Treatment for inclusion body myositis

Background Inclusion body myositis (IBM) is a late-onset inflammatory muscle disease (myopathy) associated with progressive proximal and distal limb muscle atrophy and weakness. Treatment options have attempted to target inflammatory and atrophic features of this condition (for example with immunosuppressive and immunomodulating drugs, anabolic steroids, and antioxidant treatments), although as yet there is no known effective treatment for reversing or minimising the progression of inclusion body myositis. In this review we have considered the benefits, adverse effects, and costs of treatment in targeting cardinal effects of the condition, namely muscle atrophy, weakness, and functional impairment. Objectives To assess the effects of treatment for IBM. Search methods On 7 October 2014 we search ed the Cochrane Neuromuscular Disease Group Specialized Register, the Cochrane Central Register for Controlled Trials (CENTRAL), MEDLINE, and EMBASE. Additionally in November 2014 we searched clinical trials registries for ongoing or completed but unpublished trials. Selection criteria We considered randomised or quasi-randomised trials, including cross-over trials, of treatment for IBM in adults compared to placebo or any other treatment for inclusion in the review. We specifically excluded people with familial IBM and hereditary inclusion body myopathy, but we included people who had connective tissue and autoimmune diseases associated with IBM, which may or may not be identified in trials. We did not include studies of exercise therapy or dysphagia management, which are topics of other Cochrane systematic reviews. Data collection and analysis We used standard Cochrane methodological procedures. Main results The review included 10 trials (249 participants) using different treatment regimens. Seven of the 10 trials assessed single agents, and 3 assessed combined agents. Many of the studies did not present adequate data for the reporting of the primary outcome of the review, which was the percentage change in muscle strength score at six months. Pooled data from two trials of interferon beta-1a (n = 58) identified no important difference in normalised manual muscle strength sum scores from baseline to six months (mean difference (MD) -0.06, 95% CI -0.15 to 0.03) between IFN beta-1a and placebo (moderate-quality evidence). A single trial of methotrexate (MTX) (n = 44) provided moderate-quality evidence that MTX did not arrest or slow disease progression, based on reported percentage change in manual muscle strength sum scores at 12 months. None of the fully published trials were adequately powered to detect a treatment effect. We assessed six of the nine fully published trials as providing very low-quality evidence in relation to the primary outcome measure. Three trials (n = 78) compared intravenous immunoglobulin (combined in one trial with prednisone) to a placebo, but we were unable to perform meta-analysis because of variations in study analysis and presentation of trial data, with no access to the primary data for re-analysis. Other comparisons were also reported in single trials. An open trial of anti-T lymphocyte immunoglobulin (ATG) combined with MTX versus MTX provided very low-quality evidence in favour of the combined therapy, based on percentage change in quantitative muscle strength sum scores at 12 months (MD 12.50%, 95% CI 2.43 to 22.57). Data from trials of oxandrolone versus placebo, azathioprine (AZA) combined with MTX versus MTX, and arimoclomol versus placebo did not allow us to report either normalised or percentage change in muscle strength sum scores. A complete analysis of the effects of arimoclomol is pending data publication. Studies of simvastatin and bimagrumab (BYM338) are ongoing. All analysed trials reported adverse events. Only 1 of the 10 trials interpreted these for statistical significance. None of the trials included prespecified criteria for significant adverse events. Authors\u27 conclusions Trials of interferon beta-1a and MTX provided moderate-quality evidence of having no effect on the progression of IBM. Overall trial design limitations including risk of bias, low numbers of participants, and short duration make it difficult to say whether or not any of the drug treatments included in this review were effective. An open trial of ATG combined with MTX versus MTX provided very low-quality evidence in favour of the combined therapy based on the percentage change data given. We were unable to draw conclusions from trials of IVIg, oxandrolone, and AZA plus MTX versus MTX. We need more randomised controlled trials that are larger, of longer duration, and that use fully validated, standardised, and responsive outcome measures

Mapping Strategic Goals and Operational Performance Metrics for Smart Manufacturing Systems

AbstractThe complexity of the relationship of strategic goals to operational performance across the many levels of a manufacturing system inhibits the realization of Smart Manufacturing Systems (SMS). This paper proposes a method for identifying what aspects of a manufacturing system should be addressed to respond to changing strategic goals. The method uses standard techniques in specifying a manufacturing system and the relationship between strategic goals and operational performance metrics. Two existing reference models related to manufacturing operations are represented formally and integrated to support the proposed method. The method is illustrated for a single scenario using agility as a strategic goal. By replicating the proposed method for other strategic goals and with multiple scenarios, a comprehensive set of performance challenges can be identified

Mapping Strategic Goals and Operational Performance Metrics for Smart Manufacturing Systems

