FastICARL: Fast incremental classifier and representation learning with efficient budget allocation in audio sensing applications

Various incremental learning (IL) approaches have been proposed to help deep learning models learn new tasks/classes continuously without forgetting what was learned previously (i.e., avoid catastrophic forgetting). With the growing number of deployed audio sensing applications that need to dynamically incorporate new tasks and changing input distribution from users, the ability of IL on-device becomes essential for both efficiency and user privacy. However, prior works suffer from high computational costs and storage demands which hinders the deployment of IL on-device. In this work, to overcome these limitations, we develop an end-to-end and on-device IL framework, FastICARL, that incorporates an exemplar-based IL and quantization in the context of audio-based applications. We first employ k-nearest-neighbor to reduce the latency of IL. Then, we jointly utilize a quantization technique to decrease the storage requirements of IL. We implement FastICARL on two types of mobile devices and demonstrate that FastICARL remarkably decreases the IL time up to 78-92% and the storage requirements by 2-4 times without sacrificing its performance. FastICARL enables complete on-device IL, ensuring user privacy as the user data does not need to leave the device

UBR2 of the N-end rule pathway is required for chromosome stability via histone ubiquitylation in spermatocytes and somatic cells

The N-end rule pathway is a proteolytic system in which its recognition components (N-recognins) recognize destabilizing N-terminal residues of short-lived proteins as an essential element of specific degrons, called N-degrons. The RING E3 ligases UBR2 and UBR1 are major N-recognins that share size (200 kDa), conserved domains and substrate specificities to N-degrons. Despite the known function of the N-end rule pathway in degradation of cytosolic proteins, the major phenotype of UBR2-deficient male mice is infertility caused by arrest of spermatocytes at meiotic prophase I. UBR2-deficient spermatocytes are impaired in transcriptional silencing of sex chromosome-linked genes and ubiquitylation of histone H2A. In this study we show that the recruitment of UBR2 to meiotic chromosomes spatiotemporally correlates to the induction of chromatin-associated ubiquitylation, which is significantly impaired in UBR2-deficient spermatocytes. UBR2 functions as a scaffold E3 that promotes HR6B/UbcH2-dependent ubiquitylation of H2A and H2B but not H3 and H4, through a mechanism distinct from typical polyubiquitylation. The E3 activity of UBR2 in histone ubiquitylation is allosterically activated by dipeptides bearing destabilizing N-terminal residues. Insufficient monoubiquitylation and polyubiquitylation on UBR2-deficient meiotic chromosomes correlate to defects in double strand break (DSB) repair and other meiotic processes, resulting in pachytene arrest at stage IV and apoptosis. Some of these functions of UBR2 are observed in somatic cells, in which UBR2 is a chromatin-binding protein involved in chromatin-associated ubiquitylation upon DNA damage. UBR2-deficient somatic cells show an array of chromosomal abnormalities, including hyperproliferation, chromosome instability, and hypersensitivity to DNA damage-inducing reagents. UBR2-deficient mice enriched in C57 background die upon birth with defects in lung expansion and neural development. Thus, UBR2, known as the recognition component of a major cellular proteolytic system, is associated with chromatin and controls chromatin dynamics and gene expression in both germ cells and somatic cells. © 2012 Kwon et al

Acupuncture for pain and osteoarthritis of the knee: a pilot study for an open parallel-arm randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>There is some evidence that acupuncture for pain and osteoarthritis (OA) of the knee is more than a placebo, and short term clinical benefits have been observed when acupuncture is compared to usual care. However there is insufficient evidence on whether clinical benefits of acupuncture are sustained over the longer term. In this study our key objectives are to inform the design parameters for a fully powered pragmatic randomised controlled trial. These objectives include establishing potential recruitment rates, appropriate validated outcome measures, attendance levels for acupuncture treatment, loss to follow up and the sample size for a full scale trial.</p> <p>Methods</p> <p>Potential participants aged over 50 with pain and osteoarthritis of the knee were identified from a GP database. Eligible patients were randomised to either 'acupuncture plus usual care' and 'usual care' alone, with allocation appropriately concealed. Acupuncture consisted of up to 10 sessions usually weekly. Outcome measures included Western Ontario and McMaster Universities (WOMAC) index with the sample size for a full scale trial determined from the variance.</p> <p>Results</p> <p>From the GP database of 15,927 patients, 335 potential trial participants were identified and invited to participate. After screening responses, 78 (23%) were identified as eligible and 30 patients who responded most promptly were randomised to 'acupuncture plus usual care' (15 patients) and 'usual care' alone (15 patients). Attendance for acupuncture appointments was high at 90% of the maximum. Although the trial was not powered to detect significant changes in outcome, the WOMAC pain index showed a statistically significant reduction at 3 months in the acupuncture group compared to usual care. This was not sustained at 12 months. The sample size for a fully powered two-arm trial was estimated to be 350.</p> <p>Conclusion</p> <p>This pilot study provided the evidence that a fully powered study to explore the longer term impact of acupuncture would be worthwhile, and relevant design features for such a trial were determined.</p> <p>Trial registration number</p> <p>ISRCTN25134802.</p

