical relevance. As the magnitude of this phenomenon seems to be dependent on pre-exercise BP values and chronic exercise training in hypertensive individuals leads to BP reduction; PEH could be attenuated in this context. Therefore, the aim of the present study was to investigate whether PEH remains constant after resistance exercise training. Fifteen hypertensive individuals (46 +/- 8 years; 88 +/- 16 kg; 30 +/- 6% body fat; 150 +/- 13/93 +/- 5mm Hg systolic/diastolic BP, SBP/DBP) were withdrawn from medication and performed 12 weeks of moderate-intensity resistance training. Parameters of cardiovascular function were evaluated before and after the training period. Before the training program, hypertensive volunteers showed significant PEH. After an acute moderate-intensity resistance exercise session with three sets of 12 repetitions (60% of one repetition maximum) and a total of seven exercises, BP was reduced post-exercise (45-60 min) by an average of aproximately -22mm Hg for SBP, -8mm Hg for DBP and -13 mm Hg for mean arterial pressure (P<0.05). However, this acute hypotensive effect did not occur after the 12 weeks of training (P>0.05). In conclusion, our data demonstrate that PEH, following an acute exercise session, can indeed be attenuated after 12 weeks of training in hypertensive stage 1 patients not using antihypertensive medication. Journal of Human Hypertension (2012) 26, 533-539; doi:10.1038/jhh.2011.67; published online 7 July 2011

Genetic vaccine for tuberculosis (pVAXhsp65) primes neonate mice for a strong immune response at the adult stage

Abstract Background Vaccination of neonates is generally difficult due to the immaturity of the immune system and consequent higher susceptibility to tolerance induction. Genetic immunization has been described as an alternative to trigger a stronger immune response in neonates, including significant Th1 polarization. In this investigation we analysed the potential use of a genetic vaccine containing the heat shock protein (hsp65) from Mycobacterium leprae (pVAXhsp65) against tuberculosis (TB) in neonate mice. Aspects as antigen production, genomic integration and immunogenicity were evaluated. Methods Hsp65 message and genomic integration were evaluated by RT-PCR and Southern blot, respectively. Immunogenicity of pVAXhsp65 alone or combined with BCG was analysed by specific induction of antibodies and cytokines, both quantified by ELISA. Results This DNA vaccine was transcribed by muscular cells of neonate mice without integration into the cellular genome. Even though this vaccine was not strongly immunogenic when entirely administered (three doses) during early animal's life, it was not tolerogenic. In addition, pVAXhsp65 and BCG were equally able to prime newborn mice for a strong and mixed immune response (Th1 + Th2) to pVAXhsp65 boosters administered later, at the adult life. Conclusion These results suggest that pVAXhsp65 can be safely used as a priming stimulus in neonate animals in prime-boost similar strategies to control TB. However, priming with BCG or pVAXhsp65, directed the ensuing immune response triggered by an heterologous or homologous booster, to a mixed Th1/Th2 pattern of response. Measures as introduction of IL-12 or GM-CSF genes in the vaccine construct or even IL-4 neutralization, are probably required to increase the priming towards Th1 polarization to ensure control of tuberculosis infection.

A comparison between diuretics and angiotensin-receptor blocker agents in patients with stage I hypertension (PREVER-treatment trial): study protocol for a randomized double-blind controlled trial

Abstract Background Cardiovascular disease is the leading cause of death in Brazil, and hypertension is its major risk factor. The benefit of its drug treatment to prevent major cardiovascular events was consistently demonstrated. Angiotensin-receptor blockers (ARB) have been the preferential drugs in the management of hypertension worldwide, despite the absence of any consistent evidence of advantage over older agents, and the concern that they may be associated with lower renal protection and risk for cancer. Diuretics are as efficacious as other agents, are well tolerated, have longer duration of action and low cost, but have been scarcely compared with ARBs. A study comparing diuretic and ARB is therefore warranted. Methods/design This is a randomized, double-blind, clinical trial, comparing the association of chlorthalidone and amiloride with losartan as first drug option in patients aged 30 to 70 years, with stage I hypertension. The primary outcomes will be variation of blood pressure by time, adverse events and development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG. The secondary outcomes will be fatal or non-fatal cardiovascular events: myocardial infarction, stroke, heart failure, evidence of new subclinical atherosclerosis and sudden death. The study will last 18 months. The sample size will be of 1200 participants for group in order to confer enough power to test for all primary outcomes. The project was approved by the Ethics committee of each participating institution. Discussion The putative pleiotropic effects of ARB agents, particularly renal protection, have been disputed, and they have been scarcely compared with diuretics in large clinical trials, despite that they have been at least as efficacious as newer agents in managing hypertension. Even if the null hypothesis is not rejected, the information will be useful for health care policy to treat hypertension in Brazil. Clinical trials registration number ClinicalTrials.gov: NCT00971165

