Reef islands have continually adjusted to environmental change over the past two millennia.

Global environmental change is identified as a driver of physical transformation of coral reef islands over the past half-century, and next 100 years, posing major adaptation challenges to island nations. Here we resolve whether these recent documented changes in islands are unprecedented compared with the pre-industrial era. We utilise radiometric dating, geological, and remote sensing techniques to document the dynamics of a Maldivian reef island at millennial to decadal timescales. Results show the magnitude of island change over the past half-century (±40 m movement) is not unprecedented compared with paleo-dynamic evidence that reveals large-scale changes in island dimension, shape, beach levels, as well as positional changes of ±200 m since island formation ~1,500 years ago. Results highlight the value of a multi-temporal methodological approach to gain a deeper understanding of the dynamic trajectories of reef islands, to support development of adaptation strategies at timeframes relevant to human security.

The junior doctor changeover effect: does it exist in general surgery?

INTRODUCTION: Junior doctor changeover has been perceived as a period of increased risk to patients. However, there is a paucity of contemporary evidence of this 'changeover effect'. The aim of this study was to evaluate the presence of an adverse patient effect during periods of junior doctor changeover. METHODS: Data were requested on all patients aged 18 years or older admitted acutely under General Surgery in the North of England between 2005 and 2016. This included patient characteristics, diagnoses, comorbidities, procedure codes, mortality and length of stay. Patients were included in the study if they were admitted during the 'changeover week'; defined as the first day of the changeover followed by the six subsequent days. For junior trainees (FY1-CT2), this is the first Wednesday of August, December and April each year. For higher surgical trainees (ST3-ST8), it is the first Wednesday in October. Another week, four weeks prior, was chosen as a historical comparator. RESULTS: In total, 61,714 patients were included in this study. Patient characteristics did not vary between the cohorts. There was no difference in 30-day mortality between changeover and non-changeover groups (2.5% vs 2.6%, p = 0.280) or length of stay (5.3 vs 5.2, p = 0.613). Changeover week was not a predictor of increased mortality (OR 1.06, p = 0.302) following multivariable adjustment. Further analysis of the first junior and higher specialty trainee periods, August and October, respectively, showed no significant difference for measured outcomes. CONCLUSIONS: This retrospective cohort study provides contemporary evidence that the 'changeover effect' does not exist in acute general surgical admissions in the UK.

Does amantadine maintain function in long-established brain injury? A single case experimental design.

OBJECTIVE: The role of dopamine agonist (DA) in restoring consciousness and cognition in recovery phase following acquired brain injury (ABI) is established (1-5). The role in later recovery is less well defined. We report a single case experimental design (SCED) trial of amantadine demonstrating improvement in function, six years following ABI. METHOD: A scoring system based on established abilities in personal care and interaction was used to identify tasks with component actions, 34 actions in total, each ranked in terms of quality of response to a request or prompt. Actions were scored on maintenance dose amantadine; on withdrawal; and after reintroduction. Daytime sleep duration was also recorded. RESULTS: At 3rd and 5th weeks post withdrawal, deterioration was noted in 27 of 34 graded activities. At 3rd and 5th weeks following reintroduction, all but 3 grades returned to baseline or better. Afternoon sleep duration increased from 35 to 80 minutes during withdrawal period returning towards baseline on amantadine resumption. CONCLUSION: We believe this provides evidence for benefit of amantadine in sustaining function following ABI. The SCED model used provides a template for others to use to identify comparable change in similar trials.

Patient Outcomes Following Emergency Bowel Resection for Inflammatory Bowel Disease and the Impact of Surgical Subspecialisation in the North of England: A Retrospective Cohort Study.