The effect of acupuncture duration on analgesia and peripheral sensory thresholds

<p>Abstract</p> <p>Background</p> <p>Acupuncture provides a means of peripheral stimulation for pain relief. However, the detailed neuronal mechanisms by which acupuncture relieves pain are still poorly understood and information regarding optimal treatment settings is still inadequate. Previous studies with a short burst of unilateral electroacupuncture (EA) in the Tendinomuscular Meridians (TMM) treatment model for pain demonstrated a transient dermatomally correlated bilateral analgesic effect with corresponding peripheral modality-specific sensory threshold alterations. However, the impact of EA duration on the analgesic effect in this particular treatment model is unknown. To obtain mechanistically and clinically important information regarding EA analgesia, this current prospective cross-over study assesses the effects of EA duration on analgesia and thermal sensory thresholds in the TMM treatment model.</p> <p>Methods</p> <p>Baseline peripheral sensory thresholds were measured at pre-marked testing sites along the medial aspects (liver and spleen meridians) of bilateral lower extremities. A 5-second hot pain stimulation was delivered to the testing sites and the corresponding pain Visual Analog Scale (VAS) scores were recorded. Three different EA (5Hz) stimulation durations (5, 15 and 30 minutes) were randomly tested at least one week apart. At the last 10 seconds of each EA session, 5 seconds of subject specific HP stimulation was delivered to the testing sites. The corresponding pain and EA VAS scores of de qi sensation (tingling) during and after the EA were recorded. The measurements were repeated immediately, 30 and 60 minutes after the EA stimulation. A four-factor repeat measures ANOVA was used to assess the effect of stimulation duration, time, location (thigh vs. calf) and side (ipsilateral vs. contralateral) of EA on sensory thresholds and HP VAS scores.</p> <p>Results</p> <p>A significant (P < 0.01) main effect of time and location with warm, cold and hot pain thresholds at the four testing sites without any significant difference in duration effect was observed. Similar time and location effects were observed with HP VAS with the longer durations (15 and 30 minutes) of stimulation showed a slower onset, but a more sustainable bilateral analgesic benefit than the short stimulation duration (5 minutes). The 15-minute stimulation resulted in an earlier onset of analgesic effect than the 30-minute stimulation paradigm.</p> <p>Conclusion</p> <p>Longer durations of EA stimulation provide a more sustainable analgesic benefit to hot noxious stimulation than a shorter duration of stimulation. The increase of cold threshold with sustained warm threshold temperature elevation as observed in the longer durations of EA suggests that as the duration of EA lengthened, there is a gradual shifting from an initial predominantly spinally mediated analgesic effect to a supraspinally mediated modulatory mechanism of thermal pain. The 15-minute stimulation appeared to be the optimal setting for treating acute pain in the lower extremities.</p

Acupuncture in the treatment of rheumatoid arthritis: a double-blind controlled pilot study

<p>Abstract</p> <p>Background</p> <p>In planning a randomized controlled trial of acupuncture, we conducted a pilot study using validated outcome measures to assess the feasibility of the protocol, and to obtain preliminary data on efficacy and tolerability of 3 different forms of acupuncture treatment as an adjunct for the treatment of chronic pain in patients with Rheumatoid arthritis (RA).</p> <p>Methods</p> <p>The study employs a randomized, prospective, double-blind, placebo-controlled trial to evaluate the effect of electroacupuncture (EA), traditional Chinese acupuncture (TCA) and sham acupuncture (Sham) in patients with RA. All patients received 20 sessions over a period of 10 weeks. Six acupuncture points were chosen. Primary outcome is the changes in the pain score. Secondary outcomes included the changes in the ACR core disease measures, DAS 28 score and the number of patients who achieved ACR 20 at week 10.</p> <p>Results</p> <p>From 80 eligible patients, 36 patients with mean age of 58 ± 10 years and disease duration of 9.3 ± 6.4 years were recruited. Twelve patients were randomized to each group. Twelve, 10 and 7 patients from the EA, TCA and Sham group respectively completed the study at 20 weeks (p < 0.03); all except one of the premature dropouts were due to lack of efficacy. At week 10, the pain score remained unchanged in all 3 groups. The number of tender joints was significantly reduced for the EA and TCA groups. Physician's global score was significantly reduced for the EA group and patient's global score was significantly reduced for the TCA group. All the outcomes except patient's global score remained unchanged in the Sham group.</p> <p>Conclusion</p> <p>This pilot study has allowed a number of recommendations to be made to facilitate the design of a large-scale trial, which in turn will help to clarify the existing evidence base on acupuncture for RA.</p> <p>Trial registration</p> <p>ClinicalTrials.gov NCT00404443</p

