Non-aqueous Isorefractive Pickering Emulsions

Non-aqueous Pickering emulsions of 16–240 μm diameter have been prepared using diblock copolymer worms with ethylene glycol as the droplet phase and an n-alkane as the continuous phase. Initial studies using n-dodecane resulted in stable emulsions that were significantly less turbid than conventional water-in-oil emulsions. This is attributed to the rather similar refractive indices of the latter two phases. By utilizing n-tetradecane as an alternative oil that almost precisely matches the refractive index of ethylene glycol, almost isorefractive ethylene glycol-in-n-tetradecane Pickering emulsions can be prepared. The droplet diameter and transparency of such emulsions can be systematically varied by adjusting the worm copolymer concentration

Estimating treatment effects for individual patients based on the results of randomised clinical trials

Objectives To predict treatment effects for individual patients based on data from randomised trials, taking rosuvastatin treatment in the primary prevention of cardiovascular disease as an example, and to evaluate the net benefit of making treatment decisions for individual patients based on a predicted absolute treatment effect

Recurrent venous thromboembolism and bleeding with extended anticoagulation: the VTE-PREDICT risk score

Aims Deciding to stop or continue anticoagulation for venous thromboembolism (VTE) after initial treatment is challenging, as individual risks of recurrence and bleeding are heterogeneous. The present study aimed to develop and externally validate models for predicting 5-year risks of recurrence and bleeding in patients with VTE without cancer who completed at least 3 months of initial treatment, which can be used to estimate individual absolute benefits and harms of extended anticoagulation. Methods and results Competing risk-adjusted models were derived to predict recurrent VTE and clinically relevant bleeding (non-major and major) using 14 readily available patient characteristics. The models were derived from combined individual patient data from the Bleeding Risk Study, Hokusai-VTE, PREFER-VTE, RE-MEDY, and RE-SONATE (n = 15,141, 220 recurrences, 189 bleeding events). External validity was assessed in the Danish VTE cohort, EINSTEIN-CHOICE, GARFIELD-VTE, MEGA, and Tromsø studies (n = 59 257, 2283 recurrences, 3335 bleeding events). Absolute treatment effects were estimated by combining the models with hazard ratios from trials and meta-analyses. External validation in different settings showed agreement between predicted and observed risks up to 5 years, with C-statistics ranging from 0.48–0.71 (recurrence) and 0.61–0.68 (bleeding). In the Danish VTE cohort, 5-year risks ranged from 4% to 19% for recurrent VTE and 1% –19% for bleeding. Conclusion The VTE-PREDICT risk score can be applied to estimate the effect of extended anticoagulant treatment for individual patients with VTE and to support shared decision-making

Predicting motor outcome and quality of life after subthalamic deep brain stimulation for Parkinson's disease: the role of standard screening measures and wearable data

Background:Standardized screening for subthalamic deep brain stimulation (STN DBS) in Parkinson’s disease (PD) patients is crucial to determine eligibility, but its utility to predict postoperative outcomes in eligible patients is inconclusive. It is unknown whether wearable data can contribute to this aim.Objective:To evaluate the utility of universal components incorporated in the DBS screening, complemented by a wearable sensor, to predict motor outcomes and Quality of life (QoL) one year after STN DBS surgery.Methods:Consecutive patients were included in the OPTIMIST cohort study from two DBS centers. Standardized assessments included a preoperative Levodopa Challenge Test (LCT), and questionnaires on QoL and non-motor symptoms including cognition, psychiatric symptoms, impulsiveness, autonomic symptoms, and sleeping problems. Moreover, an ambulatory wearable sensor (Parkinson Kinetigraph (PKG)) was used. Postoperative assessments were similar and also included a Stimulation Challenge Test to determine DBS effects on motor function.Results:Eighty-three patients were included (median (interquartile range) age 63 (56–68) years, 36% female). Med-OFF (Stim-OFF) motor severity deteriorated indicating disease progression, but patients significantly improved in terms of Med-ON (Stim-ON) motor function, motor fluctuations, QoL, and most non-motor domains. Motor outcomes were not predicted by preoperative tests, including covariates of either LCT or PKG. Postoperative QoL was predicted by better preoperative QoL, lower age, and more preoperative impulsiveness scores in multivariate models.Conclusion:Data from the DBS screening including wearable data do not predict postoperative motor outcome at one year. Post-DBS QoL appears primarily driven by non-motor symptoms, rather than by motor improvement.Scientific Assessment and Innovation in Neurosurgical Treatment Strategie

Effects of external irradiation of the neck region on intima media thickness of the common carotid artery

