Showing papers by "Monash University published in 2012"

Guidelines for the use and interpretation of assays for monitoring autophagy

Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.

Validation of the theoretical domains framework for use in behaviour change and implementation research

Abstract: An integrative theoretical framework, developed for cross-disciplinary implementation and other behaviour change research, has been applied across a wide range of clinical situations. This study tests the validity of this framework. Validity was investigated by behavioural experts sorting 112 unique theoretical constructs using closed and open sort tasks. The extent of replication was tested by Discriminant Content Validation and Fuzzy Cluster Analysis. There was good support for a refinement of the framework comprising 14 domains of theoretical constructs (average silhouette value 0.29): ‘Knowledge’, ‘Skills’, ‘Social/Professional Role and Identity’, ‘Beliefs about Capabilities’, ‘Optimism’, ‘Beliefs about Consequences’, ‘Reinforcement’, ‘Intentions’, ‘Goals’, ‘Memory, Attention and Decision Processes’, ‘Environmental Context and Resources’, ‘Social Influences’, ‘Emotions’, and ‘Behavioural Regulation’. The refined Theoretical Domains Framework has a strengthened empirical base and provides a method for theoretically assessing implementation problems, as well as professional and other health-related behaviours as a basis for intervention development.

A systematic review of the global prevalence of low back pain

Abstract: Objective To perform a systematic review of the global prevalence of low back pain, and to examine the influence that case definition, prevalence period, and other variables have on prevalence. Methods We conduced a new systematic review of the global prevalence of low back pain that included general population studies published between 1980 and 2009. A total of 165 studies from 54 countries were identified. Of these, 64% had been published since the last comparable review. Results Low back pain was shown to be a major problem throughout the world, with the highest prevalence among female individuals and those aged 40–80 years. After adjusting for methodologic variation, the mean ± SEM point prevalence was estimated to be 11.9 ± 2.0%, and the 1-month prevalence was estimated to be 23.2 ± 2.9%. Conclusion As the population ages, the global number of individuals with low back pain is likely to increase substantially over the coming decades. Investigators are encouraged to adopt recent recommendations for a standard definition of low back pain and to consult a recently developed tool for assessing the risk of bias of prevalence studies.

A Double-Blind, Placebo-Controlled Trial of Ruxolitinib for Myelofibrosis

Abstract: A B S T R AC T background Ruxolitinib, a selective inhibitor of Janus kinase (JAK) 1 and 2, has clinically significant activity in myelofibrosis. methodS In this double-blind trial, we randomly assigned patients with intermediate-2 or highrisk myelofibrosis to twice-daily oral ruxolitinib (155 patients) or placebo (154 patients). The primary end point was the proportion of patients with a reduction in spleen volume of 35% or more at 24 weeks, assessed by means of magnetic resonance imaging. Secondary end points included the durability of response, changes in symptom burden (assessed by the total symptom score), and overall survival. resulTS The primary end point was reached in 41.9% of patients in the ruxolitinib group as compared with 0.7% in the placebo group (P<0.001). A reduction in spleen volume was maintained in patients who received ruxolitinib; 67.0% of the patients with a response had the response for 48 weeks or more. There was an improvement of 50% or more in the total symptom score at 24 weeks in 45.9% of patients who received ruxolitinib as compared with 5.3% of patients who received placebo (P<0.001). Thirteen deaths occurred in the ruxolitinib group as compared with 24 deaths in the placebo group (hazard ratio, 0.50; 95% confidence interval, 0.25 to 0.98; P = 0.04). The rate of discontinuation of the study drug because of adverse events was 11.0% in the ruxolitinib group and 10.6% in the placebo group. Among patients who received ruxolitinib, anemia and thrombocytopenia were the most common adverse events, but they rarely led to discontinuation of the drug (in one patient for each event). Two patients had transformation to acute myeloid leukemia; both were in the ruxolitinib group. conclusionS Ruxolitinib, as compared with placebo, provided significant clinical benefits in patients with myelofibrosis by reducing spleen size, ameliorating debilitating myelofibrosis-related symptoms, and improving overall survival. These benefits came at the cost of more frequent anemia and thrombocytopenia in the early part of the treatment period. (Funded by Incyte; COMFORT-I ClinicalTrials.gov number, NCT00952289.)