Herbal remedy clinical trials in the media: a comparison with the coverage of conventional pharmaceuticals

<p>Abstract</p> <p>Background</p> <p>This study systematically compares newspaper coverage of clinical trials for herbal remedies, a popular type of complementary and alternative medicine, with clinical trials for pharmaceuticals using a comparative content analysis. This is a timely inquiry given the recognized importance of the popular press as a source of health information, the complex and significant role of complementary and alternative medicine in individual health-care decisions, and the trend toward evidence-based research for some complementary and alternative medical therapies. We searched PubMed for clinical trials, Lexis/Nexis for newspaper articles in the UK, US, Australia/New Zealand, and Factiva for Canadian newspaper articles from 1995 to 2005. We used a coding frame to analyze and compare 48 pharmaceutical and 57 herbal remedy clinical trials as well as 201 pharmaceutical and 352 herbal remedy newspaper articles.</p> <p>Results</p> <p>Herbal remedy clinical trials had similar Jadad scores to pharmaceutical trials but were significantly smaller and of shorter duration. The trials were mostly studies from Western countries and published in high-ranking journals. The majority of pharmaceutical (64%) and herbal remedy (53%) clinical trials had private sector funding involvement. A minority declared further author conflicts of interest. Newspaper coverage of herbal remedy clinical trials was more negative than for pharmaceutical trials; a result only partly explained by the greater proportion of herbal remedy clinical trials reporting negative results (<it>P </it>= 0.0201; <it>χ</it>²= 7.8129; degrees of freedom = 2). Errors of omission were common in newspaper coverage, with little reporting of dose, sample size, location, and duration of the trial, methods, trial funding, and conflicts of interest. There was an under-reporting of risks, especially for herbal remedies.</p> <p>Conclusion</p> <p>Our finding of negative coverage of herbal remedy trials is contrary to the positive trends in most published research based primarily on anecdotal accounts. Our results highlight how media coverage is not providing the public with the information necessary to make informed decisions about medical treatments. Most concerning is the lack of disclosure of trial funding and conflicts of interest that could influence the outcome or reporting of trial results. This lack of reporting may impact the medical research community, which has the most to lose by way of public trust and respect.</p

Development of a Bead-Based Multiplex Genotyping Method for Diagnostic Characterization of HPV Infection

The accurate genotyping of human papillomavirus (HPV) is clinically important because the oncogenic potential of HPV is dependent on specific genotypes. Here, we described the development of a bead-based multiplex HPV genotyping (MPG) method which is able to detect 20 types of HPV (15 high-risk HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68 and 5 low-risk HPV types 6, 11, 40, 55, 70) and evaluated its accuracy with sequencing. A total of 890 clinical samples were studied. Among these samples, 484 were HPV positive and 406 were HPV negative by consensus primer (PGMY09/11) directed PCR. The genotyping of 484 HPV positive samples was carried out by the bead-based MPG method. The accuracy was 93.5% (95% CI, 91.0–96.0), 80.1% (95% CI, 72.3–87.9) for single and multiple infections, respectively, while a complete type mismatch was observed only in one sample. The MPG method indiscriminately detected dysplasia of several cytological grades including 71.8% (95% CI, 61.5–82.3) of ASCUS (atypical squamous cells of undetermined significance) and more specific for high grade lesions. For women with HSIL (high grade squamous intraepithelial lesion) and SCC diagnosis, 32 women showed a PPV (positive predictive value) of 77.3% (95% CI, 64.8–89.8). Among women >40 years of age, 22 women with histological cervical cancer lesions showed a PPV of 88% (95% CI, 75.3–100). Of the highest risk HPV types including HPV-16, 18 and 31 positive women of the same age groups, 34 women with histological cervical cancer lesions showed a PPV of 77.3% (95% CI, 65.0–89.6). Taken together, the bead-based MPG method could successfully detect high-grade lesions and high-risk HPV types with a high degree of accuracy in clinical samples