An Open-Label Pilot Study Testing the Feasibility of Assessing Total Symptom Burden in Trials of Cannabinoid Medications in Palliative Care.

Background: There is considerable interest in the use of cannabinoids for symptom control in palliative care, but there is little high-quality evidence to guide clinical practice. Objectives: Assess the feasibility of using global symptom burden measures to assess response to medicinal cannabis, to determine median tolerated doses of cannabidiol (CBD) and tetrahydrocannabinol (THC), and to document adverse events (AEs). Design: Prospective two-arm open-label pilot trial of escalating doses of CBD and THC oil. Setting/Subjects: Participants had advanced cancer and cancer-related symptoms in a palliative and supportive care service in an Australian cancer center. Measurements: The main outcome measures were the number of participants screened and randomized over the time frame, the number of participants completing days 14 and 28 and providing total symptom distress scores (TSDSs) (measured using the Edmonton Symptom Assessment Scale), and the change from baseline of the TSDS at day 14. Results: Of the 21 participants enrolled (CBD, n = 16; THC, n = 5), 18 (86%) completed the primary outcome measure at day 14 and 8 completed at day 28. The median maximum tolerated doses were CBD, 300 mg/day (range 100-600 mg); THC, 10 mg/day (range 5-30 mg). Nine of 21 patients (43%) met the definition of response (≥6 point reduction in TSDS). Drowsiness was the most common AE. Conclusions: Trials of medicinal cannabis in advanced cancer patients undergoing palliative care are feasible. The doses of THC and CBD used in this study were generally well tolerated and the outcome measure of total symptom distress is promising as a measure of overall symptom benefit. Trial registration: ACTRN12618001205224

Postoperative outcomes associated with surgical care for women in Africa: an international risk-adjusted analysis of prospective observational cohorts

Background: Improving women's health is a critical component of the sustainable development goals. Although obstetric outcomes in Africa have received significant focus, non-obstetric surgical outcomes for women in Africa remain under-examined. Methods: We did a secondary analysis of the African Surgical Outcomes Study (ASOS) and International Surgical Outcomes Study (ISOS), two 7-day prospective observational cohort studies of outcomes after adult inpatient surgery. This sub-study focuses specifically on the analysis of the female, elective, non-obstetric, non-gynaecological surgical data collected during these two large multicentre studies. The African data from both cohorts are compared with international (non-African) outcomes in a risk-adjusted logistic regression analysis using a generalised linear mixed-effects model. The primary outcome was severe postoperative complications including in-hospital mortality in Africa compared with non-African outcomes. Results: A total of 1698 African participants and 18 449 international participants met the inclusion criteria. The African cohort were younger than the international cohort with a lower preoperative risk profile. Severe complications occurred in 48 (2.9%) of 1671, and 431 (2.3%) of 18 449 patients in the African and international cohorts, respectively, with in-hospital mortality after severe complications of 23/48 (47.9%) in Africa and 78/431 (18.1%) internationally. Women in Africa had an adjusted odds ratio of 2.06 (95% confidence interval, 1.17–3.62; P=0.012) of developing a severe postoperative complication after elective non-obstetric, non-gynaecological surgery, compared with the international cohort. Conclusions: Women in Africa have double the risk adjusted odds of severe postoperative complications (including in-hospital mortality) after elective non-obstetric, non-gynaecological surgery compared with the international incidence

Phytochemical Assays of Commercial Botanical Dietary Supplements

The growing popularity of botanical dietary supplements (BDS) has been accompanied by concerns regarding the quality of commercial products. Health care providers, in particular, have an interest in knowing about product quality, in view of the issues related to herb-drug interactions and potential side effects. This study assessed whether commercial formulations of saw palmetto, kava kava, echinacea, ginseng and St. John's wort had consistent labeling and whether quantities of marker compounds agreed with the amounts stated on the label. We purchased six bottles each of two lots of supplements from nine manufacturers and analyzed the contents using established commercial methodologies at an independent laboratory. Product labels were found to vary in the information provided, such as serving recommendations and information about the herb itself (species, part of the plant, marker compound, etc.) With regard to marker compound content, little variability was observed between different lots of the same brand, while the content did vary widely between brands (e.g. total phenolic compounds in Echinacea ranged from 3.9–15.3 mg per serving; total ginsenosides in ginseng ranged from 5.3–18.2 mg per serving). Further, the amounts recommended for daily use also differed between brands, increasing the potential range of a consumer's daily dose. Echinacea and ginseng were the most variable, while St. John's wort and saw palmetto were the least variable. This study highlights some of the key issues in the botanical supplement market, including the importance of standardized manufacturing practices and reliable labeling information. In addition, health care providers should keep themselves informed regarding product quality in order to be able to appropriately advise patients utilizing both conventional and herbal medicines

A Genome-wide gene-expression analysis and database in transgenic mice during development of amyloid or tau pathology

We provide microarray data comparing genome-wide differential expression and pathology throughout life in four lines of "amyloid" transgenic mice (mutant human APP, PSEN1, or APP/PSEN1) and "TAU" transgenic mice (mutant human MAPT gene). Microarray data were validated by qPCR and by comparison to human studies, including genome-wide association study (GWAS) hits. Immune gene expression correlated tightly with plaques whereas synaptic genes correlated negatively with neurofibrillary tangles. Network analysis of immune gene modules revealed six hub genes in hippocampus of amyloid mice, four in common with cortex. The hippocampal network in TAU mice was similar except that Trem2 had hub status only in amyloid mice. The cortical network of TAU mice was entirely different with more hub genes and few in common with the other networks, suggesting reasons for specificity of cortical dysfunction in FTDP17. This Resource opens up many areas for investigation. All data are available and searchable at http://www.mouseac.org

The mixed problem for the Laplacian in Lipschitz domains

We consider the mixed boundary value problem or Zaremba's problem for the Laplacian in a bounded Lipschitz domain in R^n. We specify Dirichlet data on part of the boundary and Neumann data on the remainder of the boundary. We assume that the boundary between the sets where we specify Dirichlet and Neumann data is a Lipschitz surface. We require that the Neumann data is in L^p and the Dirichlet data is in the Sobolev space of functions having one derivative in L^p for some p near 1. Under these conditions, there is a unique solution to the mixed problem with the non-tangential maximal function of the gradient of the solution in L^p of the boundary. We also obtain results with data from Hardy spaces when p=1.Comment: Version 5 includes a correction to one step of the main proof. Since the paper appeared long ago, this submission includes the complete paper, followed by a short section that gives the correction to one step in the proo

Clarifying Assumptions about Intraoperative Stress during Surgical Performance: More Than a Stab in the Dark: Reply

Ó The Author(s) 2011. This article is published with open access at Springerlink.com We thank Dr. Ali for his concise annotation of our efforts to validate a tool that evaluates mental workload in surgery [1, 2]. Unlike other safety critical domains, the field of surgery has been slow to acknowledge the impact of intraoperative stress on surgical performance, but recently a sea change has been triggered by authorities in the field of surgical education [3]. We agree with Ali that stress is not by default detrimental to performance. Our aim was to develop a diagnostic tool that identifies the factors that contribute to disrupted performance, should it occur. Indeed, studies of the effects of acute stress on operating performance have shown considerable variability, ranging from no effect to either facilitative or debilitative effects [3–5]. The Yerkes-Dodson law emerged from the earliest attempts to explain the relationship between physiological arousal and performance, but it has been criticized for treating stress as a unitary construct, influenced solely by physiological factors [6]. More recently, Catastrophe Theory has been invoked to model the relationship, using both physiological and psychological (cognitive anxiety) components of stress [7]. The model proposes that physiological arousal displays a mild inverted-U relationship with performance when cognitive anxiety is low, but that catastrophic declines in performance can occur if both physiological arousal and cognitive anxiety are high. Recent surgical literature has elucidated the complexity of M. Wilson (&

