Optimizing ribavirin dose in HIV/hepatitis C (HCV) co-infected individuals treated for HCV

Hepatitis C (HCV) and HIV share common transmission pathways and the acquisition of both viruses are relatively common. Concurrent treatment for HCV with highly active anti-retroviral therapy (HAART) should be considered in HIV co-infected individuals to decrease the progression of liver damage. Adverse effects and less satisfactory treatment outcomes are often concerns when treating co-infected individuals. Although, direct acting antivirals (DAAs) may increase SVR, they may not be possible because of drug-drug interactions. he objective of this study is to investigate the difference in response rates of HCV treatment in HIV co-infected inmates with varying doses of ribavirin. Retrospective medical chart reviews of 52 HCV/HIV co-infected inmates who underwent HCV therapy between 2003 and 2010. All received standard doses of pegylated interferon alpha 2a or 2b and 800–1600 mg of ribavirin depending on weight. The recommended dosage for genotypes 2 and 3 is 800 mg/day. For other genotypes, if weight is<75 kg, the recommended ribavirin dose is 1000 mg/day or 1200 mg/day if>75 kg. Efficacy was defined as attaining sustained virological response (SVR) six months post treatment. Univariate analyses was performed using SPSS-18; Chi-square test with p-value<0.05 was defined significant. 52 co-infected (3 females & 49 males) were identified. Mean age was 40±7 years. Caucasians accounted for 84.6%; First Nations for 13.5% and Asians 1.9%. 36 were concurrently on HAART. The genotype distribution was: geno 1, 66.0%; geno 2, 7.5%; geno 3, 26.4%. SVR by ribavirin dosage ratio (actual dosage/recommended dosage):=1.0; 41.2% (14/34),>1.0; 58.8% (20/34). Doses greater than 1.5 times were associated with higher adverse events and lower SVR. Suboptimal doses of weight-based ribavirin may be contributing to a lower treatment response in HCV/HIV co-infectants. In our experience, the optimal dose of ribavirin is between 1 and 1.2 times the current recommended dose. We recommend that ribavirin dose be individualized in co-infected in order to enhance the likelihood of achieving SVR. Dual therapy is more practical in many of our population because of chaotic lifestyle. Therefore optimizing the ribavirin dose should be initially undertaken

Mechanical Control of Spin States in Spin-1 Molecules and the Underscreened Kondo Effect

The ability to make electrical contact to single molecules creates opportunities to examine fundamental processes governing electron flow on the smallest possible length scales. We report experiments in which we controllably stretch individual cobalt complexes having spin S = 1, while simultaneously measuring current flow through the molecule. The molecule's spin states and magnetic anisotropy were manipulated in the absence of a magnetic field by modification of the molecular symmetry. This control enabled quantitative studies of the underscreened Kondo effect, in which conduction electrons only partially compensate the molecular spin. Our findings demonstrate a mechanism of spin control in single-molecule devices and establish that they can serve as model systems for making precision tests of correlated-electron theories.Comment: main text: 5 pages, 4 figures; supporting information attached; to appear in Science

CPU, GPU i FPGA implementacija MALD algoritma za otkrivanje nepravilnosti na površini keramičkih pločica

This paper addresses adjustments, implementation and performance comparison of the Moving Average with Local Difference (MALD) method for ceramic tile surface defects detection. Ceramic tile production process is completely autonomous, except the final stage where human eye is required for defects detection. Recent computational platform development and advances in machine vision provides us with several options for MALD algorithm implementation. In order to exploit the shortest execution time for ceramic tile production process, the MALD method is implemented on three different platforms: CPU, GPU and FPGA, and it is implemented on each platform in at least two ways. Implementations are done in MATLAB’s MEX/C++, C++, CUDA/C++, VHDL and Assembly programming languages. Execution times are measured and compared for different algorithms and their implementations on different computational platforms.U ovom radu razmatra se prilagodba, implementacija i usporedba performansi metode pomičnog usrednjavanja s lokalnom diferencijom (MALD) s primjenom u otkrivanju površinskih nedostataka na keramičkim pločicama. Proizvodna linija keramičkih pločica je autonomna sve do zadnje faze u kojoj je potreban ljudski vid kako bi se otkrili eventualni nedostaci na keramičkim pločicama. Nedavnim razvojem računalnih platformi i razvojem metoda računalnog vida omogućena je implementacija MALD metode na nekoliko načina. U nastojanju skraćenja vremena potrebnog za proizvodnju keramičkih pločica, MALD metoda je implementirana u trima različitim platformama: CPU (central processing unit), GPU (graphic processing unit) i FPGA (field programmable gate array), te s barem dva različita algoritma. Implementacija je izvršena sa MATLAB MEX/C++, C++, CUDA/C++, VHDL te Asembler programskim jezicima. Izmjerena vremena obrade su me.usobno uspore.ena za različite algoritme i njihove implementacije na različitim računalnim platformama