The Proprioceptive Senses: Their Roles in Signaling Body Shape, Body Position and Movement, and Muscle Force

Abstract: This is a review of the proprioceptive senses generated as a result of our own actions. They include the senses of position and movement of our limbs and trunk, the sense of effort, the sense of force, and the sense of heaviness. Receptors involved in proprioception are located in skin, muscles, and joints. Information about limb position and movement is not generated by individual receptors, but by populations of afferents. Afferent signals generated during a movement are processed to code for endpoint position of a limb. The afferent input is referred to a central body map to determine the location of the limbs in space. Experimental phantom limbs, produced by blocking peripheral nerves, have shown that motor areas in the brain are able to generate conscious sensations of limb displacement and movement in the absence of any sensory input. In the normal limb tendon organs and possibly also muscle spindles contribute to the senses of force and heaviness. Exercise can disturb proprioception, and this has implications for musculoskeletal injuries. Proprioceptive senses, particularly of limb position and movement, deteriorate with age and are associated with an increased risk of falls in the elderly. The more recent information available on proprioception has given a better understanding of the mechanisms underlying these senses as well as providing new insight into a range of clinical conditions.

Isolation-Based Anomaly Detection

Abstract: Anomalies are data points that are few and different. As a result of these properties, we show that, anomalies are susceptible to a mechanism called isolation. This article proposes a method called Isolation Forest (iForest), which detects anomalies purely based on the concept of isolation without employing any distance or density measure---fundamentally different from all existing methods.As a result, iForest is able to exploit subsampling (i) to achieve a low linear time-complexity and a small memory-requirement and (ii) to deal with the effects of swamping and masking effectively. Our empirical evaluation shows that iForest outperforms ORCA, one-class SVM, LOF and Random Forests in terms of AUC, processing time, and it is robust against masking and swamping effects. iForest also works well in high dimensional problems containing a large number of irrelevant attributes, and when anomalies are not available in training sample.

Prevalence and determinants of common perinatal mental disorders in women in low- and lower-middle-income countries: a systematic review

Abstract: OBJECTIVE: To review the evidence about the prevalence and determinants of non-psychotic common perinatal mental disorders (CPMDs) in World Bank categorized low- and lower-middle-income countries. METHODS: Major databases were searched systematically for English-language publications on the prevalence of non-psychotic CPMDs and on their risk factors and determinants. All study designs were included. FINDINGS: Thirteen papers covering 17 low- and lower-middle-income countries provided findings for pregnant women, and 34, for women who had just given birth. Data on disorders in the antenatal period were available for 9 (8%) countries, and on disorders in the postnatal period, for 17 (15%). Weighted mean prevalence was 15.6% (95% confidence interval, CI: 15.4-15.9) antenatally and 19.8% (19.5-20.0) postnatally. Risk factors were: socioeconomic disadvantage (odds ratio [OR] range: 2.1-13.2); unintended pregnancy (1.6-8.8); being younger (2.1-5.4); being unmarried (3.4-5.8); lacking intimate partner empathy and support (2.0-9.4); having hostile in-laws (2.1-4.4); experiencing intimate partner violence (2.11-6.75); having insufficient emotional and practical support (2.8-6.1); in some settings, giving birth to a female (1.8-2.6), and having a history of mental health problems (5.1-5.6). Protective factors were: having more education (relative risk: 0.5; P = 0.03); having a permanent job (OR: 0.64; 95% CI: 0.4-1.0); being of the ethnic majority (OR: 0.2; 95% CI: 0.1-0.8) and having a kind, trustworthy intimate partner (OR: 0.52; 95% CI: 0.3-0.9). CONCLUSION: CPMDs are more prevalent in low- and lower-middle-income countries, particularly among poorer women with gender-based risks or a psychiatric history.

Breaking Up Prolonged Sitting Reduces Postprandial Glucose and Insulin Responses

Abstract: OBJECTIVE Observational studies show breaking up prolonged sitting has beneficial associations with cardiometabolic risk markers, but intervention studies are required to investigate causality. We examined the acute effects on postprandial glucose and insulin levels of uninterrupted sitting compared with sitting interrupted by brief bouts of light- or moderate-intensity walking. RESEARCH DESIGN AND METHODS Overweight/obese adults ( n = 19), aged 45–65 years, were recruited for a randomized three-period, three-treatment acute crossover trial: 1 ) uninterrupted sitting; 2 ) seated with 2-min bouts of light-intensity walking every 20 min; and 3 ) seated with 2-min bouts of moderate-intensity walking every 20 min. A standardized test drink was provided after an initial 2-h period of uninterrupted sitting. The positive incremental area under curves (iAUC) for glucose and insulin (mean [95% CI]) for the 5 h after the test drink (75 g glucose, 50 g fat) were calculated for the respective treatments. RESULTS The glucose iAUC (mmol/L) ⋅ h after both activity-break conditions was reduced (light: 5.2 [4.1–6.6]; moderate: 4.9 [3.8–6.1]; both P P CONCLUSIONS Interrupting sitting time with short bouts of light- or moderate-intensity walking lowers postprandial glucose and insulin levels in overweight/obese adults. This may improve glucose metabolism and potentially be an important public health and clinical intervention strategy for reducing cardiovascular risk.