Relationship between temporomandibular joint dynamics and mouthguards: feasibility of a test method

A test system was developed establishing the feasibility of collecting biomechanical data as they relate to the use of mouthguards. Previous experimental studies have examined the physical and mechanical properties of mouthguard materials. This information has been used as a guide for establishing material standards and specifications for the fabrication of mouthguards, but it lacks the key biomechanical parameters required for a thorough mouthguard evaluation. The current study was designed to assess whether the impact force, condylar deflection, and strain superior to the temporomandibular joint region could be measured. A drop test was conducted on a cadaveric specimen to simulate loading at the chin point. To measure the force of impact, an accelerometer was attached to an impactor of known mass. High-speed biplanar (1000 frames per second) radiographs were used to determine condylar displacement. Radio-opaque markers were inserted into the bone at predetermined locations. Total displacement of these markers was determined in reference to anatomical landmarks. Strain gauges were attached to the mandible and skull to monitor the effects of the condyle impacting the base of the skull. Based on the data collected, forces were calculated by determining the product of the time-based acceleration and known mass. A measurable change in force between the mouthguards and the control (no mouthguard) was demonstrated. The average condylar displacement was successfully measured and indicated as an increase in total deflection for impacts conducted with mouthguards. Quantifiable strain was measured in the region above the mandibular fossa with and without the insertion of a mouthguard at all impact conditions. However, it was determined that additional gauges would provide critical data. Key biomechanical parameters for chin-point impacts were determined in the current study. The technique demonstrated that both displacement within the mandibular fossa and loading of the condyles occur during the impact event. Although the current study established a technique that can be used to examine the relationship between mouthguards and jaw-joint injuries, the role, if any, mouthguards play in the reduction of injuries cannot be established until a thorough analysis is completed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74031/1/j.1600-9657.2004.00213.x.pd

A precision study of the fine tuning in the DiracNMSSM

Recently the DiracNMSSM has been proposed as a possible solution to reduce the fine tuning in supersymmetry. We determine the degree of fine tuning needed in the DiracNMSSM with and without non-universal gaugino masses and compare it with the fine tuning in the GNMSSM. To apply reasonable cuts on the allowed parameter regions we perform a precise calculation of the Higgs mass. In addition, we include the limits from direct SUSY searches and dark matter abundance. We find that both models are comparable in terms of fine tuning, with the minimal fine tuning in the GNMSSM slightly smaller.Comment: 20 pages + appendices, 10 figure

Consistent phenological shifts in the making of a biodiversity hotspot: the Cape flora

Background The best documented survival responses of organisms to past climate change on short (glacial-interglacial) timescales are distributional shifts. Despite ample evidence on such timescales for local adaptations of populations at specific sites, the long-term impacts of such changes on evolutionary significant units in response to past climatic change have been little documented. Here we use phylogenies to reconstruct changes in distribution and flowering ecology of the Cape flora - South Africa's biodiversity hotspot - through a period of past (Neogene and Quaternary) changes in the seasonality of rainfall over a timescale of several million years. Results Forty-three distributional and phenological shifts consistent with past climatic change occur across the flora, and a comparable number of clades underwent adaptive changes in their flowering phenology (9 clades; half of the clades investigated) as underwent distributional shifts (12 clades; two thirds of the clades investigated). Of extant Cape angiosperm species, 14-41% have been contributed by lineages that show distributional shifts consistent with past climate change, yet a similar proportion (14-55%) arose from lineages that shifted flowering phenology. Conclusions Adaptive changes in ecology at the scale we uncover in the Cape and consistent with past climatic change have not been documented for other floras. Shifts in climate tolerance appear to have been more important in this flora than is currently appreciated, and lineages that underwent such shifts went on to contribute a high proportion of the flora's extant species diversity. That shifts in phenology, on an evolutionary timescale and on such a scale, have not yet been detected for other floras is likely a result of the method used; shifts in flowering phenology cannot be detected in the fossil record