<p>Abstract</p> <p>Background</p> <p>Several studies have shown that common carotid intima-media thickness (IMT) is increased after radiotherapy (RT) to the head and neck. However, further studies are needed to define the exact mechanism of radiation-induced injury in large vessels, investigate the relationship between radiation dose and large vessel injury and evaluate the rate of progress of atherosclerosis in irradiated vessels.</p> <p>Objectives</p> <p>To investigate whether external irradiation to the carotid area has any effect on IMT of the common carotid artery in a group of patients who received RT vs control group matched for age, gender and race.</p> <p>Methods</p> <p>We studied 19 patients (10 male; 47.8 ± 17.4 years) during a 5-month period (January 2009-July 2009); they had completed RT with a mean of 2.9 years before (range: 1 month-6 years) The mean radiation dose to the neck in the irradiated patients was 41.2 ± 15.6 Gy (range: 25-70 Gy). Common carotid IMT was measured with echo-color Doppler. Nineteen healthy adult patients (10 male; 47.8 ± 17.6) were recruited as a control group.</p> <p>Results</p> <p>IMT was not significantly higher in patients when compared to the control group (0.59 ± 0.16 vs 0.56 ± 0.16 mm, p = 0.4). There was no significant difference between the two groups in relation to the absence (p = 0.7) or presence (p = 0.6) of vascular risk factors. Although the difference did not reach statistical significance (p = 0.1), the irradiated young patients (age ≤ 52 years) had IMT measurements higher (0.54 ± 0.08 mm) than the non-irradiated young patients (0.49 ± 0.14 mm). The mean carotid IMT increased with increasing doses of radiation to the neck (p = 0.04).</p> <p>Conclusion</p> <p>This study shows that increased IMT of the common carotid artery after RT is radiation-dose-related. Therefore it is important to monitor IMT, which can be used as an imaging biomarker for early diagnosis of cerebrovascular disease in patients who have had radiotherapy for treatment of cancer of the head and neck and who are at increased risk for accelerated atherosclerosis in carotid arteries.</p

Patients' Experience of therapeutic footwear whilst living at risk of neuropathic diabetic foot ulceration: an interpretative phenomenological analysis (IPA).

BACKGROUND: Previous work has found that people with diabetes do not wear their therapeutic footwear as directed, but the thinking behind this behaviour is unclear. Adherence to therapeutic footwear advice must improve in order to reduce foot ulceration and amputation risk in people with diabetes and neuropathy. Therefore this study aimed to explore the psychological influences and personal experiences behind the daily footwear selection of individuals with diabetes and neuropathy. METHODS: An interpretative phenomenological analysis (IPA) approach was used to explore the understanding and experience of therapeutic footwear use in people living at risk of diabetic neuropathic foot ulceration. This study benefited from the purposive selection of a small sample of four people and used in-depth semi structured interviews because it facilitated the deep and detailed examination of personal thoughts and feelings behind footwear selection. FINDINGS: Four overlapping themes that interact to regulate footwear choice emerged from the analyses: a) Self-perception dilemma; resolving the balance of risk experienced by people with diabetes and neuropathy day to day, between choosing to wear footwear to look and feel normal and choosing footwear to protect their feet from foot ulceration; b) Reflective adaption; The modification and individualisation of a set of values about footwear usage created in the minds of people with diabetes and neuropathy; c) Adherence response; The realignment of footwear choice with personal values, to reinforce the decision not to change behaviour or bring about increased footwear adherence, with or without appearance management; d) Reality appraisal; A here and now appraisal of the personal benefit of footwear choice on emotional and physical wellbeing, with additional consideration to the preservation of therapeutic footwear. CONCLUSION: For some people living at risk of diabetic neuropathic foot ulceration, the decision whether or not to wear therapeutic footwear is driven by the individual 'here and now', risks and benefits, of footwear choice on emotional and physical well-being for a given social context

The effects of hypertonic fluid administration on the gene expression of inflammatory mediators in circulating leucocytes in patients with septic shock: a preliminary study

Contains fulltext : 98426.pdf (publisher's version ) (Open Access)ABSTRACT: OBJECTIVE: This study was designed to investigate the effect of hypertonic fluid administration on inflammatory mediator gene expression in patients with septic shock. DESIGN AND SETTING: Prospective, randomized, controlled, double-blind clinical study in a 15-bed mixed intensive care unit in a tertiary referral teaching hospital. INTERVENTIONS: Twenty-four patients, who met standard criteria for septic shock, were randomized to receive a bolus of hypertonic fluid (HT, 250 ml 6% HES/7.2% NaCl) or isotonic fluid (IT, 500 ml 6% HES/0.9% NaCl) administered over 15 minutes. Randomization and study fluid administration was within 24 hours of ICU admission for all patients. This trial is registered with ANZCTR.org.au as ACTRN12607000259448. RESULTS: Blood samples were taken immediately before and 4, 8, 12, and 24 hours after fluid administration. Real-time reverse transcriptase polymerase chain reaction (RT rtPCR) was used to quantify mRNA expression of different inflammatory mediators in peripheral leukocytes. In the HT group, compared with the IT group, levels of gene expression of MMP9 and L-selectin were significantly suppressed (p = 0.0002 and p = 0.007, respectively), and CD11b gene expression tended to be elevated (p = NS). No differences were found in the other mediators examined. CONCLUSIONS: In septic shock patients, hypertonic fluid administration compared with isotonic fluid may modulate expression of genes that are implicated in leukocyte-endothelial interaction and capillary leakage.The study was performed at the Intensive Care Department, Waikato Hospital, and at the Molecular Genetics Laboratory, University of Waikato, Hamilton, New Zealand. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12607000259448

Whey-based diet containing medium chain triglycerides modulates the gut microbiota and protects the intestinal mucosa from chemotherapy while maintaining therapy efficacy.