Developing theory-informed behaviour change interventions to implement evidence into practice: a systematic approach using the Theoretical Domains Framework

Abstract: There is little systematic operational guidance about how best to develop complex interventions to reduce the gap between practice and evidence. This article is one in a Series of articles documenting the development and use of the Theoretical Domains Framework (TDF) to advance the science of implementation research. The intervention was developed considering three main components: theory, evidence, and practical issues. We used a four-step approach, consisting of guiding questions, to direct the choice of the most appropriate components of an implementation intervention: Who needs to do what, differently? Using a theoretical framework, which barriers and enablers need to be addressed? Which intervention components (behaviour change techniques and mode(s) of delivery) could overcome the modifiable barriers and enhance the enablers? And how can behaviour change be measured and understood? A complex implementation intervention was designed that aimed to improve acute low back pain management in primary care. We used the TDF to identify the barriers and enablers to the uptake of evidence into practice and to guide the choice of intervention components. These components were then combined into a cohesive intervention. The intervention was delivered via two facilitated interactive small group workshops. We also produced a DVD to distribute to all participants in the intervention group. We chose outcome measures in order to assess the mediating mechanisms of behaviour change. We have illustrated a four-step systematic method for developing an intervention designed to change clinical practice based on a theoretical framework. The method of development provides a systematic framework that could be used by others developing complex implementation interventions. While this framework should be iteratively adjusted and refined to suit other contexts and settings, we believe that the four-step process should be maintained as the primary framework to guide researchers through a comprehensive intervention development process.

Association Between a Chloride-Liberal vs Chloride-Restrictive Intravenous Fluid Administration Strategy and Kidney Injury in Critically Ill Adults

Abstract: Context Administration of traditional chloride-liberal intravenous fluids may precipitate acute kidney injury (AKI). Objective To assess the association of a chloride-restrictive (vs chloride-liberal) intravenous fluid strategy with AKI in critically ill patients. Design, Setting, and Patients Prospective, open-label, sequential period pilot study of 760 patients admitted consecutively to the intensive care unit (ICU) during the control period (February 18 to August 17, 2008) compared with 773 patients admitted consecutively during the intervention period (February 18 to August 17, 2009) at a university-affiliated hospital in Melbourne, Australia. Interventions During the control period, patients received standard intravenous fluids. After a 6-month phase-out period (August 18, 2008, to February 17, 2009), any use of chloride-rich intravenous fluids (0.9% saline, 4% succinylated gelatin solution, or 4% albumin solution) was restricted to attending specialist approval only during the intervention period; patients instead received a lactated solution (Hartmann solution), a balanced solution (Plasma-Lyte 148), and chloride-poor 20% albumin. Main Outcome Measures The primary outcomes included increase from baseline to peak creatinine level in the ICU and incidence of AKI according to the risk, injury, failure, loss, end-stage (RIFLE) classification. Secondary post hoc analysis outcomes included the need for renal replacement therapy (RRT), length of stay in ICU and hospital, and survival. Results Chloride administration decreased by 144 504 mmol (from 694 to 496 mmol/patient) from the control period to the intervention period. Comparing the control period with the intervention period, the mean serum creatinine level increase while in the ICU was 22.6 μmol/L (95% CI, 17.5-27.7 μmol/L) vs 14.8 μmol/L (95% CI, 9.8-19.9 μmol/L) (P = .03), the incidence of injury and failure class of RIFLE-defined AKI was 14% (95% CI, 11%-16%; n = 105) vs 8.4% (95% CI, 6.4%-10%; n = 65) (P Conclusion The implementation of a chloride-restrictive strategy in a tertiary ICU was associated with a significant decrease in the incidence of AKI and use of RRT. Trial Registration clinicaltrials.gov Identifier: NCT00885404

Averting biodiversity collapse in tropical forest protected areas

Abstract: The rapid disruption of tropical forests probably imperils global biodiversity more than any other contemporary phenomenon(1-3). With deforestation advancing quickly, protected areas are increasingly becoming final refuges for threatened species and natural ecosystem processes. However, many protected areas in the tropics are themselves vulnerable to human encroachment and other environmental stresses(4-9). As pressures mount, it is vital to know whether existing reserves can sustain their biodiversity. A critical constraint in addressing this question has been that data describing a broad array of biodiversity groups have been unavailable for a sufficiently large and representative sample of reserves. Here we present a uniquely comprehensive data set on changes over the past 20 to 30 years in 31 functional groups of species and 21 potential drivers of environmental change, for 60 protected areas stratified across the world's major tropical regions. Our analysis reveals great variation in reserve 'health': about half of all reserves have been effective or performed passably, but the rest are experiencing an erosion of biodiversity that is often alarmingly widespread taxonomically and functionally. Habitat disruption, hunting and forest-product exploitation were the strongest predictors of declining reserve health. Crucially, environmental changes immediately outside reserves seemed nearly as important as those inside in determining their ecological fate, with changes inside reserves strongly mirroring those occurring around them. These findings suggest that tropical protected areas are often intimately linked ecologically to their surrounding habitats, and that a failure to stem broad-scale loss and degradation of such habitats could sharply increase the likelihood of serious biodiversity declines.

Health Care Customer Value Cocreation Practice Styles

Abstract: This article explores in-depth what health care customers actually do when they cocreate value. Combining previously published research with data collected from depth interviews, field observation,...

Aliskiren, ALTITUDE, and the implications for ATMOSPHERE

Abstract: Blockade of the renin–angiotensin system (RAS) is a core therapeutic strategy in systolic heart failure.1 The value of angiotensin-converting enzyme (ACE) inhibitors was proven in two pivotal trials conducted >20 years ago. More recently, angiotensin receptor blockers (ARBs) have also been shown to be beneficial in systolic heart failure both as an alternative to and when added to an ACE inhibitor. Separately, mineralocorticoid receptor antagonists (MRAs) reduce mortality and morbidity when added to an ACE inhibitor or ARB (MRAs are not considered further here). The latest approach to RAS blockade to be tested in clinical practice is renin inhibition. Currently the efficacy and safety of the renin inhibitor aliskiren is being tested in two clinical trials in heart failure, the Aliskiren Trial of Minimizing OutcomeS for Patients with HEart failure (ATMOSPHERE) and the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT), described previously in this journal.2,3 However, on 20 December 2011, treatment in another study, the Aliskiren Trial In Type 2 Diabetes Using Cardio-Renal Disease Endpoints (ALTITUDE), was stopped on the recommendation of its Data Monitoring Committee (DMC).2,3 ALTITUDE was comparing placebo or aliskiren 300 mg once daily, added to background ACE inhibitor or ARB therapy in patients with diabetes and either (i) increased urinary albumin excretion or (ii) both a reduced estimated glomerular filtration rate (eGFR 30–60 mL/min/1.73 m2) and established cardiovascular disease. The primary outcome in ALTITUDE is a composite of cardiovascular death, resuscitated sudden death, non-fatal myocardial infarction, non-fatal stroke, unplanned hospitalization for heart failure, end-stage renal disease, renal death, or doubling of baseline serum creatinine concentration, sustained for at least a month. As a result of the DMC recommendation, ALTITUDE is currently being closed out in an orderly fashion. The basis of the DMC recommendation was futility (i.e. no prospect of demonstrating the treatment benefit anticipated in the protocol) as well as safety concerns. These concerns included renal dysfunction, hyperkalaemia, and hypotension (which are unsurprising) as well as an excess of strokes. In the publically released information, the number of patients experiencing a non-fatal stroke in the placebo group was 85 (2.0%) and 112 (2.6%) in the aliskiren group (nominal, unadjusted, P-value 0.04).6 Although this unexpected finding has provoked concern and discussion, the reported numbers do not represent the final number of events in ALTITUDE (at the time of the DMC's recommendation it was estimated that approximately a third of events remained to be collected and adjudicated). Consequently, while the apparent imbalance in strokes may persist or increase, it may also attenuate. Furthermore, given all prior data relating use of antihypertensive therapy to a reduced incidence of stroke in patients with diabetes, it is also possible that the imbalance in strokes represents a chance finding.7–9 In response to these findings it has been recommended that dual aliskiren and ACE inhibitor/ARB therapy not be used in patients with both hypertension (the current indication for aliskiren) and diabetes or moderate to severe renal dysfunction (eGFR <60 mL/min/1.73 m2).10 This recommendation has led to questions about the use of dual aliskiren therapy in patients with diabetes in the ongoing ATMOSPHERE trial (and, to a lesser extent, also the ASTRONAUT trial which has almost finished recruitment and will complete follow-up this year). In ATMOSPHERE, patients with systolic heart failure and an elevated B-type natriuretic peptide (BNP) or N-terminal pro BNP ( NT-proBNP) concentration are randomized in equal proportions to receive either enalapril 10 mg twice daily, aliskiren 300 mg once daily, or the combination of both drugs.3 ATMOSPHERE is an event-driven trial with a primary composite outcome of cardiovascular death or heart failure hospitalization. We believe that the preliminary results of ALTITUDE should not lead to any alteration in the conduct of ATMOSPHERE. The reasons for taking this view are discussed in detail below.