The complexity of the relationship of strategic goals to operational performance across the many levels of a manufacturing system inhibits the realization of Smart Manufacturing Systems (SMS). This paper proposes a method for identifying what aspects of a manufacturing system should be addressed to respond to changing strategic goals. The method uses standard techniques in specifying a manufacturing system and the relationship between strategic goals and operational performance metrics. Two existing reference models related to manufacturing operations are represented formally and integrated to support the proposed method. The method is illustrated for a single scenario using agility as a strategic goal. By replicating the proposed method for other strategic goals and with multiple scenarios, a comprehensive set of performance challenges can be identified. (C) 2015 The Authors. Published by Elsevier B.V.111215Ysciescopu

120-GHz HEMT Oscillator With Surface-Wave-Assisted Antenna

Two monolithic microwave integrated circuits (MMICs) have been designed and built to function together as a source of electromagnetic radiation at a frequency of 120 GHz. One of the MMICs is an oscillator and is the highest-power 120-GHz oscillator reported thus far in the literature. The other MMIC is an end-fire antenna that radiates the oscillator signal. Although these MMICs were constructed as separate units and electrically connected with wire bonds, future oscillator/ antenna combinations could readily be fabricated as monolithic integrated units. Such units could be used as relatively high-power solid-state microwave sources in diverse applications that include automotive radar, imaging, scientific instrumentation, communications, and radio astronomy. As such, these units would be attractive alternatives to vacuum-tube oscillators, which are still used to obtain acceptably high power in the frequency range of interest. The oscillator (see figure) includes a high-electron-mobility transistor (HEMT), with gate-periphery dimensions of 4 by 37 m, in a common-source configuration. The series feedback element of the oscillator is a grounded coplanar waveguide (CPW) at the source. The HEMT is biased for class-A operation (meaning that current is conducted throughout the oscillation cycle) to maximize the output power of the oscillator. Input and output impedance-matching circuit elements are designed to maximize output power and to establish the conditions needed for oscillation. The design of the antenna takes advantage of surface waves, which, heretofore, have been regarded as highly disadvantageous because they can leak power and degrade the performances of antennas that have not been designed to exploit them. Measures taken to suppress surface waves have included complex machining of circuit substrates and addition of separate substrates. These measures are difficult to implement in standard MMIC fabrication processes. In contrast, because the design of the present antenna eliminates the need to suppress surface waves, the fabrication of the antenna is fully compatible with standard MMIC fabrication processes

Are patterns of fine-scale spatial genetic structure consistent between sites within tropical tree species?

JRS was funded by the Swiss National Science Foundation (SNF) (http://www.snf.ch/en/Pages/default.aspx) grant number PDFMP3_132479 / 1 awarded to JG. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

PEMBERDAYAAN MASYARAKAT AKAN KEBUTUHAN AIR BERSIH DI DUSUN TEGALSARI DESA KUPANG, KECAMATAN JABON, KABUPATEN SIDOARJO

Pemanasan global saat ini menimbulkan berbagai masalah lingkungan, salah satunya adalah krisis air bersih. Di Indonesia, daerah pesisir merupakan daerah yang sering kekurangan air bersih. Salah satu kawasan pesisir yang kekurangan air bersih adalah Dusun Tegalsari, Desa Kupang, Kecamatan Jabon, Kabupaten Sidoarjo. Salah satu solusi untuk mengatasi masalah tersebut adalah kegiatan amal yang diselenggarakan oleh mahasiswa Universitas Kristen Petra melalui metode service-learning. Pembelajaran service-learning instalasi balam dilakukan untuk memenuhi kebutuhan masyarakat pesisir di lokasi penelitian yang membutuhkan air bersih. Selain itu, siswa belajar untuk berpikir kritis ketika memecahkan masalah sosial dan mempromosikan kepedulian terhadap lingkungan dan masyarakat. Teknologi balam membersihkan air payau dengan material lokal sehingga air menjadi lebih jernih dan dapat digunakan untuk kebutuhan sehari-hari. Cara kerja ini dibagi menjadi tiga langkah/fase. Fase pertama adalah fase pra-implementasi, area disurvei dan beberapa peralatan dibeli dan dipasang. Fase implementasi, perangkat balam dipasang di lokasi. Fase pasca-implementasi, wawancara dengan warga dan penyebaran kuesioner tentang kepuasan terhadap kegiatan service-learning tersebut. Hasilnya adalah lima rumah warga Dusun Tegalsari memiliki fasilitas air sehat yang memadai dan layak digunakan. Kemudian, sebanyak 85% responden yang memasang perangkat BALAM di rumahnya merasa sangat puas dan 15% responden merasa cukup puas

Forensic DNA profiling of tropical timber species in Peninsular Malaysia.