Cytotoxicity (i.e. cell death) is the core mechanism by which chemotherapy induces its anti-cancer effects. Unfortunately, this same mechanism underpins the collateral damage it causes to healthy tissues. The gastrointestinal tract is highly susceptible to chemotherapy’s cytotoxicity, resulting in ulcerative lesions (termed gastrointestinal mucositis, GI-M) that impair the functional capacity of the gut leading to diarrhea, anorexia, malnutrition and weight loss, which negatively impact physical/psychological wellbeing and treatment adherence. Preventing these side effects has proven challenging given the overlapping mechanisms that dictate chemotherapy efficacy and toxicity. Here, we report on a novel dietary intervention that, due to its localized gastrointestinal effects, is able to protect the intestinal mucosal from unwanted toxicity without impairing the anti-tumor effects of chemotherapy. The test diet (containing extensively hydrolyzed whey protein and medium chain triglycerides (MCTs)), was investigated in both tumor-naïve and tumor-bearing models to evaluate its effect on GI-M and chemo-efficacy, respectively. In both models, methotrexate was used as the representative chemotherapeutic agent and the diet was provided ad libitum for 14 days prior to treatment. GI-M was measured using the validated biomarker plasma citrulline, and chemo-efficacy defined by tumor burden (cm3 /g body weight). The test diet significantly attenuated GI-M (P = 0.03), with associated reductions in diarrhea (P < 0.0001), weight loss (P < 0.05), daily activity (P < 0.02) and maintenance of body composition (P < 0.02). Moreover, the test diet showed significant impact on gut microbiota by increasing diversity and resilience, whilst also altering microbial composition and function (indicated by cecal short and brained chain fatty acids). The test diet did not impair the efficacy of methotrexate against mammary adenocarcinoma (tumor) cells. In line with the first model, the test diet minimized intestinal injury (P = 0.001) and diarrhea (P < 0.0001). These data support translational initiatives to determine the clinical feasibility, utility and efficacy of this diet to improve chemotherapy treatment outcomes.Hannah R. Wardill, Ana Rita Da Silva Ferreira, Himanshu Kumar, Emma H. Bateman, Courtney B. Cross, Joanne M. Bowen, Rick Havinga, Hermie J. M. Harmsen, Jan Knol, Bram Dorresteijn, Miriam van Dijk, Jeroen van Bergenhenegouwen, and Wim J. E. Tissin

Acoustic risk balancing by marine mammals : anthropogenic noise can influence the foraging decisions by seals

Funding: Natural Environment Research Council (Grant Number(s): NE/J004251/1, NE/R015007/1)1. Avoidance of anthropogenic sounds has been measured in many species. The results, which are typically based on observations in limited exposure contexts, are frequently used to inform policy and the regulation of industrial activities. However, the occurrence and magnitude of avoidance may be a consequence of complex risk-balancing decisions made by animals. The importance of the factors in decision-making, such as perceived risks associated with the sounds or prey quantity and quality during sound exposure, is unknown. 2. Here we address this knowledge gap by measuring the relative influence of perceived –risk of a sound (silence, pile driving, and a tidal turbine) and prey patch quality on decision-making and foraging success in grey seals Halichoerus grypus. 3. Seals were given access to two underwater ‘prey patches’ in an experimental pool where fish were delivered at controlled rates to simulate a low-density (LD) and a high-density (HD) prey patch. Acoustic playbacks were made using an underwater speaker above one of the prey patches (randomised during the study), and three decision and foraging metrics (foraging duration, foraging effort allocation between the prey patches, and foraging success) were measured. 4. Foraging success was highest during silent controls and was similar regardless of speaker location (LD/HD). Under the tidal turbine and pile-driving treatments, foraging success was similar to the controls when the speaker was located at the HD prey patch but was significantly reduced (~16%–28% lower) when the speaker was located at the LD prey patch. Foraging decisions by the seals were consistent with a risk/profit balancing approach. Avoidance rates depend on the quality of the prey patch as well as the perceived risk. 5. Policy implications. The results suggest that foraging context is important when interpreting avoidance behaviour and should be considered when predicting the effects of anthropogenic activities. For example, sound exposure in different prey patch qualities may result in markedly different avoidance behaviour, potentially leading to contrasting predictions of impact in Environmental Assessments. We recommend future studies explicitly consider foraging context, and other contextual factors such as behavioural state (e.g. foraging or travelling) and habitat quality.Publisher PDFPeer reviewe