Ornithodoros peropteryx (Acari: Argasidae) in Bolivia: an argasid tick with a single nymphal stage

By the end of the 1960s, the argasid tick Ornithodoros peropteryx was described from larval specimens collected from the bat Peropteryx macrotis in Colombia. Since its original description, no additional record of O. peropteryx has been reported, and its post-larval stages have remained unknown. During July 2010, 18 larvae were collected from 9 bats (Centronycteris maximiliani), resulting in a mean infestation of 2.0 ± 2.2 ticks per bat (range 1–8). These bats were captured in a farm in northeastern Bolivia close to Guaporé River in the border with Brazil. Morphological examinations of the larvae revealed them to represent the species O. peropteryx. One engorged larva that was kept alive in the laboratory moulted to a nymph after 9 days. Fourteen days after the larval moulting, the nymph moulted to an adult female without taking any blood meal during the nymphal period. This adult female was used for a morphological description of the female stage of O. peropteryx. In addition, the larvae were used for a morphological redescription of this stage. One larva and two legs extirpated from the adult female were submitted to DNA extraction and PCR targeting a fragment of the mitochondrial 16S rDNA gene, which yielded DNA sequences at least 11 % divergent from any available argasid sequence in Genbank. We show that O. peropteryx ontogeny is characterized by a single, non-feeding, nymphal stage. This condition has never been reported for ticks.

IFN-γ-induced priming maintains long-term strain-transcending immunity against blood-stage Plasmodium chabaudi malaria

The mechanism by which protective immunity to Plasmodium is lost in the absence of continued exposure to this parasite has yet to be fully elucidated. It has been recently shown that IFN-γ produced during human and murine acute malaria primes the immune response to TLR agonists. In this study, we investigated whether IFN-γ-induced priming is important to maintain long-term protective immunity against Plasmodium chabaudi AS malaria. On day 60 postinfection, C57BL/6 mice still had chronic parasitemia and efficiently controlled homologous and heterologous (AJ strain) challenge. The spleens of chronic mice showed augmented numbers of effector/effector memory (TEM) CD4(+) cells, which is associated with increased levels of IFN-γ-induced priming (i.e., high expression of IFN-inducible genes and TLR hyperresponsiveness). After parasite elimination, IFN-γ-induced priming was no longer detected and protective immunity to heterologous challenge was mostly lost with >70% mortality. Spontaneously cured mice had high serum levels of parasite-specific IgG, but effector T/TEM cell numbers, parasite-driven CD4(+) T cell proliferation, and IFN-γ production were similar to noninfected controls. Remarkably, the priming of cured mice with low doses of IFN-γ rescued TLR hyperresponsiveness and the capacity to control heterologous challenge, increasing the TEM cell population and restoring the CD4(+) T cell responses to parasites. Contribution of TLR signaling to the CD4(+) T cell responses in chronic mice was supported by data obtained in mice lacking the MyD88 adaptor. These results indicate that IFN-γ-induced priming is required to maintain protective immunity against P. chabaudi and aid in establishing the molecular basis of strain-transcending immunity in human malaria.

Ornithodoros peropteryx (Acari Argasidae) in Bolivia an argasid tick with a single nymphal stage

By the end of the 1960s, the argasid tick Ornithodoros peropteryx was described from larval specimens collected from the bat Peropteryx macrotis in Colombia. Since its original description, no additional record of O. peropteryx has been reported, and its post-larval stages have remained unknown. During July 2010, 18 larvae were collected from 9 bats (Centronycteris maximiliani), resulting in a mean infestation of 2.0 ± 2.2 ticks per bat (range 1–8). These bats were captured in a farm in northeastern Bolivia close to Guapore´ River in the border with Brazil. Morphological examinations of the larvae revealed them to represent the species O. peropteryx. One engorged larva that was kept alive in the laboratory moulted to a nymph after 9 days. Fourteen days after the larval moulting, the nymph moulted to an adult female without taking any blood meal during the nymphal period. This adult female was used for a morphological description of the female stage of O. peropteryx. In addition, the larvae were used for a morphological redescription of this stage. One larva and two legs extirpated from the adult female were submitted to DNA extraction and PCR targeting a fragment of the mitochondrial 16S rDNA gene, which yielded DNA sequences at least 11 % divergent from any available argasid sequence in Genbank. We show that O. peropteryx ontogeny is characterized by a single, non-feeding, nymphal stage. This condition has never been reported for ticks.

A two-stage economic succession at the inception of farming in central Portugal. Preliminary examination of possible causes and consequences

[EN]Notwithstanding their scarcity and uneven distribution, zooarchaeological and stable isotope data sets on the Early and Middle Neolithic (5500–3200 cal BC) in the region of Estremadura in Central Portugal strongly suggest that two succeeding stages in subsistence strategies took place: sheep and goat itinerant pastoralism (across large areas) and/or renewed focus on wild food sources (cervid hunting, harvesting marine and freshwater food) which replaced livestock farming within smaller areas and less specialised hunting practices. This economic shift seems to have coincided with two other dramatic changes: the 5.9 kyr cal BP climate event and the onset of megalithism. Possible correlations between these past cultural and palaeoenvironmental phenomena are herein preliminarily outlined. [ES] A pesar de su escasez y distribución desigual, el conjunto de datos arqueozoológicos y de isótopos estables para el Neolítico Antiguo y Medio de la región de Estremadura en el centro de Portugal (5500-3200 a. C. cal), sugiere con claridad dos etapas sucesivas en las estrategias de subsistencia: pastoreo itinerante de ovejas y cabras (ocupando grandes territorios) y/o un renovado interés por los recursos alimenticios silvestres (caza de cérvidos, recolección de alimentos marinos y de agua dulce), que reemplazó otras formas de ganadería más confinadas en el espacio acciones con regímenes de mantenimiento reducidos y unas prácticas de caza menos especializadas. Este cambio económico parece haber ocurrido junto con otros dos cambios dramáticos, el evento climático 5.9 k BP (cal.) y el inicio del megalitismo. Aquí se esbozan de forma preliminar las posibles correlaciones entre estos fenómenos culturales y paleoambientales del pasado.

The reconstruction of paleoclimate variability in Northern Germany, during marine isotope stage 5

In order to obtain a better understanding about the influence of post-depositional diagenesis on speleothem 230Th/U-ages and paleoclimate variability during Marine Isotope Stage (MIS) 5 in northern Germany, four stalagmites from the Riesenberghöhle (RBH) were investigated by thin section analysis, 230Th/U-dating as well as stable oxygen and carbon isotope and laser ablation inductively coupled mass spectrometry (LA-ICPMS) trace element analysis. The RBH is located in the Weser Hills and is one of the northernmost limestone caves in Germany.rnMulti collector (MC) ICPMS 230Th/U-ages and thin section analysis of the RBH stalagmites shows that some growth phases of the stalagmites were diagenetically altered after their deposition. The impact of post-depositional diagenesis (PDD) on the 230Th/U-ages is modeled, and potential processes leading to PDD are discussed. In this context, it is suggested that PDD may be induced by rapid climate change at the inception of the GIS.rnDespite of the dating uncertainties resulting from PDD, 230Th/U-dating shows that the RBH stalagmites grew during the Eemian and most of the Greenland Interstadials (GIS) during MIS 5. Thus, the growth phases of the RBH stalagmites might be related to a reorganization of the Atlantic Meridional Overturning Circulation (AMOC). The stable isotope (δ13C and δ18O) and the trace element variability of the stalagmites reflects rapid changes of past temperature and precipitation on millennial and sub-millennial timescales. These past climate changes can be amplified by orbitally forced variations of the July solar insolation at 65°N.

Methodologies for Synthesizable Programmable Devices based on Multi-Stage Switching Networks

Nowadays the rise of non-recurring engineering (NRE) costs associated with complexity is becoming a major factor in SoC design, limiting both scaling opportunities and the flexibility advantages offered by the integration of complex computational units. The introduction of embedded programmable elements can represent an appealing solution, able both to guarantee the desired flexibility and upgradabilty and to widen the SoC market. In particular embedded FPGA (eFPGA) cores can provide bit-level optimization for those applications which benefits from synthesis, paying on the other side in terms of performance penalties and area overhead with respect to standard cell ASIC implementations. In this scenario this thesis proposes a design methodology for a synthesizable programmable device designed to be embedded in a SoC. A soft-core embedded FPGA (eFPGA) is hence presented and analyzed in terms of the opportunities given by a fully synthesizable approach, following an implementation flow based on Standard-Cell methodology. A key point of the proposed eFPGA template is that it adopts a Multi-Stage Switching Network (MSSN) as the foundation of the programmable interconnects, since it can be efficiently synthesized and optimized through a standard cell based implementation flow, ensuring at the same time an intrinsic congestion-free network topology. The evaluation of the flexibility potentialities of the eFPGA has been performed using different technology libraries (STMicroelectronics CMOS 65nm and BCD9s 0.11μm) through a design space exploration in terms of area-speed-leakage tradeoffs, enabled by the full synthesizability of the template. Since the most relevant disadvantage of the adopted soft approach, compared to a hardcore, is represented by a performance overhead increase, the eFPGA analysis has been made targeting small area budgets. The generation of the configuration bitstream has been obtained thanks to the implementation of a custom CAD flow environment, and has allowed functional verification and performance evaluation through an application-aware analysis.