Monash University

About: Monash University is a education organization based out in Melbourne, Victoria, Australia. It is known for research contribution in the topics: Population & Poison control. The organization has 35920 authors who have published 100681 publications receiving 3027002 citations.

Optimized Design of Stationary Frame Three Phase AC Current Regulators

Abstract: Current regulation plays an important role in modern power electronic AC conversion systems The most direct strategy to regulate such currents is to use a simple closed loop proportional-integral (PI) regulator, which has no theoretical stability limits as the proportional and integral gains are increased, since it is only a second order system However, pulsewidth modulation (PWM) transport and controller sampling delays limit the gain values that can be achieved in practical systems Taking these limitations into account, this paper presents an analytical method to determine the best possible gains that can be achieved for any class of practical linear AC current controller The analysis shows that the maximum possible proportional gain is determined by the plant series inductance, the DC bus voltage and the transport and sampling delays, while the maximum possible integral gain is determined primarily by the transport and sampling delays The work is applicable to stationary frame PI regulators, stationary frame controllers with back electromotive force compensation, stationary frame P+ resonant (PR) controllers, and synchronous d- q frame controllers, since they all have identical proportional and integral gains that must be optimized for any particular application

Adverse effects of biologics: a network meta‐analysis and Cochrane overview

Abstract: Background Biologics are used for the treatment of rheumatoid arthritis and many other conditions. While the efficacy of biologics has been established, there is uncertainty regarding the adverse effects of this treatment. Since serious risks such as tuberculosis (TB) reactivation, serious infections, and lymphomas may be common to the biologics but occur in small numbers across the various indications, we planned to combine the results from biologics used in many conditions to obtain the much needed risk estimates. Objectives To compare the adverse effects of tumor necrosis factor blocker (etanercept, adalimumab, infliximab, golimumab, certolizumab), interleukin (IL)-1 antagonist (anakinra), IL-6 antagonist (tocilizumab), anti-CD28 (abatacept), and anti-B cell (rituximab) therapy in patients with any disease condition except human immunodeficiency disease (HIV/AIDS). Methods Randomized controlled trials (RCTs), controlled clinical trials (CCTs) and open-label extension (OLE) studies that studied one of the nine biologics for use in any indication (with the exception of HIV/AIDS) and that reported our pre-specified adverse outcomes were considered for inclusion. We searched The Cochrane Library, MEDLINE, and EMBASE (to January 2010). Identifying search results and data extraction were performed independently and in duplicate. For the network meta-analysis, we performed mixed-effects logistic regression using an arm-based, random-effects model within an empirical Bayes framework. Main results We included 163 RCTs with 50,010 participants and 46 extension studies with 11,954 participants. The median duration of RCTs was six months and 13 months for OLEs. Data were limited for tuberculosis (TB) reactivation, lymphoma, and congestive heart failure. Adjusted for dose, biologics as a group were associated with a statistically significant higher rate of total adverse events (odds ratio (OR) 1.19, 95% CI 1.09 to 1.30; number needed to treat to harm (NNTH) = 30, 95% CI 21 to 60) and withdrawals due to adverse events (OR 1.32, 95% CI 1.06 to 1.64; NNTH = 37, 95% CI 19 to 190) and an increased risk of TB reactivation (OR 4.68, 95% CI 1.18 to 18.60; NNTH = 681, 95% CI 143 to 14706) compared to control.The rate of serious adverse events, serious infections, lymphoma, and congestive heart failure were not statistically significantly different between biologics and control treatment. Certolizumab pegol was associated with significantly higher risk of serious infections compared to control treatment (OR 3.51, 95% CI 1.59 to 7.79; NNTH = 17, 95% CI 7 to 68). Infliximab was associated with significantly higher risk of withdrawals due to adverse events compared to control (OR 2.04, 95% CI 1.43 to 2.91; NNTH = 12, 95% CI 8 to 28). Indirect comparisons revealed that abatacept and anakinra were associated with a significantly lower risk of serious adverse events compared to most other biologics. Although the overall numbers are relatively small, certolizumab pegol was associated with significantly higher odds of serious infections compared to etanercept, adalimumab, abatacept, anakinra, golimumab, infliximab, and rituximab; abatacept was significantly less likely than infliximab and tocilizumab to be associated with serious infections. Abatacept, adalimumab, etanercept and golimumab were significantly less likely than infliximab to result in withdrawals due to adverse events. Authors' conclusions Overall, in the short term biologics were associated with significantly higher rates of total adverse events, withdrawals due to adverse events and TB reactivation. Some biologics had a statistically higher association with certain adverse outcomes compared to control, but there was no consistency across the outcomes so caution is needed in interpreting these results.There is an urgent need for more research regarding the long-term safety of biologics and the comparative safety of different biologics. National and international registries and other types of large databases are relevant sources for providing complementary evidence regarding the short- and longer-term safety of biologics.

A comparison of the analgesic efficacy and side-effects of paravertebral vs epidural blockade for thoracotomy—a systematic review and meta-analysis of randomized trials

Abstract: Epidural analgesia is considered by many to be the best method of pain relief after major surgery. It is used routinely in many thoracic surgery centres. Although effective, side-effects include hypotension, urinary retention, incomplete (or failed) block, and, in rare cases, paraplegia. Paravertebral block (PVB) is an alternative technique that may offer comparable analgesic effectiveness and a better side-effect profile. We undertook a systematic review and meta-analysis of all relevant randomized trials comparing PVB with epidural analgesia in thoracic surgery. Data were abstracted and verified by both authors. Studies were tested for heterogeneity, and meta-analyses were done with random effects or fixed effects models. Weighted mean difference (WMD) was used for numerical outcomes and odds ratio (OR) for dichotomous outcomes, both with 95% CI. We identified 10 trials that had enrolled 520 thoracic surgery patients. All of the trials were small (n

Genome analysis of the platypus reveals unique signatures of evolution

Abstract: We present a draft genome sequence of the platypus, Ornithorhynchus anatinus This monotreme exhibits a fascinating combination of reptilian and mammalian characters For example, platypuses have a coat of fur adapted to an aquatic lifestyle; platypus females lactate, yet lay eggs; and males are equipped with venom similar to that of reptiles Analysis of the first monotreme genome aligned these features with genetic innovations We find that reptile and platypus venom proteins have been co-opted independently from the same gene families; milk protein genes are conserved despite platypuses laying eggs; and immune gene family expansions are directly related to platypus biology Expansions of protein, non-protein-coding RNA and microRNA families, as well as repeat elements, are identified Sequencing of this genome now provides a valuable resource for deep mammalian comparative analyses, as well as for monotreme biology and conservation

Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes

Abstract: Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57-1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628-0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs.