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"Lewis, S J"
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The Brimstone Key
As the four friends known as the Grey Griffins begin school at Iron Bridge Academy, where children with special powers like theirs are trained to fight evil beings, rumors surface that a mad scientist known as the Clockwork King is back, and the Griffins must defeat his robotic war machines before total devastation is unleashed upon the world.
Book
Rotator cuff tendinopathy
Purpose:A review was conducted to synthesise the available research literature on the pathogenesis of rotator cuff tendinopathy.Relevance:Musculoskeletal disorders of the shoulder are extremely common, with reports of prevalence ranging from one in three people experiencing shoulder pain at some stage of their lives to approximately half the population experiencing at least one episode of shoulder pain annually. Pathology of the soft tissues of the shoulder, including the musculotendinous rotator cuff and subacromial bursa, is a principal cause of pain and suffering.Conclusions:The pathoaetiology of rotator cuff failure is multifactorial and results from a combination of intrinsic, extrinsic and environmental factors. The specialised morphology of the rotator cuff, together with the effects of stress shielding, may contribute to the development of rotator cuff tendinopathy. Profound changes within the subacromial bursa are strongly related to the pathology and resulting symptoms. A considerable body of research is necessary to more fully understand the aetiology and pathohistology of rotator cuff tendinopathy and its relationship with bursal pathology. Once this knowledge exists more effective management will become available.
Journal Article
The relic hunters
Tragedy divides the Grey Griffins, but their united quest to capture Von Strife continues, pitting them against killer clockworks, spider-like beasts, and an army of animated dead as they work together to prevent the building of The Paragon Engine.
Book
Current Concepts and Controversies in the Management of REM Sleep Behavior Disorder
Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by dream enactment and the loss of muscle atonia during REM sleep, known as REM sleep without atonia (RSWA). RBD can result in significant injuries, prompting patients to seek medical attention. However, in others, it may present only as non-violent behaviors noted as an incidental finding during polysomnography (PSG). RBD typically occurs in the context of synuclein-based neurodegenerative disorders but can also be seen accompanying brain lesions and be exacerbated by medications, particularly antidepressants. There is also an increasing appreciation regarding isolated or idiopathic RBD (iRBD). Symptomatic treatment of RBD is a priority to prevent injurious complications, with usual choices being melatonin or clonazepam. The discovery that iRBD represents a prodromal stage of incurable synucleinopathies has galvanized the research community into delineating the pathophysiology of RBD and defining biomarkers of neurodegeneration that will facilitate future disease-modifying trials in iRBD. Despite many advances, there has been no progress in available symptomatic or neuroprotective therapies for RBD, with recent negative trials highlighting several challenges that need to be addressed to prepare for definitive therapeutic trials for patients with this disorder. These challenges relate to i) the diagnostic and screening strategies applied to RBD, ii) the limited evidence base for symptomatic therapies, (iii) the existence of possible subtypes of RBD, (iv) the relevance of triggering medications, (v) the absence of objective markers of severity, (vi) the optimal design of disease-modifying trials, and vii) the implications around disclosing the risk of future neurodegeneration in otherwise healthy individuals. Here, we review the current concepts in the therapeutics of RBD as it relates to the above challenges and identify pertinent research questions to be addressed by future work.
Journal Article
Sleep disturbances in ADHD: investigating the contribution of polygenic liability for ADHD and sleep-related phenotypes
Sleep disturbances are common in attention deficit hyperactivity disorder (ADHD) and associated with poor outcomes. We tested whether, in children with ADHD, (1) polygenic liability for sleep phenotypes is over- or under-transmitted from parents, (2) this liability is linked to comorbid sleep disturbances, and (3) ADHD genetic risk is associated with comorbid sleep disturbances. We derived polygenic scores (PGS) for insomnia, chronotype, sleep duration, and ADHD, in 758 children (5–18 years old) diagnosed with ADHD and their parents. We conducted polygenic transmission disequilibrium tests for each sleep PGS in complete parent–offspring ADHD trios (
N
= 328) and an independent replication sample of ADHD trios (
N
= 844). Next, we tested whether insomnia, sleep duration, and ADHD PGS were associated with co-occurring sleep phenotypes (hypersomnia, insomnia, restless sleep, poor sleep quality, and nightmares) in children with ADHD. Children’s insomnia and chronotype PGS did not differ from mid-parent average PGS but long sleep duration PGS were significantly over-transmitted to children with ADHD. This was supported by a combined analysis using the replication sample. Insomnia, sleep duration, and ADHD PGS were not associated with comorbid sleep disturbances. There is weak evidence that children with ADHD over-inherit polygenic liability for longer sleep duration and do not differentially inherit polygenic liability for insomnia or chronotype. There was insufficient evidence that childhood sleep disturbances were driven by polygenic liability for ADHD or sleep traits, suggesting that sleep disturbances in ADHD may be aetiologically different to general population sleep phenotypes and do not index greater ADHD genetic risk burden.
