Temporal trends in mode, site and stage of presentation with the introduction of colorectal cancer screening: a decade of experience from the West of Scotland

background:  Population colorectal cancer screening programmes have been introduced to reduce cancer-specific mortality through the detection of early-stage disease. The present study aimed to examine the impact of screening introduction in the West of Scotland. methods:  Data on all patients with a diagnosis of colorectal cancer between January 2003 and December 2012 were extracted from a prospectively maintained regional audit database. Changes in mode, site and stage of presentation before, during and after screening introduction were examined. results:  In a population of 2.4 million, over a 10-year period, 14 487 incident cases of colorectal cancer were noted. Of these, 7827 (54%) were males and 7727 (53%) were socioeconomically deprived. In the postscreening era, 18% were diagnosed via the screening programme. There was a reduction in both emergency presentation (20% prescreening vs 13% postscreening, P0.001) and the proportion of rectal cancers (34% prescreening vs 31% pos-screening, P0.001) over the timeframe. Within non-metastatic disease, an increase in the proportion of stage I tumours at diagnosis was noted (17% prescreening vs 28% postscreening, P0.001). conclusions:  Within non-metastatic disease, a shift towards earlier stage at diagnosis has accompanied the introduction of a national screening programme. Such a change should lead to improved outcomes in patients with colorectal cancer

Comparative population structure of <i>Plasmodium malariae</i> and <i>Plasmodium falciparum</i> under different transmission settings in Malawi

&lt;b&gt;Background:&lt;/b&gt; Described here is the first population genetic study of Plasmodium malariae, the causative agent of quartan malaria. Although not as deadly as Plasmodium falciparum, P. malariae is more common than previously thought, and is frequently in sympatry and co-infection with P. falciparum, making its study increasingly important. This study compares the population parameters of the two species in two districts of Malawi with different malaria transmission patterns - one seasonal, one perennial - to explore the effects of transmission on population structures. &lt;BR/&gt; &lt;b&gt;Methods:&lt;/b&gt; Six species-specific microsatellite markers were used to analyse 257 P. malariae samples and 257 P. falciparum samples matched for age, gender and village of residence. Allele sizes were scored to within 2 bp for each locus and haplotypes were constructed from dominant alleles in multiple infections. Analysis of multiplicity of infection (MOI), population differentiation, clustering of haplotypes and linkage disequilibrium was performed for both species. Regression analyses were used to determine association of MOI measurements with clinical malaria parameters. &lt;BR/&gt; &lt;b&gt;Results:&lt;/b&gt; Multiple-genotype infections within each species were common in both districts, accounting for 86.0% of P. falciparum and 73.2% of P. malariae infections and did not differ significantly with transmission setting. Mean MOI of P. falciparum was increased under perennial transmission compared with seasonal (3.14 vs 2.59, p = 0.008) and was greater in children compared with adults. In contrast, P. malariae mean MOI was similar between transmission settings (2.12 vs 2.11) and there was no difference between children and adults. Population differentiation showed no significant differences between villages or districts for either species. There was no evidence of geographical clustering of haplotypes. Linkage disequilibrium amongst loci was found only for P. falciparum samples from the seasonal transmission setting. &lt;BR/&gt; &lt;b&gt;Conclusions:&lt;/b&gt; The extent of similarity between P. falciparum and P. malariae population structure described by the high level of multiple infection, the lack of significant population differentiation or haplotype clustering and lack of linkage disequilibrium is surprising given the differences in the biological features of these species that suggest a reduced potential for out-crossing and transmission in P. malariae. The absence of a rise in P. malariae MOI with increased transmission or a reduction in MOI with age could be explained by differences in the duration of infection or degree of immunity compared to P. falciparum

Stereoselective handling of perhexiline:Implications regarding accumulation within the human myocardium

