Using Cooperative Learning to Engage Students in Science

Cooperative learning can actively engage students in school science, stimulating curiosity and improving attitudes and motivation. Allen Thurston discusses the roles teachers and students can play to maximize its potential.

Drugs affecting the renin-angiotensin system and survival from cancer: a population based study of breast, colorectal and prostate cancer patient cohorts

Background: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are commonly prescribed to the growing number of cancer patients (more than two million in the UK alone) often to treat hypertension. However, increased fatal cancer in ARB users in a randomized trial and increased breast cancer recurrence rates in ACEI users in a recent observational study have raised concerns about their safety in cancer patients. We investigated whether ACEI or ARB use after breast, colorectal or prostate cancer diagnosis was associated with increased risk of cancer-specific mortality.

Methods: Population-based cohorts of 9,814 breast, 4,762 colorectal and 6,339 prostate cancer patients newly diagnosed from 1998 to 2006 were identified in the UK Clinical Practice Research Datalink and confirmed by cancer registry linkage. Cancer-specific and all-cause mortality were identified from Office of National Statistics mortality data in 2011 (allowing up to 13 years of follow-up). A nested case–control analysis was conducted to compare ACEI/ARB use (from general practitioner prescription records) in cancer patients dying from cancer with up to five controls (not dying from cancer). Conditional logistic regression estimated the risk of cancer-specific, and all-cause, death in ACEI/ARB users compared with non-users.

Results: The main analysis included 1,435 breast, 1,511 colorectal and 1,184 prostate cancer-specific deaths (and 7,106 breast, 7,291 colorectal and 5,849 prostate cancer controls). There was no increase in cancer-specific mortality in patients using ARBs after diagnosis of breast (adjusted odds ratio (OR) = 1.06 95% confidence interval (CI) 0.84, 1.35), colorectal (adjusted OR = 0.82 95% CI 0.64, 1.07) or prostate cancer (adjusted OR = 0.79 95% CI 0.61, 1.03). There was also no evidence of increases in cancer-specific mortality with ACEI use for breast (adjusted OR = 1.06 95% CI 0.89, 1.27), colorectal (adjusted OR = 0.78 95% CI 0.66, 0.92) or prostate cancer (adjusted OR = 0.78 95% CI 0.66, 0.92).

Conclusions: Overall, we found no evidence of increased risks of cancer-specific mortality in breast, colorectal or prostate cancer patients who used ACEI or ARBs after diagnosis. These results provide some reassurance that these medications are safe in patients diagnosed with these cancers.

Keywords: Colorectal cancer; Breast cancer; Prostate cancer; Mortality; Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers

Energy Efficiency through Significance-Based Computing

An extension of approximate computing, significance-based computing exploits applications' inherent error resiliency and offers a new structural paradigm that strategically relaxes full computational precision to provide significant energy savings with minimal performance degradation.

Next-generation sequencing-based molecular diagnosis of 82 retinitis pigmentosa probands from Northern Ireland

Retinitis pigmentosa (RP) is a group of inherited retinal disorders characterized by progressive photoreceptor degeneration. An accurate molecular diagnosis is essential for disease characterization and clinical prognoses. A retinal capture panel that enriches 186 known retinal disease genes, including 55 known RP genes, was developed. Targeted next-generation sequencing was performed for a cohort of 82 unrelated RP cases from Northern Ireland, including 46 simplex cases and 36 familial cases. Disease-causing mutations were identified in 49 probands, including 28 simplex cases and 21 familial cases, achieving a solving rate of 60 %. In total, 65 pathogenic mutations were found, and 29 of these were novel. Interestingly, the molecular information of 12 probands was neither consistent with their initial inheritance pattern nor clinical diagnosis. Further clinical reassessment resulted in a refinement of the clinical diagnosis in 11 patients. This is the first study to apply next-generation sequencing-based, comprehensive molecular diagnoses to a large number of RP probands from Northern Ireland. Our study shows that molecular information can aid clinical diagnosis, potentially changing treatment options, current family counseling and management.