Journal Article
double-blind placebo-controlled study of the effects of Lactobacillus acidophilus on plasma lipids
Objective: To select a probiotic bacteria that would reduce serum lipids in hypercholesterolaemic volunteers. Design: A strain of lactobacillus was selected for its ability to metabolise cholesterol under varying conditions in vitro. Freeze-dried Lactobacillus acidophilus or placebo were then given in a double-blind randomised crossover study to volunteers with high cholesterols. Subjects: A total of 80 volunteers with elevated cholesterols. Interventions: Volunteers were randomly allocated to receive either two capsules containing freeze-dried L. acidophilus 3 x 10(10) CFU or placebo three times a day for 6 weeks. After a 6-week washout period, volunteers were crossed over to another 6 weeks of capsules. Serum lipids were measured at the beginning and end of each interventional period. Results: L. acidophilus was able to reduce cholesterol and survive in an acid and bile environment. No changes in anthropomorphic measurements or in dietary records were seen between the baseline and final records or between the two sets of baseline records. There were no changes in serum lipids seen throughout the study. Conclusion: Despite the ability in vitro for L. acidophilus to reduce cholesterol, no effect was seen in volunteers.
Journal Article
Surgical and Radiology Trainees’ Proficiency in Reading Mammograms: the Importance of Education for Cancer Localisation
Medical imaging with mammography plays a very important role in screening and diagnosis of breast cancer, Australia’s most common female cancer. The visualisation of cancers on mammograms often forms a diagnosis and guidance for radiologists and breast surgeons, and education platforms that provide real cases in a simulated testing environment have been shown to improve observer performance for radiologists. This study reports on the performance of surgical and radiology trainees in locating breast cancers. An enriched test set of 20 mammography cases (6 cancer and 14 cancer free) was created, and 18 surgical trainees and 32 radiology trainees reviewed the cases via the Breast Screen Reader Assessment Strategy (BREAST) platform and marked any lesions identifiable. Further analysis of performance with high- and low-density cases was undertaken, and standard metrics including sensitivity and specificity. Radiology trainees performed significantly better than surgical trainees in terms of specificity (0.72 vs. 0.35; P < 0.01). No significant differences were observed between the surgical and radiology trainees in sensitivity or lesion sensitivity. Mixed results were obtained with participants regarding breast density, with higher density cases generally having lower performance. The higher specificity of the radiology trainees compared to the surgical trainees likely represents less exposure to negative mammography cases. The use of high-fidelity simulated self-test environments like BREAST is able to benchmark, understand and build strategies for improving cancer education in a safe environment, including identifying challenging scenarios like breast density for enhanced training.
Journal Article
Folic acid supplementation during pregnancy may protect against depression 21 months after pregnancy, an effect modified by MTHFR C677T genotype
Background/Objectives:
As low folate status has been implicated in depression, high folate intake, in the form of supplements, during pregnancy might offer protection against depression during pregnancy and postpartum.
Subjects/Methods:
We examined the association between change in self-reported depressive symptoms (Edinburgh Postnatal Depression Scale) at different timepoints during and following pregnancy and self-reported folic acid supplementation during pregnancy in a prospective cohort of 6809 pregnant women. We also tested whether there was a main effect of methylenetetrahydrofolate reductase (
MTHFR)
C677T genotype (which influences folate metabolism and intracellular levels of folate metabolites and homocysteine) on change in depression scores, and carried out our analysis of folic acid supplementation and depression stratifying by genotype.