Vestibular migraine: diagnostic criteria

Abstract: This paper presents diagnostic criteria for vestibular migraine, jointly formulated by the Committee for Classification of Vestibular Disorders of the Barany Society and the Migraine Classification Subcommittee of the International Headache Society (IHS) The classification includes vestibular migraine and probable vestibular migraine Vestibular migraine will appear in an appendix of the third edition of the International Classification of Headache Disorders (ICHD) as a first step for new entities, in accordance with the usual IHS procedures Probable vestibular migraine may be included in a later version of the ICHD, when further evidence has been accumulated The diagnosis of vestibular migraine is based on recurrent vestibular symptoms, a history of migraine, a temporal association between vestibular symptoms and migraine symptoms and exclusion of other causes of vestibular symptoms Symptoms that qualify for a diagnosis of vestibular migraine include various types of vertigo as well as head motion-induced dizziness with nausea Symptoms must be of moderate or severe intensity Duration of acute episodes is limited to a window of between 5 minutes and 72 hours

Continuous Lenalidomide Treatment for Newly Diagnosed Multiple Myeloma

Abstract: The median follow-up period was 30 months. The median progression-free survival was significantly longer with MPR-R (31 months) than with MPR (14 months; hazard ratio, 0.49; P<0.001) or MP (13 months; hazard ratio, 0.40; P <0.001). Response rates were superior with MPR-R and MPR (77% and 68%, respectively, vs. 50% with MP; P<0.001 and P = 0.002, respectively, for the comparison with MP). The progression-free survival benefit associated with MPR-R was noted in patients 65 to 75 years of age but not in those older than 75 years of age (P = 0.001 for treatment-by-age interaction). After induction therapy, a landmark analysis showed a 66% reduction in the rate of progression with MPR-R (hazard ratio for the comparison with MPR, 0.34; P<0.001) that was age-independent. During induction therapy, the most frequent adverse events were hematologic; grade 4 neutropenia was reported in 35%, 32%, and 8% of the patients in the MPR-R, MPR, and MP groups, respectively. The 3-year rate of second primary tumors was 7% with MPR-R, 7% with MPR, and 3% with MP. Conclusions MPR-R significantly prolonged progression-free survival in patients with newly di agnosed multiple myeloma who were ineligible for transplantation, with the great est benefit observed in patients 65 to 75 years of age. (Funded by Celgene; MM-015 ClinicalTrials.gov number, NCT00405756.)

Association of LDL Cholesterol, Non–HDL Cholesterol, and Apolipoprotein B Levels With Risk of Cardiovascular Events Among Patients Treated With Statins: A Meta-analysis

Abstract: Context The associations of low-density lipoprotein cholesterol (LDL-C), non–high-density lipoprotein cholesterol (non–HDL-C), and apolipoprotein B (apoB) levels with the risk of cardiovascular events among patients treated with statin therapy have not been reliably documented. Objective To evaluate the relative strength of the associations of LDL-C, non–HDL-C, and apoB with cardiovascular risk among patients treated with statin therapy. Design Meta-analysis of individual patient data from randomized controlled statin trials in which conventional lipids and apolipoproteins were determined in all study participants at baseline and at 1-year follow-up. Data Sources Relevant trials were identified by a literature search updated through December 31, 2011. Investigators were contacted and individual patient data were requested and obtained for 62 154 patients enrolled in 8 trials published between 1994 and 2008. Data Extraction Hazard ratios (HRs) and corresponding 95% CIs for risk of major cardiovascular events adjusted for established risk factors by 1-SD increase in LDL-C, non–HDL-C, and apoB. Results Among 38 153 patients allocated to statin therapy, 158 fatal myocardial infarctions, 1678 nonfatal myocardial infarctions, 615 fatal events from other coronary artery disease, 2806 hospitalizations for unstable angina, and 1029 fatal or nonfatal strokes occurred during follow-up. The adjusted HRs for major cardiovascular events per 1-SD increase were 1.13 (95% CI, 1.10-1.17) for LDL-C, 1.16 (95% CI, 1.12-1.19) for non–HDL-C, and 1.14 (95% CI, 1.11-1.18) for apoB. These HRs were significantly higher for non–HDL-C than LDL-C (P = .002) and apoB (P = .02). There was no significant difference between apoB and LDL-C (P = .21). Conclusion Among statin-treated patients, on-treatment levels of LDL-C, non–HDL-C, and apoB were each associated with risk of future major cardiovascular events, but the strength of this association was greater for non–HDL-C than for LDL-C and apoB.