Purpose: Perhexiline is a prophylactic anti-ischaemic agent with weak calcium antagonist effect which has been increasingly utilised in the management of refractory angina. The metabolic clearance of perhexiline is modulated by CYP2D6 metaboliser status and stereoselectivity. The current study sought to (1) determine whether the acute accumulation of perhexiline in the myocardium is stereoselective and (2) investigate the relationship between duration of short-term therapy and the potential stereoselective effects of perhexiline within myocardium. Method: Patients (n = 129) from the active arm of a randomised controlled trial of preoperative perhexiline in cardiac surgery were treated with oral perhexiline for a median of 9 days. Correlates of atrial and ventricular concentrations of enantiomers were sought via univariate followed by multivariate analyses. Results: Myocardial uptake of both (+) and (−) perhexiline was greater in ventricles than in atria, and there was more rapid clearance of (−) than (+) perhexiline. The main determinants of atrial uptake of both (+) and (−) perhexiline were the plasma concentrations [(+) perhexiline: β = −0.256, p = 0.015; (−) perhexiline: β = −0.347, p = 0.001] and patients’ age [(+) perhexiline: β = 0.300, p = 0.004; (−) perhexiline: β = 0.288, p = 0.005]. Atrial uptake of (+) enantiomer also varied directly with duration of therapy (β = 0.228, p = 0.025), while atrial uptake of (−) perhexiline varied inversely with simultaneous heart rate (β = −0.240, p = 0.015). Conclusion: (1) Uptake of both perhexiline enantiomers into atrium is greater with advanced age and displays evidence of both saturability and minor stereoselectivity. (2) Atrial uptake of (−) perhexiline may selectively modulate heart rate reduction

Pre-pregnancy body mass index and gestational weight gain and their effects on pregnancy and birth outcomes: a cohort study in West Sumatra, Indonesia

Background: Indonesia has a considerably high incidence of maternal and infant mortality. The country has however been experiencing a social and economic transition, influencing its general population demographics and nutritional status including the state of health and nutrition of pregnant women. This study aimed to explore body mass index (BMI) and gestational weight gain (GWG), and their relationship with pregnancy outcomes in a sample of Indonesian pregnant women. Methods: This observational cohort study included a total of 607 pregnant women who were recruited in 2010 from maternity clinics in Western Sumatra, Indonesia. Multiple logistic and regression analyses were undertaken to compare pregnancy and birth outcomes for different BMI and GWG, using normal weight women and women with a recommended weight gain as the referent groups. Results: The prevalence of underweight (BMI < 18.5 kg/m2) in pregnancy was high at 20.1%; while 21.7% of women were overweight (BMI: 23.0–27.4 kg/m2) and 5.3% obese (BMI ≥ 27.5 kg/m2) using the Asian BMI classifications. The incidence of overweight (BMI: 25.0–29.9 kg/m2) and obese (BMI ≥ 30.0 kg/m2) according to the international BMI classifications were 13.5% and 1.1% respectively. The majority of women gained inadequate weight in pregnancy compared to the Institute of Medicine (IOM)recommendations, especially those who had a normal BMI. Birthweight adjusted mean difference aMD (95% confidence interval) 205 (46,365) and the odds of macrosomia adjusted odds ratio aOR 13.46 (2.32–77.99) significantly increased in obese women compared to those with a normal BMI. Birthweight aMD -139 (−215, −64) significantly decreased in women with inadequate GWG compared to those with recommended GWG, while SGA aOR 5.44 (1.36, 21.77) and prematurity aOR 3.55 (1.23, 10.21) increased. Conclusions: Low nutritional status and inadequate GWG remain a cause for concern in these women. The higher odds of macrosomia with increasing maternal BMI and higher odds of prematurity and small for gestational age infants with inadequate weight gain also require attention. Research and practice recommendations: Urgent attention is required by researchers, policy makers and decision makers to facilitate development of culturally sensitive interventions to enhance nutritional status and health of mothers and babies, in an area known for its high incidence of maternal and neonatal mortality. Keywords: Maternal BMI, Gestational weight gain, Pregnancy outcomes, Birthweight, Indonesia, Cohort stud

Perceived stressors of climate vulnerability across scales in the Savannah zone of Ghana: a participatory approach

Smallholder farmers in sub-Saharan Africa are confronted with climatic and non-climatic stressors. Research attention has focused on climatic stressors, such as rainfall variability, with few empirical studies exploring non-climatic stressors and how these interact with climatic stressors at multiple scales to affect food security and livelihoods. This focus on climatic factors restricts understanding of the combinations of stressors that exacerbate the vulnerability of farming households and hampers the development of holistic climate change adaptation policies. This study addresses this particular research gap by adopting a multi-scale approach to understand how climatic and non-climatic stressors vary, and interact, across three spatial scales (household, community and district levels) to influence livelihood vulnerability of smallholder farming households in the Savannah zone of northern Ghana. This study across three case study villages utilises a series of participatory tools including semi-structured interviews, key informant interviews and focus group discussions. The incidence, importance, severity and overall risk indices for stressors are calculated at the household, community, and district levels. Results show that climatic and non-climatic stressors were perceived differently; yet, there were a number of common stressors including lack of money, high cost of farm inputs, erratic rainfall, cattle destruction of crops, limited access to markets and lack of agricultural equipment that crossed all scales. Results indicate that the gender of respondents influenced the perception and severity assessment of stressors on rural livelihoods at the community level. Findings suggest a mismatch between local and district level priorities that have implications for policy and development of agricultural and related livelihoods in rural communities. Ghana’s climate change adaptation policies need to take a more holistic approach that integrates both climatic and non-climatic factors to ensure policy coherence between national climate adaptation plans and District development plans