Results:
We found no strong evidence that folic acid supplementation reduced the risk of depression during pregnancy and up to 8 months after pregnancy. However, we did find evidence to suggest that folic acid supplements during pregnancy protected against depression 21 months postpartum, and that this effect was more pronounced in those with the MTHFR C677T TT genotype (change in depression score from 8 months to 21 months postpartum among TT individuals was 0.66 (95% CI=0.31–1.01) among those not taking supplements, compared with −1.02 (95% CI=−2.22–0.18) among those taking supplements at 18 weeks pregnancy,
P
difference
=0.01).
Conclusions:
Low folate is unlikely to be an important risk factor for depression during pregnancy and for postpartum depression, but may be a risk factor for depression outside of pregnancy, especially among women with the MTHFR C677T TT genotype.
Journal Article
The thermolabile variant of MTHFR is associated with depression in the British Women's Heart and Health Study and a meta-analysis
Low dietary folate intake has been implicated as a risk factor for depression. However, observational epidemiological studies are plagued by problems of confounding, reverse causality and measurement error. A common polymorphism (C677T) in
MTHFR
is associated with methyltetrahydrofolate reductase (MTHFR) activity and circulating folate and homocysteine levels and offers insights into whether the association between low folate and depression is causal. We genotyped this polymorphism in 3478 women in the British Women's Heart and Health Study. In these women, we looked at the association between genotype and three indicators of depression; ever diagnosed as depressed, currently taking antidepressants and the EuroQol mood question. We also carried out a systematic review and meta-analysis of all published studies which have looked at the association between MTHFR C677T genotype and depression. In the British Women's Heart and Health Study, we found evidence of an increased risk of ever being diagnosed as depressed in MTHFR C677T TT individuals compared with CC individuals, odds ratio (OR) 1.35(95% CI: 1.01, 1.80). Furthermore, we identified eight other studies, which have examined the association between depression and MTHFR C677T. We were able to include all of these studies in our meta-analysis together with our results, obtaining an overall summary OR of 1.36 (95% CI: 1.11, 1.67,
P
=0.003). Since this genotype influences the functioning of the folate metabolic pathway, these findings suggest that folate or its derivatives may be causally related to risk of depression.
Journal Article
Rotator cuff tendinopathy/subacromial impingement syndrome: is it time for a new method of assessment?
Disorders of the shoulder are extremely common, with reports of prevalence ranging from 30% of people experiencing shoulder pain at some stage of their lives up to 50% of the population experiencing at least one episode of shoulder pain annually. In addition to the high incidence, shoulder dysfunction is often persistent and recurrent, with 54% of sufferers reporting ongoing symptoms after 3 years. To a large extent the substantial morbidity reflects (i) a current lack of understanding of the pathoaetiology, (ii) a lack of diagnostic accuracy in the assessment process, and (iii) inadequacies in current intervention techniques. Pathology of the rotator cuff and subacromial bursa is considered to be the principal cause of pain and symptoms arising from the shoulder. Generally these diagnostic labels relate more to a clinical hypothesis as to the underlying cause of the symptoms than to definitive evidence of the histological basis for the diagnosis or the correlation between structural failure and symptoms.Diagnosing rotator cuff tendinopathy or subacromial impingement syndrome currently involves performing a structured assessment that includes taking the patient’s history in conjunction with performing clinical assessment procedures that generally involve tests used to implicate an isolated structure. Based on the response to the clinical tests, a diagnosis of rotator cuff tendinopathy or subacromial impingement syndrome is achieved. The clinical diagnosis is strengthened with the findings from supporting investigations such as blood tests, radiographs, ultrasound, magnetic resonance imaging (MRI), computed axial tomography (CT), radionucleotide isotope scan, single photon emission computed tomography, electromyography, nerve conduction and diagnostic analgesic injection. This process eventually results in the formation of a clinical hypothesis, and then, in conjunction with the patient, a management plan is decided upon and implemented.This paper focuses on the dilemmas associated with the current process, and an alternative method for the clinical examination of the shoulder for this group of patients is proposed.
Journal Article