The Selective Personalized Radio-Immunotherapy for Locally Advanced NSCLC Trial (SPRINT)

Purpose/Objective(s): Standard therapy for unresectable locally advanced non-small cell lung cancer (LA-NSCLC) is concurrent chemoradiotherapy (chemoRT), which is usually followed by adjuvant durvalumab. We performed a prospective trial testing sequential pembrolizumab and risk-adapted radiotherapy without chemotherapy for biomarker-selected LA-NSCLC patients. Materials/Methods: Patients with AJCC version 8 stage III NSCLC or unresectable stage II NSCLC and ECOG performance status 0-1 were eligible for this trial. Subjects with PD-L1 tumor proportion score (TPS) ≥ 50% received three cycles of induction pembrolizumab (200 mg, every 21 days), underwent restaging FDG-PET/CT, received risk-adapted thoracic radiotherapy (55 Gy delivered to tumors or lymph nodes with metabolic tumor volume exceeding 20 cc and 48 Gy delivered to smaller lesions, all in 20 daily fractions), and then received up to 13 cycles of additional pembrolizumab. Subjects with PD-L1 TPS \u3c 50% received concurrent chemoRT, and adjuvant durvalumab was recommended for patients without disease progression. The primary study endpoint was one-year progression-free survival (PFS) for subjects treated with pembrolizumab and radiotherapy (pembroRT), which we hypothesized would exceed 65%. Other study endpoints included 1-year overall survival (OS) and rates of clinician-scored (CTCAE v. 4.03) and patient-reported (PRO-CTCAE) adverse events observed over one year. Results: Twenty-five subjects with PD-L1 TPS ≥ 50% and 12 subjects with PD-L1 TPS \u3c 50% from three institutions were enrolled between August 2018 and November 2021. Median age was 70. Twenty-four subjects had stage II-IIIA disease, and 13 had stage IIIB-IIIC disease. Except for PD-L1 TPS, subject characteristics did not differ significantly across treatment groups. Ten out of the 12 subjects with ChemoRT received adjuvant durvalumab, and one received adjuvant osimertinib for EGFR mutation. The median follow-up duration is 15 months. Compared to patients treated with chemoRT, treatment with pembroRT has yielded numerically higher 1-year PFS (72% v. 46%, log rank p=0.232) and OS (91% v. 73%, log rank p=0.213) rates. Similar rates of grade 3 physician-scored adverse events have been observed with pembroRT (24%) and chemoRT (25%). Less severe patient-reported adverse events occurred with pembroRT compared to chemoRT (See Table). Conclusion: Treatment with pembrolizumab and risk-adapted radiotherapy without chemotherapy is a promising approach for LA-NSCLC patients with PD-L1 TPS ≥ 50%. In addition to yielding high disease control rates, this strategy appears to reduce patient-reported adverse events compared to standard chemoRT and adjuvant therapy

Talking Less during Social Interactions Predicts Enjoyment: A Mobile Sensing Pilot Study

Can we predict which conversations are enjoyable without hearing the words that are spoken? A total of 36 participants used a mobile app, My Social Ties, which collected data about 473 conversations that the participants engaged in as they went about their daily lives. We tested whether conversational properties (conversation length, rate of turn taking, proportion of speaking time) and acoustical properties (volume, pitch) could predict enjoyment of a conversation. Surprisingly, people enjoyed their conversations more when they spoke a smaller proportion of the time. This pilot study demonstrates how conversational properties of social interactions can predict psychologically meaningful outcomes, such as how much a person enjoys the conversation. It also illustrates how mobile phones can provide a window into everyday social experiences and well-being

A cartilage tissue engineering approach combining starch-polycaprolactone fibre mesh scaffolds with bovine articular chondrocytes

In the present work we originally tested the suitability of corn starch-polycaprolactone (SPCL) scaffolds for pursuing a cartilage tissue engineering approach. Bovine articular chondrocytes were seeded on SPCL scaffolds under dynamic conditions using spinner flasks (total of 4 scaffolds per spinner flask using cell suspensions of 0.5×106 cells/ml) and cultured under orbital agitation for a total of 6 weeks. Poly(glycolic acid) (PGA) non-woven scaffolds and bovine native articular cartilage were used as standard controls for the conducted experiments. PGA is a kind of standard in tissue engineering approaches and it was used as a control in that sense. The tissue engineered constructs were characterized at different time periods by scanning electron microscopy (SEM), hematoxylin-eosin (H&E) and toluidine blue stainings, immunolocalisation of collagen types I and II, and dimethylmethylene blue (DMB) assay for glycosaminoglycans (GAG) quantification assay. SEM results for SPCL constructs showed that the chondrocytes presented normal morphological features, with extensive cells presence at the surface of the support structures, and penetrating the scaffolds pores. These observations were further corroborated by H&E staining. Toluidine blue and immunohistochemistry exhibited extracellular matrix deposition throughout the 3D structure. Glycosaminoglycans, and collagen types I and II were detected. However, stronger staining for collagen type II was observed when compared to collagen type I. The PGA constructs presented similar features toSPCLat the end of the 6 weeks. PGA constructs exhibited higher amounts of matrix glycosaminoglycans when compared to the SPCL scaffolds. However, we also observed a lack of tissue in the central area of the PGA scaffolds. Reasons for these occurrences may include inefficient cells penetration, necrosis due to high cell densities, or necrosis related with acidic by-products degradation. Such situation was not detected in the SPCL scaffolds, indicating the much better biocompatibility of the starch based scaffolds