Effect of Information and Telephone-Guided Access to Community Support for People with Chronic Kidney Disease: Randomised Controlled Trial

Background: Implementation of self-management support in traditional primary care settings has proved difficult, encouraging the development of alternative models which actively link to community resources. Chronic kidney disease (CKD) is a common condition usually diagnosed in the presence of other co-morbidities. This trial aimed to determine the effectiveness of an intervention to provide information and telephone-guided access to community support versus usual care for patients with stage 3 CKD. Methods and Findings: In a pragmatic, two-arm, patient level randomised controlled trial 436 patients with a diagnosis of stage 3 CKD were recruited from 24 general practices in Greater Manchester. Patients were randomised to intervention (215) or usual care (221). Primary outcome measures were health related quality of life (EQ-5D health questionnaire), blood pressure control, and positive and active engagement in life (heiQ) at 6 months. At 6 months, mean health related quality of life was significantly higher for the intervention group (adjusted mean difference = 0.05; 95% CI = 0.01, 0.08) and blood pressure was controlled for a significantly greater proportion of patients in the intervention group (adjusted odds ratio = 1.85; 95% CI = 1.25, 2.72). Patients did not differ significantly in positive and active engagement in life. The intervention group reported a reduction in costs compared with control. Conclusions: An intervention to provide tailored information and telephone-guided access to community resources was associated with modest but significant improvements in health related quality of life and better maintenance of blood pressure control for patients with stage 3 CKD compared with usual care. However, further research is required to identify the mechanisms of action of the intervention

Learning environment associated with use of mixed mode delivery model among secondary business studies students in Singapore

At many teacher education institutes around the world, preservice teachers are empowered to use pedagogical tools and strategies that engage their students. We used a modified version of the Constructivist Learning Environment Survey (CLES) to evaluate the effectiveness of a pedagogical model known as the Mixed Mode Delivery (MMD) model in terms of the CLES’s five scales of personal relevance, uncertainty, critical voice, shared control and negotiation. Comparisons were made between 2,216 secondary school students taught by the preservice teachers in an MMD group and 991 students in a control group in terms of the relative magnitudes of the gap between the actual and preferred learning environment in students’ school classrooms. The findings supported the positive impact of using MMD in terms of students’ perceptions of their classroom environments for all CLES scales

Does dapagliflozin regress left ventricular hypertrophy in patients with type 2 diabetes?:A prospective, double-blind, randomised, placebo-controlled study

Background: Patients with diabetes have a two to fourfold increased risk for development of and death from cardiovascular disease [CVD]. The current oral hypoglycaemic agents result in limited reduction in this cardiovascular risk. Sodium glucose linked co-transporter type 2 [SGLT2] inhibitors are a relatively new class of antidiabetic agent that have been shown to have potential cardiovascular benefits. In support of this, the EMPA-REG trial showed a striking 38% and 35% reduction in cardiovascular mortality and heart failure [HF] hospitalisation respectively. The exact mechanism (s) responsible for these effects remain (s) unclear. One potential mechanism is regression of Left ventricular hypertrophy (LVH).Methods: The DAPA-LVH trial is a prospective, double-blind, randomised, placebo-controlled 'proof of concept' single-centre study that has been ongoing since January 2017. It is designed specifically to assess whether the SGLT2 inhibitor dapagliflozin regresses left ventricular [LV] mass in patients with diabetes and left ventricular hypertrophy [LVH]. We are utilising cardiac and abdominal magnetic resonance imaging [MRI] and ambulatory blood pressure monitoring to quantify the cardiovascular and systemic effects of dapagliflozin 10 mg once daily against standard care over a 1 year observation period. The primary endpoint is to detect the changes in LV mass. The secondary outcomes are to assess the changes in, LV volumes, blood pressure, weight, visceral and subcutaneous fat.Discussion: This trial will be able to determine if SGLT2 inhibitor therapy reduces LV mass in patient with diabetes and LVH thereby strengthening their position as oral hypoglycaemic agents with cardioprotective benefits.Trial Registration: Clinical Trials.gov: NCT02956811 . Registered November 2016.</p

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta