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Despite considerable academic attention to the role of family caregivers within the general population, little research has been conducted with Indigenous families. This qualitative study aims to fill that gap by focusing on the experiences of Metis caregivers providing care for older Metis adults. Focus groups and interviews were conducted with Metis family caregivers (n = 79), Metis Elders (n = 11) and formal caregivers (n = 8). Although there are considerable parallels in the caregiving experiences identified in this Metis study with those already documented in the literature, there are nonetheless important differences for providing culturally responsive care to Metis seniors.
This is a copy of the slides presented at the meeting but not formally
written up for the volume.
In the past four decades lipid vesicles (liposomes) have evolved from
widely used biomembrane models into important drug and gene carriers. The
phosphatidylcholine phospholipids PC used in the drug carriers are
biocompatible and biodegradable but they function as a relatively inert
shell and require the incorporation of cholesterol to maintain the drug
encapsulated in the liposome; The PC are also incapable of associating
with ligands and have very weak interactions with nucleic acids.
Moreover, they are not particularly good for cytoplasmic delivery of the
encapsulated cargo. Recently, we have devised three classes of new lipids
and have improved the synthesis of a fourth class that enable the
preparation of a bioresponsive targeted carrier with improved nucleic
acid delivery. Class 1 are low pH sensitive and include a diortho ester
PEG lipid or a di-orthoester PC. Class two are redox sensitive lipids and
include thiocholesterol based and thio diacyl chain based lipids that can
be used in a sequential assembly process to encapsulate nucleic acid
drugs in a charge neutral or negatively charged nanolipid particle. Class
3 is a new family of lipids that provide increased in vivo bilayer
stability without the need for crosslinking of the bilayer. Class 4 is an
improved synthesis of a triNTA diacyl lipid. This lipid can be used to
attach His-6 containing molecules to the bilayer vesicle after the
liposomes have been prepared and loaded with drugs. These lipids form a
tool kit that can be used to prepare a variety of targeted drug, protein
and nucleic acid delivery vesicles with attached targeting ligands. The
synthesis, characterization and use of these lipids in a variety of drug
delivery applications will be described. Suported by NIH EB003008 &
We evaluated the relationship between food availability, as the only dietary exposure data available across Africa, and age-standardised cancer incidence rates (ASR) in eighteen countries.
Availability of food groups and dietary energy was considered for five hypothetical time points: years of collection of ASR (T0) and 5, 10, 15 and 20 preceding years (T–5, T–10, T–15, T–20). Ecological correlations adjusted for human development index, smoking and obesity rates were calculated to evaluate the relationship between food availability and ASR of breast, prostate, colorectal, oesophageal, pancreatic, stomach and thyroid cancer.
Red meat was positively correlated with pancreatic cancer in men (T–20: r–20 = 0·61, P < 0·05), stomach cancer in women (T0: r0 = 0·58, P < 0·05), and colorectal cancer in men (T0: r0 = 0·53, P < 0·05) and women (T–20: r–20 = 0·58, P < 0·05). Animal products including meat, animal fats and higher animal-sourced energy supply tended to be positively correlated with breast, colorectal, pancreatic, stomach and thyroid cancer. Alcoholic beverages were positively correlated to oesophageal cancer in men (r0 = 0·69, P < 0·001) and women (r–20 = 0·72, P < 0·001).
The present analysis provides initial insights into the impact of alcoholic beverages, and increasing use of animal over plant products, on the incidence of specific cancers in Africa. The findings support the need for epidemiological studies to investigate the role of diet in cancer development in Africa.
We propose the concept of the “Fish Revolution” to demarcate the dramatic increase in North Atlantic fisheries after AD 1500, which led to a 15-fold increase of cod (Gadus morhua) catch volumes and likely a tripling of fish protein to the European market. We consider three key questions: (1) What were the environmental parameters of the Fish Revolution? (2) What were the globalising effects of the Fish Revolution? (3) What were the consequences of the Fish Revolution for fishing communities? While these questions would have been considered unknowable a decade or two ago, methodological developments in marine environmental history and historical ecology have moved information about both supply and demand into the realm of the discernible. Although much research remains to be done, we conclude that this was a major event in the history of resource extraction from the sea, mediated by forces of climate change and globalisation, and is likely to provide a fruitful agenda for future multidisciplinary research.
An automated- electron microprobe system using an on-line 8,000 word minicomputer has been designed. The general principles and need for such a system is discussed. The microprobe-computer interface hardware consists of computer addressable axis positioners, scalers, timer and a digital to analog converter. The axis positioners are used to position the spectrometers and specimen stage, whereas the digital to analog converter is used to position the electron beam in a 1000 × 1000 point matrix. The digital to analog converter is also used to drive a X-Y recorder for computer plotting of calibration curves, pulse amplitude distributions, X-ray line profiles and wavelength scans. System software is written in the interactive CLASS language which was designed specifically for laboratory instrument control. The language permits large computer programs to be chained through a minicomputer while passing variables from one function to the next. The operating software consists of automatic peak location, sequencing of data collection, statistical analysis of data, and correction of data for fluorescence, absorption and atomic number effects. An automated quantitative analysis of several copper-gold alloys and a computerized test for specimen homogeneity is described to demonstrate system operation. Future automation considerations are also discussed.
