When to Start Antiretroviral Therapy

The question of when to start combination antiretroviral therapy for treatment-naïve patients has always been controversial. This is particularly true in the current era, with major guidelines recommending very different treatment strategies. Despite a lack of clarity regarding the optimal time to begin therapy, there has been a recent shift toward earlier initiation. This more aggressive approach is driven by several observations. First, effective viral suppression with therapy can prevent non-AIDS-related morbidity and mortality. Second, therapy can prevent irreversible harm to the human immune system. Third, therapy may prevent transmission of HIV to others, and thus have a potential public health benefit. For patients who are motivated and willing to initiate early treatment, the collective benefits of early therapy may outweigh the well-documented risks of antiretroviral medications

The Evolution of Bat Vestibular Systems in the Face of Potential Antagonistic Selection Pressures for Flight and Echolocation

PMCID: PMC3634842This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Composite likelihood estimation of demographic parameters

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background: Most existing likelihood-based methods for fitting historical demographic models to DNA sequence polymorphism data to do not scale feasibly up to the level of whole-genome data sets. Computational economies can be achieved by incorporating two forms of pseudo-likelihood: composite and approximate likelihood methods. Composite likelihood enables scaling up to large data sets because it takes the product of marginal likelihoods as an estimator of the likelihood of the complete data set. This approach is especially useful when a large number of genomic regions constitutes the data set. Additionally, approximate likelihood methods can reduce the dimensionality of the data by summarizing the information in the original data by either a sufficient statistic, or a set of statistics. Both composite and approximate likelihood methods hold promise for analyzing large data sets or for use in situations where the underlying demographic model is complex and has many parameters. This paper considers a simple demographic model of allopatric divergence between two populations, in which one of the population is hypothesized to have experienced a founder event, or population bottleneck. A large resequencing data set from human populations is summarized by the joint frequency spectrum, which is a matrix of the genomic frequency spectrum of derived base frequencies in two populations. A Bayesia

Verbal autopsy completion rate and factors associated with undetermined cause of death in a rural resource-poor setting of Tanzania

UNLABELLED\ud \ud ABSTRACT:\ud \ud BACKGROUND\ud \ud Verbal autopsy (VA) is a widely used tool to assign probable cause of death in areas with inadequate vital registration systems. Its uses in priority setting and health planning are well documented in sub-Saharan Africa (SSA) and Asia. However, there is a lack of data related to VA processing and completion rates in assigning causes of death in a community. There is also a lack of data on factors associated with undetermined causes of death documented in SSA. There is a need for such information for understanding the gaps in VA processing and better estimating disease burden.\ud \ud OBJECTIVE\ud \ud The study's intent was to determine the completion rate of VA and factors associated with assigning undetermined causes of death in rural Tanzania.\ud \ud METHODS\ud \ud A database of deaths reported from the Ifakara Health and Demographic Surveillance System from 2002 to 2007 was used. Completion rates were determined at the following stages of processing: 1) death identified; 2) VA interviews conducted; 3) VA forms submitted to physicians; 4) coding and assigning of cause of death. Logistic regression was used to determine factors associated with deaths coded as "undetermined."\ud \ud RESULTS\ud \ud The completion rate of VA after identification of death and the VA interview ranged from 83% in 2002 and 89% in 2007. Ninety-four percent of deaths submitted to physicians were assigned a specific cause, with 31% of the causes coded as undetermined. Neonates and child deaths that occurred outside health facilities were associated with a high rate of undetermined classification (33%, odds ratio [OR] = 1.33, 95% confidence interval [CI] (1.05, 1.67), p = 0.016). Respondents reporting high education levels were less likely to be associated with deaths that were classified as undetermined (24%, OR = 0.76, 95% CI (0.60, -0.96), p = 0.023). Being a child of the deceased compared to a partner (husband or wife) was more likely to be associated with undetermined cause of death classification (OR = 1.35, 95% CI (1.04, 1.75), p = 0.023).\ud \ud CONCLUSION\ud \ud Every year, there is a high completion rate of VA in the initial stages of processing; however, a number of VAs are lost during the processing. Most of the losses occur at the final step, physicians' determination of cause of death. The type of respondent and place of death had a significant effect on final determination of the plausible cause of death. The finding provides some insight into the factors affecting full coverage of verbal autopsy diagnosis and the limitations of causes of death based on VA in SSA. Although physician review is the most commonly used method in ascertaining probable cause of death, we suggest further work needs to be done to address the challenges faced by physicians in interpreting VA forms. There is need for an alternative to or improvement of the methods of physician review

Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV

A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7 TeV is presented. The data were collected at the LHC, with the CMS detector, and correspond to an integrated luminosity of 4.6 inverse femtobarns. No significant excess is observed above the background expectation, and upper limits are set on the Higgs boson production cross section. The presence of the standard model Higgs boson with a mass in the 270-440 GeV range is excluded at 95% confidence level.Comment: Submitted to JHE

Do Leaf Cutting Ants Cut Undetected? Testing the Effect of Ant-Induced Plant Defences on Foraging Decisions in Atta colombica

Leaf-cutting ants (LCAs) are polyphagous, yet highly selective herbivores. The factors that govern their selection of food plants, however, remain poorly understood. We hypothesized that the induction of anti-herbivore defences by attacked food plants, which are toxic to either ants or their mutualistic fungus, should significantly affect the ants' foraging behaviour. To test this “induced defence hypothesis,” we used lima bean (Phaseolus lunatus), a plant that emits many volatile organic compounds (VOCs) upon herbivore attack with known anti-fungal or ant-repellent effects. Our results provide three important insights into the foraging ecology of LCAs. First, leaf-cutting by Atta ants can induce plant defences: Lima bean plants that were repeatedly exposed to foraging workers of Atta colombica over a period of three days emitted significantly more VOCs than undamaged control plants. Second, the level to which a plant has induced its anti-herbivore defences can affect the LCAs' foraging behaviour: In dual choice bioassays, foragers discriminated control plants from plants that have been damaged mechanically or by LCAs 24 h ago. In contrast, strong induction levels of plants after treatment with the plant hormone jasmonic acid or three days of LCA feeding strongly repelled LCA foragers relative to undamaged control plants. Third, the LCA-specific mode of damaging leaves allows them to remove larger quantities of leaf material before being recognized by the plant: While leaf loss of approximately 15% due to a chewing herbivore (coccinelid beetle) was sufficient to significantly increase VOC emission levels after 24 h, the removal of even 20% of a plant's leaf area within 20 min by LCAs did not affect its VOC emission rate after 24 h. Taken together, our results support the “induced defence hypothesis” and provide first empirical evidence that the foraging behaviour of LCAs is affected by the induction of plant defence responses

Effect of a mixed reality-based intervention on arm, hand, and finger function on chronic stroke