Summary of the Snowmastodon Project Special Volume: A high-elevation, multi-proxy biotic and environmental record of MIS 6-4 from the Ziegler Reservoir fossil site, Snowmass Village, Colorado, USA

In North America, terrestrial records of biodiversity and climate change that span Marine Oxygen Isotope Stage (MIS) 5 are rare. Where found, they provide insight into how the coupling of the ocean-atmosphere system is manifested in biotic and environmental records and how the biosphere responds to climate change. In 2010-2011, construction at Ziegler Reservoir near Snowmass Village, Colorado (USA) revealed a nearly continuous, lacustrine/wetland sedimentary sequence that preserved evidence of past plant communities between similar to 140 and 55 lea, including all of MIS 5. At an elevation of 2705 m, the Ziegler Reservoir fossil site also contained thousands of well-preserved bones of late Pleistocene megafauna, including mastodons, mammoths, ground sloths, horses, camels, deer, bison, black bear, coyotes, and bighorn sheep. In addition, the site contained more than 26,000 bones from at least 30 species of small animals including salamanders, otters, muskrats, minks, rabbits, beavers, frogs, lizards, snakes, fish, and birds. The combination of macro- and micro-vertebrates, invertebrates, terrestrial and aquatic plant macrofossils, a detailed pollen record, and a robust, directly dated stratigraphic framework shows that high-elevation ecosystems in the Rocky Mountains of Colorado are climatically sensitive and varied dramatically throughout MIS 5 

Impact of smoking and smoking cessation on cardiovascular events and mortality among older adults: meta-analysis of individual participant data from prospective cohort studies of the CHANCES consortium

OBJECTIVE: To investigate the impact of smoking and smoking cessation on cardiovascular mortality, acute coronary events, and stroke events in people aged 60 and older, and to calculate and report risk advancement periods for cardiovascular mortality in addition to traditional epidemiological relative risk measures.

DESIGN: Individual participant meta-analysis using data from 25 cohorts participating in the CHANCES consortium. Data were harmonised, analysed separately employing Cox proportional hazard regression models, and combined by meta-analysis.

RESULTS: Overall, 503,905 participants aged 60 and older were included in this study, of whom 37,952 died from cardiovascular disease. Random effects meta-analysis of the association of smoking status with cardiovascular mortality yielded a summary hazard ratio of 2.07 (95% CI 1.82 to 2.36) for current smokers and 1.37 (1.25 to 1.49) for former smokers compared with never smokers. Corresponding summary estimates for risk advancement periods were 5.50 years (4.25 to 6.75) for current smokers and 2.16 years (1.38 to 2.39) for former smokers. The excess risk in smokers increased with cigarette consumption in a dose-response manner, and decreased continuously with time since smoking cessation in former smokers. Relative risk estimates for acute coronary events and for stroke events were somewhat lower than for cardiovascular mortality, but patterns were similar.

CONCLUSIONS: Our study corroborates and expands evidence from previous studies in showing that smoking is a strong independent risk factor of cardiovascular events and mortality even at older age, advancing cardiovascular mortality by more than five years, and demonstrating that smoking cessation in these age groups is still beneficial in reducing the excess risk.

Musculoskeletal (MSK) and Sport and Exercise Medicine (SEM) in General Practice (GP): A Novel GP-based clinic

The problem-Musculoskeletal (MSK) symptoms are common within primary care but some GPs are not comfortable managing these; waiting times for hospital appointments are a major cause of patients’ complaints. Current UK healthcare policies emphasise a need for more community-based management. We aimed to pilot an innovative general practice-based clinic to improve the management of MSK and Sport and Exercise Medicine (SEM) symptoms within general practice.

The approach-This project was conducted in an inner-city practice of approximately 9,000 patients and 5 GP partners. The practice commissioned a novel monthly 4-hour clinic staffed by one GP with a specialist interest in MSK and SEM conditions. Each patient was allocated a 20-minute appointment. All primary care staff within the practice could refer any patient for whom they considered hospital referral appropriate, with no specific exclusion criteria. Management plans included injection therapy, exercise prescription and onward referral. After three months (August-October 2014) numbers of consultations, sources of referral, reasons for referral and management outcomes were described; patient satisfaction was assessed by questionnaire, offered to 10 randomly selected patients by reception staff and self-completed by patients. Costs of the clinic were compared to current options.

Findings- All patients (14 males; 21 females; aged 35-77 years), were seen within four weeks of referral (one third of orthopaedic referrals in 2013 waited over 9 weeks for appointment). Most were referred from other GPs; some came from physiotherapy and podiatry. Shoulder problems were the most frequent reason for referral. The commonest management option was steroid injection, with most patients being given advice regarding exercise and analgesia; there were 3 onward referrals (2 physiotherapy; 1 rheumatology).

Comparing August-October data in 2014 and 2013, total, orthopaedic and rheumatology referrals were reduced by 147, 2 and 3, respectively; within the practice MSK presentations and physiotherapy and x-ray referrals were 60, 47 and 90 fewer, respectively.

The cost per attendance at the clinic was £61; initial orthopaedic-ICAT assessments cost £82 and a consultant appointment £213.

Satisfaction questionnaires were returned by all 10 selected participants and provided positive feedback, expressing preference for community-based, rather than hospital, management.

Consequence- Our pilot study indicates that this novel service model has potential for efficient and effective management of MSK and SEM complaints in primary care, reducing the need for hospital referral and the clinical burden on general practices. The innovation deserves further evaluation in a full-scale trial to determine its generalisability to other practice settings and populations.

Determinants of breastfeeding initiation in Ireland

BACKGROUND: Ireland continues to rank among countries with the lowest breastfeeding initiation rates. National and regional studies also show that few women in Ireland who initiate exclusive breastfeeding continue to breastfeed for the recommended 6 months.

AIM: To assess the rate of exclusive and partial breastfeeding in Ireland at three time periods: birth to 48 h, 3-4 months following birth, and when the infant was 6-7 months old.

METHODS: A longitudinal national cohort survey of 2527 mothers.

RESULTS: Findings show that just 56 % (n = 1002) of mothers initiated breastfeeding at birth and, at 48 h, 42 % (n = 1064) of women were exclusively breastfeeding their babies. At 6-7 months, only 2.4 % of the 2527 mothers who took part, reported exclusive breastfeeding. Irish women were less likely to initiate breastfeeding (52.6 %) compared with Polish (82.2 %), British (64.5 %), and other nationalities (74.6 %). Multivariate analysis also revealed significant relationships between initiation and socio-economic variables, with mothers' health insurance status being of particular importance.

CONCLUSION: The results highlight the necessity to support the initiation and maintenance of breastfeeding in Ireland, in order to reduce rates of infant morbidity.

Arteriovenous fistula outcomes in the elderly

OBJECTIVE: Over several decades, there has been an increase in the number of elderly patients requiring hemodialysis. These older patients typically have an increased incidence of comorbidities including diabetes, hypertension, and peripheral vascular disease. We undertook a systematic review of the current literature to assess outcomes of arteriovenous fistula (AVF) formation in the elderly and to compare the results of radiocephalic AVFs vs brachiocephalic AVFs in older patients.

METHODS: A literature search was performed using MEDLINE, Embase, PubMed, and the Cochrane Library. All retrieved articles published before December 31, 2014 (and in English) primarily describing the creation of hemodialysis vascular access for elderly patients were considered for inclusion. We report pooled AVF patency rates and a comparison of radiocephalic vs brachiocephalic AVF patency rates using odds ratios (ORs).

RESULTS: Of 199 relevant articles reviewed, 15 were deemed eligible for the review. The pooled 12-month primary and secondary AVF patency rates were 53.6% (95% confidence interval [CI], 47.3-59.9) and 71.6% (95% CI, 59.2-82.7), respectively. Comparison of radiocephalic vs brachiocephalic AVF patency rates demonstrated that radiocephalic AVFs have inferior primary (OR, 0.72; 95% CI, 0.55-0.93; P = .01) and secondary (OR, 0.76; 95% CI, 0.58-1.00; P = .05) patency rates.

CONCLUSIONS: This meta-analysis confirms that adequate 12-month primary and secondary AVF patency rates can be achieved in elderly patients. Brachiocephalic AVFs have both superior primary and secondary patency rates at 12 months compared with radiocephalic AVFs. These important data can inform clinicians' and patients' decision-making about suitability of attempting AVF formation in older persons.

Survival of patients with skin melanoma in Europe increases further: Results of the EUROCARE-5 study

Background In Europe skin melanoma (SM) survival has increased over time. The aims were to evaluate recent trends and differences between countries and regions of Europe.

Methods Relative survival (RS) estimates and geographical comparisons were based on 241,485 patients aged 15 years and over with a diagnosis of invasive SM in Europe (2000-2007). Survival time trends during 1999-2007 were estimated using the period approach, for 213,101 patients. Age, gender, sub-sites and morphology subgroups were considered. 