Evidence for directional selection at a novel major histocompatibility class I marker in wild common frogs (Rana temporaria) exposed to a viral pathogen (Ranavirus).

(c) 2009 Teacher et al. This 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.Whilst the Major Histocompatibility Complex (MHC) is well characterized in the anuran Xenopus, this region has not previously been studied in another popular model species, the common frog (Rana temporaria). Nor, to date, have there been any studies of MHC in wild amphibian host-pathogen systems. We characterise an MHC class I locus in the common frog, and present primers to amplify both the whole region, and specifically the antigen binding region. As no more than two expressed haplotypes were found in over 400 clones from 66 individuals, it is likely that there is a single class I locus in this species. This finding is consistent with the single class I locus in Xenopus, but contrasts with the multiple loci identified in axolotls, providing evidence that the diversification of MHC class I into multiple loci likely occurred after the Caudata/Anura divergence (approximately 350 million years ago) but before the Ranidae/Pipidae divergence (approximately 230 mya). We use this locus to compare wild populations of common frogs that have been infected with a viral pathogen (Ranavirus) with those that have no history of infection. We demonstrate that certain MHC supertypes are associated with infection status (even after accounting for shared ancestry), and that the diseased populations have more similar supertype frequencies (lower F(ST)) than the uninfected. These patterns were not seen in a suite of putatively neutral microsatellite loci. We interpret this pattern at the MHC locus to indicate that the disease has imposed selection for particular haplotypes, and hence that common frogs may be adapting to the presence of Ranavirus, which currently kills tens of thousands of amphibians in the UK each year

BPIFB1 is a lung-specific autoantigen associated with interstitial lung disease.

Interstitial lung disease (ILD) is a complex and heterogeneous disorder that is often associated with autoimmune syndromes. Despite the connection between ILD and autoimmunity, it remains unclear whether ILD can develop from an autoimmune response that specifically targets the lung parenchyma. We examined a severe form of autoimmune disease, autoimmune polyglandular syndrome type 1 (APS1), and established a strong link between an autoimmune response to the lung-specific protein BPIFB1 (bactericidal/permeability-increasing fold-containing B1) and clinical ILD. Screening of a large cohort of APS1 patients revealed autoantibodies to BPIFB1 in 9.6% of APS1 subjects overall and in 100% of APS1 subjects with ILD. Further investigation of ILD outside the APS1 disorder revealed BPIFB1 autoantibodies present in 14.6% of patients with connective tissue disease-associated ILD and in 12.0% of patients with idiopathic ILD. The animal model for APS1, Aire⁻/⁻ mice, harbors autoantibodies to a similar lung antigen (BPIFB9); these autoantibodies are a marker for ILD. We found that a defect in thymic tolerance was responsible for the production of BPIFB9 autoantibodies and the development of ILD. We also found that immunoreactivity targeting BPIFB1 independent of a defect in Aire also led to ILD, consistent with our discovery of BPIFB1 autoantibodies in non-APS1 patients. Overall, our results demonstrate that autoimmunity targeting the lung-specific antigen BPIFB1 may contribute to the pathogenesis of ILD in patients with APS1 and in subsets of patients with non-APS1 ILD, demonstrating the role of lung-specific autoimmunity in the genesis of ILD

The assessment and rehabilitation of prospective memory problems in people with neurological disorders: A review

People with neurological disorders often report difficulty with prospective memory (PM), that is, remembering to do things they had intended to do. This paper briefly reviews the literature regarding the neuropsychology of PM function, concluding that from the clinical perspective, PM is best considered in terms of its separable but interacting mnemonic and executive components. Next, the strengths and limitations in the current clinical assessment of PM, including the assessment of component processes, desktop analogues of PM tasks, and naturalistic PM tasks, are outlined. The evidence base for the rehabilitation of PM is then considered, focusing on retraining PM, using retrospective memory strategies, problem-solving training, and finally, electronic memory aids. It is proposed that further research should focus on establishing the predictive validity of PM assessment, and refining promising rehabilitation techniques