Objectives: Long-term neurological response to treatment after a severe traumatic brain injury (sTBI) is a dynamic process. Failure to capture individual heterogeneity in recovery may impact findings from single endpoint sTBI randomized controlled trials (RCT). The present study re-examined the efficacy of erythropoietin (Epo) and transfusion thresholds through longitudinal modeling of sTBI recovery as measured by the Disability Rating Scale (DRS). This study complements the report of primary outcomes in the Epo sTBI RCT, which failed to detect significant effects of acute treatment at 6 months post-injury. Methods: We implemented mixed effects models to characterize the recovery time-course and to examine treatment efficacy as a function of time post-injury and injury severity. Results: The inter-quartile range (25th–75th percentile) of DRS scores was 20–28 at week1; 8–24 at week 4; and 3–17 at 6 months. TBI severity group was found to significantly interact with Epo randomization group on mean DRS recovery curves. No significant differences in DRS recovery were found in transfusion threshold groups. Conclusions: This study demonstrated the value of taking a comprehensive view of recovery from sTBI in the Epo RCT as a temporally dynamic process that is shaped by both treatment and injury severity, and highlights the importance of the timing of primary outcome measurement. Effects of Epo treatment varied as a function of injury severity and time. Future studies are warranted to understand the possible moderating influence of injury severity on treatment effects pertaining to sTBI recovery. (JINS, 2019, 25, 293–301)
Major depressive disorder (MDD) is a leading cause of disease burden worldwide, with lifetime prevalence in the United States of 17%. Here we present the results of the first prospective, large-scale, patient- and rater-blind, randomized controlled trial evaluating the clinical importance of achieving congruence between combinatorial pharmacogenomic (PGx) testing and medication selection for MDD.
1,167 outpatients diagnosed with MDD and an inadequate response to ≥1 psychotropic medications were enrolled and randomized 1:1 to a Treatment as Usual (TAU) arm or PGx-guided care arm. Combinatorial PGx testing categorized medications in three groups based on the level of gene-drug interactions: use as directed, use with caution, or use with increased caution and more frequent monitoring. Patient assessments were performed at weeks 0 (baseline), 4, 8, 12 and 24. Patients, site raters, and central raters were blinded in both arms until after week 8. In the guided-care arm, physicians had access to the combinatorial PGx test result to guide medication selection. Primary outcomes utilized the Hamilton Depression Rating Scale (HAM-D17) and included symptom improvement (percent change in HAM-D17 from baseline), response (50% decrease in HAM-D17 from baseline), and remission (HAM-D17<7) at the fully blinded week 8 time point. The durability of patient outcomes was assessed at week 24. Medications were considered congruent with PGx test results if they were in the ‘use as directed’ or ‘use with caution’ report categories while medications in the ‘use with increased caution and more frequent monitoring’ were considered incongruent. Patients who started on incongruent medications were analyzed separately according to whether they changed to congruent medications by week8.
At week 8, symptom improvement for individuals in the guided-care arm was not significantly different than TAU (27.2% versus 24.4%, p=0.11). However, individuals in the guided-care arm were more likely than those in TAU to achieve remission (15% versus 10%; p<0.01) and response (26% versus 20%; p=0.01). Remission rates, response rates, and symptom reductions continued to improve in the guided-treatment arm until the 24week time point. Congruent prescribing increased to 91% in the guided-care arm by week 8. Among patients who were taking one or more incongruent medication at baseline, those who changed to congruent medications by week 8 demonstrated significantly greater symptom improvement (p<0.01), response (p=0.04), and remission rates (p<0.01) compared to those who persisted on incongruent medications.
Combinatorial PGx testing improves short- and long-term response and remission rates for MDD compared to standard of care. In addition, prescribing congruency with PGx-guided medication recommendations is important for achieving symptom improvement, response, and remission for MDD patients.
Funding Acknowledgements: This study was supported by Assurex Health, Inc.
Animal models are valuable for the study of complex behaviours and physiology such as the control of appetite because genetic, pharmacological and surgical approaches allow the investigation of underlying mechanisms. However, the majority of such studies are carried out in just two species, laboratory mice and rats. These conventional laboratory species have been intensely selected for high growth rate and fecundity, and have a high metabolic rate and short lifespan. These aspects limit their translational relevance for human appetite control. This review will consider the value of studies carried out in a seasonal species, the Siberian hamster, which shows natural photoperiod-regulated annual cycles in appetite, growth and fattening. Such studies reveal that this long-term control is not simply an adjustment of the known hypothalamic neuronal systems that control hunger and satiety in the short term. Long-term cyclicity is probably driven by hypothalamic tanycytes, glial cells that line the ventricular walls of the hypothalamus. These unique cells sense nutrients and metabolic hormones, integrate seasonal signals and effect plasticity of surrounding neural circuits through their function as a stem cell niche in the adult. Studies of glial cell function in the hypothalamus offer new potential for identifying central targets for appetite and body weight control amenable to dietary or pharmacological manipulation.