Results In European patients, estimated 5-year RS was 83% (95% confidence interval, CI 83-84%). The highest values were found for patients resident in Northern (88%; 87-88%) and Central (88%; 87-88%) Europe, followed by Ireland and United Kingdom (UK) (86%; 85-86%) and Southern Europe (83%; 82-83%). The lowest survival was in Eastern Europe (74%; 74-75%). Within regions the intercountry absolute difference in percentage points of RS varied from 4% (North) to 34% (East). RS decreased markedly with patients' age and was higher in women than men. Differences according to SM morphology and skin sub-sites also emerged. Survival has slightly increased from 1999 to 2007, with a small improvement in Northern and the most pronounced improvement in Eastern Europe. 

Discussion SM survival is high and still increasing in European patients. The gap between Northern and Southern and especially Eastern European countries, although still present, diminished over time. Differences in stage distribution at diagnosis may explain most of the geographical differences. However, part of the improvement in survival may be attributed to overdiagnosis from early diagnosis practices.

Human-directed gazing behaviour in puppies and adult dogs, Canis lupus familiaris

Recent evidence indicates that dogs' sociocognitive abilities and behaviour in a test situation are shaped by both genetic factors and life experiences. We used the 'unsolvable task' paradigm to investigate the effect of breed and age/experience on the use of human-directed gazing behaviour. Following a genetic classification based on recent genome analyses, dogs were allocated to three breed groups, namely Primitive, Hunting/Herding and Molossoid. Furthermore, we tested dogs at 2 months, 4.5. months and as adults. The test consisted of three solvable trials in which dogs could obtain food by manipulating a plastic container followed by an unsolvable trial in which obtaining the food became impossible. The dogs' behaviour towards the apparatus and the people present was analysed. At 2 months no breed group differences emerged and although human-directed gazing behaviour was observed in approximately half of the pups, it occurred for brief periods, suggesting that the aptitude to use human-directed gazing as a request for obtaining help probably develops at a later date when dogs have had more experience with human communication. Breed group differences, however, did emerge strongly in adult dogs and, although less pronounced, also in 4.5-month-old subjects, with dogs in the Hunting/Herding group showing significantly more human-directed gazing behaviour than dogs in the other two breed groups. These results suggest that, although the domestication process may have shaped the dog's human-directed communicative abilities, the later selection for specific types of work might also have had a significant impact on their emergence. © 2011 The Association for the Study of Animal Behaviour.

Visual outcomes of cataract surgery performed by supervised novice surgeons during training in rural China

To assess the outcomes of cataract surgery performed by novice surgeons during training in a rural programme. Design: Retrospective study. Participants: Three hundred thirty-four patients operated by two trainees under supervision at rural Chinese county hospitals. Methods: Two trainees performed surgeries under supervision. Visual acuity, refraction and examinations were carried out 3 months postoperatively. Main Outcome Measures: Postoperative uncorrected visual acuity, pinhole visual acuity, causes of visual impairment (postoperative uncorrected visual acuity<6/18) Results: Among 518 operated patients, 426 (82.2%) could be contacted and 334 (64.4% of operated patients) completed the examinations. The mean age was 74.1±8.8 years and 62.9% were women. Postoperative uncorrected visual acuity was available in 372 eyes. Among them, uncorrected visual acuity was ≥6/18 in 278 eyes (74.7%) and <6/60 in 60 eyes (16.1%), and 323 eyes (86.8%) had pinhole visual acuity≥6/18 and 38 eyes (10.2%) had pinhole visual acuity<6/60. Main causes of visual impairment were uncorrected refractive error (63.9%) and comorbid eye disease (24.5%). Comorbid eye diseases associated with pinhole visual acuity<6/60 (n=23, 6.2%) included glaucoma, other optic nerve atrophy, vitreous haemorrhage and retinal detachment. Conclusions: The findings suggest that hands-on training remains safe and effective even when not implemented in centralized training centres. Further refinement of the training protocol, providing postoperative refractive services and more accurate preoperative intraocular lens calculations, can help optimize outcomes. © 2012 The Authors Clinical and Experimental Ophthalmology © 2012 Royal Australian and New Zealand College of Ophthalmologists.