Illegal logging poses a significant threat to the sustainability of tropical forest ecosystems. By using Neobalanocarpus heimii (Dipterocarpaceae) as an example, the study assessed the feasibility of using short tandem repeats (STRs) as a tool to identify the source of illegally logged timber. Thirty natural populations of N. heimii were profiled using 12 STRs to develop the DNA profiling databases. As the cluster analysis divided the 30 populations into three genetic clusters, corresponding to three subregions within Peninsular Malaysia. The DNA databases were characterised at the levels of population, subregion and Peninsular Malaysia. Independence tests within and among loci were violated in all the databases due to significant levels of population differentiation and inbreeding. Thus, the effects of population substructure and inbreeding should be incorporated into the calculation of random match probability. The random match probabilities estimated using subpopulation and subpopulation-cum-inbreeding models were biased in favour of the defendant, whereas the random match probabilities estimated using product rule were biased in favour of the prosecutor. The conservativeness tests showed that the subregion and Peninsular Malaysia databases were conservative, and these databases should be able to provide legal evidence for court proceedings against illegal loggers in Peninsular Malaysia

X-ray protection, surface chemistry and rheology of ball-milled submicron Gd2O3 aqueous suspension

X-ray protective garments are typically comprised of lead-based materials, which are toxic to both people and the environment. Developing alternative lightweight radiation shielding materials is a priority for protecting people working with radiation. Gadolinium, with an electron configuration typical of radiation shielding elements, is proposed as a non-toxic replacement for lead. This study provides new insights into the potential for a gadolinium suspension for replacing lead and proposes an inexpensive and effective preparation method. Submicron gadolinium oxide (Gd2O3) was generated using a cost effective ball milling method involving addition of NaCl. Then, the dispersed-flocculated behaviour of Gd2O3 aqueous slurries was studied via yield stress and zeta potential techniques to stabilise the dispersion. The relationship of the transmission-volume fraction at different kVp from an interventional radiology source was established to investigate radiation attenuation performance of the suspension. At a low volume fraction (0.082), the gadolinium slurry attenuated more than 95% of the X-ray load from a 50⬜100 kVp source. The equivalent weight-thickness at the same attenuation of 95% (5% transmission) of the Gd2O3 suspension was 1.5 g/cm2, which is comparable to that of equivalent commercial lead-based materials (\u3e1 g/cm2). This research is significant for developing a non-lead-based material, Gd2O3 suspension, which offers effective radiation attenuation with weight-thickness minimisation and safe use and disposal

Highly variable STR markers of Neobalanocarpus heimii (Dipterocarpaceae) for forensic DNA profiling

Neobalanocarpus heimii, locally known as chengal, is an important timber species in Peninsular Malaysia. Owing to the high demand for its valuable timber, N. heimii is subjected to illegal logging and this species may become endangered in the near future. The present study was designed to identify a set of highly polymorphic short tandem repeat (STR) markers for timber tracking of N. heimii. An extensive evaluation of 51 STRs developed for Dipterocarpaceae managed to identify 12 STR loci (Nhe004, Nhe005, Nhe011, Nhe015, Nhe018, Hbi161, Sle392, Sle605, Slu044a, Shc03, Shc04 and Shc07), which showed specific amplification, high polymorphism, single-locus mode of inheritance, absence of null alleles and absence of mononucleotide repeat motifs in N. heimii. These loci can be readily used to establish a linkage between the evidentiary sample and the source, thus providing a useful set of markers for individual identification in N. heimii

SPDF: Sparse Pre-training and Dense Fine-tuning for Large Language Models

The pre-training and fine-tuning paradigm has contributed to a number of breakthroughs in Natural Language Processing (NLP). Instead of directly training on a downstream task, language models are first pre-trained on large datasets with cross-domain knowledge (e.g., Pile, MassiveText, etc.) and then fine-tuned on task-specific data (e.g., natural language generation, text summarization, etc.). Scaling the model and dataset size has helped improve the performance of LLMs, but unfortunately, this also lead to highly prohibitive computational costs. Pre-training LLMs often require orders of magnitude more FLOPs than fine-tuning and the model capacity often remains the same between the two phases. To achieve training efficiency w.r.t training FLOPs, we propose to decouple the model capacity between the two phases and introduce Sparse Pre-training and Dense Fine-tuning (SPDF). In this work, we show the benefits of using unstructured weight sparsity to train only a subset of weights during pre-training (Sparse Pre-training) and then recover the representational capacity by allowing the zeroed weights to learn (Dense Fine-tuning). We demonstrate that we can induce up to 75% sparsity into a 1.3B parameter GPT-3 XL model resulting in a 2.5x reduction in pre-training FLOPs, without a significant loss in accuracy on the downstream tasks relative to the dense baseline. By rigorously evaluating multiple downstream tasks, we also establish a relationship between sparsity, task complexity and dataset size. Our work presents a promising direction to train large GPT models at a fraction of the training FLOPs using weight sparsity, while retaining the benefits of pre-trained textual representations for downstream tasks.Comment: Accepted to Uncertainty in Artificial Intelligence (UAI) 2023 Conference; 13 pages, 4 figures (Main Paper) + 5 pages (Supplementary Material