Recent discussion and research has pointed to the changing functions of archdeacons within the Church of England as the role has become expanded to combine both the traditional statutory functions with flexible and visionary leadership skills within a changing church. This study draws on data collected in 2009 from 186 active and retired male archdeacons in order to assess the psychological profile established by that time. Compared with the psychological profile of 626 clergymen, male archdeacons were much more likely to prefer the SJ temperament (60 per cent compared with 31 per cent), a temperament ideally suited for effective administration of the statutory functions. As a consequence, preference for intuition was lower among male archdeacons (38 per cent compared with 62 per cent), as was preference for perceiving (9 per cent compared with 32 per cent), qualities core for flexibility and visionary leadership.
Patients suffering from an out-of-hospital cardiac arrest (OHCA) associated with an initial shockable rhythm have a better prognosis than their counterparts. The implications of recurrent or refractory malignant arrhythmia in such context remain unclear. The objective of this study is to evaluate the association between the number of prehospital shocks delivered and survival to hospital discharge among patients in OHCA.
This cohort study included adult patients with an initial shockable rhythm over a 5-year period from a registry of OHCA in Montreal, Canada. The relationship between the number of prehospital shocks delivered and survival to discharge was described using dynamic probabilities. The association between the number of prehospital shocks delivered and survival to discharge was assessed using multivariable logistic regression.
A total of 1,788 patients (78% male with a mean age of 64 years) were included in this analysis, of whom 536 (30%) received treatments from an advanced care paramedic. A third of the cohort (583 patients, 33%) survived to hospital discharge. The probability of survival was highest with the first shock (33% [95% confidence interval 30%-35%]), but decreased to 8% (95% confidence interval 4%-13%) following nine shocks. A higher number of prehospital shocks was independently associated with lower odds of survival (adjusted odds ratio=0.88 [95% confidence interval 0.85-0.92], p < 0.001).
Survival remains possible even after a high number of shocks for patients suffering from an OHCA with an initial shockable rhythm. However, requiring more shocks is independently associated with worse survival.
The importance of parasites as a selective force in host evolution is a topic of current interest. However, short-term ecological studies of host–parasite systems, on which such studies are usually based, provide only snap-shots of what may be dynamic systems. We report here on four surveys, carried out over a period of 12 years, of helminths of spiny mice (Acomys dimidiatus), the numerically dominant rodents inhabiting dry montane wadis in the Sinai Peninsula. With host age (age-dependent effects on prevalence and abundance were prominent) and sex (female bias in abundance in helminth diversity and in several taxa including Cestoda) taken into consideration, we focus on the relative importance of temporal and spatial effects on helminth infracommunities. We show that site of capture is the major determinant of prevalence and abundance of species (and higher taxa) contributing to helminth community structure, the only exceptions being Streptopharaus spp. and Dentostomella kuntzi. We provide evidence that most (notably the Spiruroidea, Protospirura muricola, Mastophorus muris and Gongylonema aegypti, but with exceptions among the Oxyuroidae, e.g. Syphacia minuta), show elements of temporal-site stability, with a rank order of measures among sites remaining similar over successive surveys. Hence, there are some elements of predictability in these systems.
High definition video from a towed camera system was used to describe the deep-sea benthic habitats within an elongate depression located at the western margin of Rockall Bank in the Hatton–Rockall Basin. At depths greater than 1190 m, an extensive area (10 km long by 1.5 km wide) of what appeared to be reduced sediments, bacterial mats and flocculent matter indicated possible cold-seep habitat. Plumes of sediment-rich fluid were observed alongside raised elongate features that gave topographic relief to the otherwise flat seafloor. In the deepest section of the depression (1215 m) dense flocculent matter was observed suspended in the water column, in places obscuring the seabed. Away from the bacterial mats, the habitat changed rapidly to sediments dominated by tube-dwelling polychaete worms and then to deep-sea sedimentary habitats more typical for the water depth (sponges and burrowing megafauna in areas of gentle slopes, and coral gardens on steeper slopes).
The solar magnesium II core-to-wing ratio has been a well-studied proxy for chromospheric activity since 1978. Daily measurements at high spectral (0.1 nm) resolution began with the launch of the Solar Radiation and Climate Experiment (SORCE) in 2003. The next generation of measurements from the Extreme Ultraviolet Sensor (EUVS) on the Geostationary Operational Environmental Satellite 16 (GOES-16) will add high time cadence (every 30 seconds) to the observational Mg II irradiance record. We present a comparison of the two measurements during the period of overlap.