Smoothed Particle Hydrodynamics and Its Diverse Applications

Abstract: This review focuses on the applications of smoothed particle hydrodynamics (SPH) to incompressible or nearly incompressible flow. In the past 17 years, the range of applications has increased as researchers have realized the ability of SPH algorithms to handle complex physical problems. These include the disruption of free surfaces when a wave hits a rocky beach, multifluid problems that may involve the motion of rigid and elastic bodies, non-Newtonian fluids, virtual surgery, and chemical precipitation from fluids moving through fractured media. SPH provides a fascinating tool that has some of the properties of molecular dynamics while retaining the attributes of the macroscopic equations of continuum mechanics.

The Star Formation Rate of Turbulent Magnetized Clouds: Comparing Theory, Simulations, and Observations

Abstract: The role of turbulence and magnetic fields is studied for star formation in molecular clouds. We derive and compare six theoretical models for the star formation rate (SFR)—the Krumholz & McKee (KM), Padoan & Nordlund (PN), and Hennebelle & Chabrier (HC) models, and three multi-freefall versions of these, suggested by HC—all based on integrals over the log-normal distribution of turbulent gas. We extend all theories to include magnetic fields and show that the SFR depends on four basic parameters: (1) virial parameter αvir; (2) sonic Mach number ; (3) turbulent forcing parameter b, which is a measure for the fraction of energy driven in compressive modes; and (4) plasma with the Alfven Mach number . We compare all six theories with MHD simulations, covering cloud masses of 300 to 4 × 106 M ☉ and Mach numbers -50 and -∞, with solenoidal (b = 1/3), mixed (b = 0.4), and compressive turbulent (b = 1) forcings. We find that the SFR increases by a factor of four between and 50 for compressive turbulent forcing and αvir ~ 1. Comparing forcing parameters, we see that the SFR is more than 10 times higher with compressive than solenoidal forcing for simulations. The SFR and fragmentation are both reduced by a factor of two in strongly magnetized, trans-Alfvenic turbulence compared to hydrodynamic turbulence. All simulations are fit simultaneously by the multi-freefall KM and multi-freefall PN theories within a factor of two over two orders of magnitude in SFR. The simulated SFRs cover the range and correlation of SFR column density with gas column density observed in Galactic clouds, and agree well for star formation efficiencies SFE = 1%-10% and local efficiencies = 0.3-0.7 due to feedback. We conclude that the SFR is primarily controlled by interstellar turbulence, with a secondary effect coming from magnetic fields.

Towards an HIV cure: a global scientific strategy

Abstract: Given the limitations of antiretroviral therapy and recent advances in our understanding of HIV persistence during effective treatment, there is a growing recognition that a cure for HIV infection is both needed and feasible. The International AIDS Society convened a group of international experts to develop a scientific strategy for research towards an HIV cure. Several priorities for basic, translational and clinical research were identified. This Opinion article summarizes the group's recommended key goals for the international community.

Nanoencapsulation of food ingredients using lipid based delivery systems

Abstract: Nanoencapsulation allows protection of the sensitive bioactive food ingredients from unfavorable environmental conditions, eradication of incompatibilities, solubilization, or masking of unpleasant taste or odor. This paper reviews the present state of the art of lipid based carriers including nanoemulsions, nanoliposomes, solid lipid nanoparticles (SLNs) and novel generation of encapsulation system namely nanostructure lipid carriers (NLCs) regarding their production method, physicochemical properties, functionalities, stabilization techniques, potential advantages and limitations and delivery mechanisms. In the last section, mathematical models for predication of bioactive release kinetics from lipid based nanocarriers, which can be applied for optimization of encapsulation systems, are presented and some future developments in the area of nanoencapsulation are discussed.