[EN] Background: Virtual and mixed reality systems have been suggested to promote motor recovery after stroke. Basing on the existing evidence on motor learning, we have developed a portable and low-cost mixed reality tabletop system that transforms a conventional table in a virtual environment for upper limb rehabilitation. The system allows intensive and customized training of a wide range of arm, hand, and finger movements and enables interaction with tangible objects, while providing audiovisual feedback of the participants' performance in gamified tasks. This study evaluates the clinical effectiveness and the acceptance of an experimental intervention with the system in chronic stroke survivors. Methods: Thirty individuals with stroke were included in a reversal (A-B-A) study. Phase A consisted of 30 sessions of conventional physical therapy. Phase B consisted of 30 training sessions with the experimental system. Both interventions involved flexion and extension of the elbow, wrist, and fingers, and grasping of different objects. Sessions were 45-min long and were administered three to five days a week. The body structures (Modified Ashworth Scale), functions (Motricity Index, Fugl-Meyer Assessment Scale), activities (Manual Function Test, Wolf Motor Function Test, Box and Blocks Test, Nine Hole Peg Test), and participation (Motor Activity Log) were assessed before and after each phase. Acceptance of the system was also assessed after phase B (System Usability Scale, Intrinsic Motivation Inventory). Results: Significant improvement was detected after the intervention with the system in the activity, both in arm function measured by the Wolf Motor Function Test (p < 0.01) and finger dexterity measured by the Box and Blocks Test (p < 0.01) and the Nine Hole Peg Test (p < 0.01); and participation (p < 0.01), which was maintained to the end of the study. The experimental system was reported as highly usable, enjoyable, and motivating. Conclusions: Our results support the clinical effectiveness of mixed reality interventions that satisfy the motor learning principles for upper limb rehabilitation in chronic stroke survivors. This characteristic, together with the low cost of the system, its portability, and its acceptance could promote the integration of these systems in the clinical practice as an alternative to more expensive systems, such as robotic instruments.The authors wish to thank the staff and patients of the Servicio de Neurorrehabilitación y Daño Cerebral de los Hospitales NISA for their involvement in the study. The authors also wish to thank the staff of LabHuman for their support in this project, especially Francisco Toledo and José Roda for their assistance. This study was funded in part by the Project TEREHA (IDI-20110844) and Project NeuroVR (TIN2013-44741-R) of the Ministerio de Economia y Competitividad of Spain, the Project Consolider-C (SEJ2006-14301/PSIC) of the Ministerio de Educacion y Ciencia of Spain, the "CIBER of Physiopathology of Obesity and Nutrition, an initiative of ISCIII", and the Excellence Research Program PROMETEO of the Conselleria de Educacion of Generalitat Valenciana (2008-157).Colomer Font, C.; Llorens Rodríguez, R.; Noé Sebastián, E.; Alcañiz Raya, ML. (2016). Effect of a mixed reality-based intervention on arm, hand, and finger function on chronic stroke. Journal of NeuroEngineering and Rehabilitation. 13:1-10. https://doi.org/10.1186/s12984-016-0153-6S11013Fregni F, Pascual-Leone A. Hand motor recovery after stroke: tuning the orchestra to improve hand motor function. Cogn Behav Neurol. 2006;19(1):21–33.Patten C, Condliffe EG, Dairaghi CA, Lum PS. 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J Rehabil Med. 2001;33(3):110–3.Wolf SL, Catlin PA, Ellis M, Archer AL, Morgan B, Piacentino A. Assessing Wolf Motor Function Test as Outcome Measure for Research in Patients After Stroke. Stroke. 2001;32(7):1635–9.Reinkensmeyer DJ, Wolbrecht ET, Chan V, Chou C, Cramer SC, Bobrow JE. Comparison of three-dimensional, assist-as-needed robotic arm/hand movement training provided with Pneu-WREX to conventional tabletop therapy after chronic stroke. Am J Phys Med Rehabil. 2012;91(11 Suppl 3):S232–41.Takahashi CD, Der-Yeghiaian L, Le V, Motiwala RR, Cramer SC. Robot-based hand motor therapy after stroke. Brain. 2008;131(Pt 2):425–37.Sale P, Mazzoleni S, Lombardi V, Galafate D, Massimiani MP, Posteraro F, et al. Recovery of hand function with robot-assisted therapy in acute stroke patients: a randomized-controlled trial. Int J Rehabil Res. 2014;37(3):236–42.Hwang CH, Seong JW, Son DS. 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Comparison of Bone and Renal Effects In HIV-infected Adults Switching to Abacavir or Tenofovir Based Therapy in a Randomized Trial

Our objective was to compare the bone and renal effects among HIV-infected patients randomized to abacavir or tenofovir-based combination anti-retroviral therapy.In an open-label randomized trial, HIV-infected patients were randomized to switch from zidovudine/lamivudine (AZT/3TC) to abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC). We measured bone mass density (BMD) and bone turnover biomarkers (osteocalcin, osteocalcin, procollagen type 1 N-terminal propeptide (P1NP), alkaline phosphatase, type I collagen cross-linked C-telopeptide (CTx), and osteoprotegerin). We assessed renal function by estimated creatinine clearance, plasma cystatin C, and urinary levels of creatinine, albumin, cystatin C, and neutrophil gelatinase-associated lipocalin (NGAL). The changes from baseline in BMD and renal and bone biomarkers were compared across study arms.Of 40 included patients, 35 completed 48 weeks of randomized therapy and follow up. BMD was measured in 33, 26, and 27 patients at baseline, week 24, and week 48, respectively. In TDF/FTC-treated patients we observed significant reductions from baseline in hip and lumbar spine BMD at week 24 (-1.8% and -2.5%) and week 48 (-2.1% and -2.1%), whereas BMD was stable in patients in the ABC/3TC arm. The changes from baseline in BMD were significantly different between study arms. All bone turnover biomarkers except osteoprotegerin increased in the TDF/FTC arm compared with the ABC/3TC arm, but early changes did not predict subsequent loss of BMD. Renal function parameters were similar between study arms although a small increase in NGAL was detected among TDF-treated patients.Switching to TDF/FTC-based therapy led to decreases in BMD and increases in bone turnover markers compared with ABC/3TC-based treatment. No major difference in renal function was observed.Clinicaltrials.gov NCT00647244