BACKGROUND: Management of inflammatory bowel disease (IBD) has changed considerably over recent years, which has coincided with increased subspecialisation amongst general surgeons. This study evaluated the demographics and outcomes of patients with IBD undergoing bowel resection and assessed for the potential impact of surgical subspecialisation. METHODS: Patient demographic, operative and outcome data were collected for patients undergoing a bowel resection secondary to IBD, admitted acutely to NHS trusts in the North of England between 2002 and 2016. The primary outcome of interest was 30-day post-operative mortality, with secondary outcomes: length of stay, stoma and anastomosis rates. RESULTS: A total of 913 patients were included in the study cohort. A reduction in the number of resections was noted over time (2002-2006: 361 vs. 2012-2016: 262). No change was observed for 30-day mortality over the study period (3.9%, p = 0.233). Length of stay was also unchanged (p = 0.949). Laparoscopic surgery was increasingly utilised (0.6% vs. 17.2%, p < 0.001) in recent years, and by colorectal subspecialists (p = 0.003). More patients were managed by a colorectal consultant latterly (2002-2006: 45.4% vs. 2012-2016: 63.7%, p < 0.001). There was no difference between colorectal and other subspecialists in mortality (p = 0.156), length of stay (p = 0.201), stoma (p = 0.629) or anastomosis (p = 0.659) rates, including following multivariable adjustment. CONCLUSION: The study demonstrated a significant reduction in the number of resections over time, increased utilisation of a laparoscopic approach and a shift towards the care of IBD surgical patients being by a colorectal subspecialist. However, these changes do not correspond with improved surgical outcomes.

Nonpharmacologic and pharmacologic management of acute pain from non­low back, musculoskeletal injuries in adults: a clinical guideline from the American College of Physicians and American Academy of Family Physicians

The American College of Physicians (ACP) and American Academy of Family Physicians (AAFP) developed this guideline to provide clinical recommendations on nonpharmacologic and pharmacologic management of acute pain from non­low back, musculoskeletal injuries in adults in the outpatient setting. The guidance is based on current best available evidence about benefits and harms, taken in the context of costs and patient values and preferences. This guideline does not address noninvasive treatment of low back pain, which is covered by a separate ACP guideline that has also been endorsed by AAFP.

The National Psoriasis Foundation psoriasis treatment targets in real-world patients: prevalence and association with patient-reported outcomes in the Corrona Psoriasis Registry.

INTRODUCTION: The National Psoriasis Foundation (NPF) published treat-to-target guidelines for psoriasis, yet their applicability in clinical practice remains unknown. OBJECTIVES: To estimate the proportion of psoriasis patients meeting the NPF's body surface area (BSA) 'target' (≤1%) and 'acceptable' (≤3%) response criteria and the cross-sectional associations of these criteria with patient-reported outcomes (PROs) in the Corrona Psoriasis Registry. METHODS: Separately for three independent cross-sectional cohorts of patients at the (i) enrolment, (ii) 6-month and (iii) 12-month visits, we calculated the proportion of patients with BSA ≤1% and ≤3%. Furthermore, we calculated odds ratios estimating the risk of PROs associated with not meeting criteria in the 6-month cohort. RESULTS: The enrolment, 6- and 12-month cohorts included 2794, 1310 and 629 patients, respectively. At enrolment, 24% of patients had a BSA ≤ 1% and 41% a BSA ≤ 3%. In the 6-month cohort, 43%/64% had a BSA ≤ 1%/BSA ≤ 3%. In the 12-month cohort, 46%/69% of patients had a BSA ≤ 1%/BSA ≤ 3%. Patients not at target/acceptable criteria had higher odds for worse quality of life compared with those who were. CONCLUSION: While most patients at 6- and 12-month visits were at the 'acceptable' response, less than half were at the 'target' response despite systemic therapy. There remain unmet needs to optimize psoriasis therapy and further validate current treat-to-target guidelines.

Ninety years of change on a low wooded island, Great Barrier Reef.

We assess 90 years of change on a Low Wooded Island (Low Isles, Great Barrier Reef), employing drones and topographic profiling to accurately survey ramparts, mangroves, the reef flat and the sand cay. A comparison with maps from the 1928-1929 Great Barrier Reef Expedition revealed the redistribution of an outer rampart and inward movement of shingle ridges. Remarkable lateral expansion of the mangrove woodland some 400 m has occurred as carbonate sand deposition has increased reef flat elevation, obscuring coral microatolls. The sand cay has stayed relatively constant in size, moving approximately 44 m in a northeasterly direction and rotating slightly. We conclude that the existing configuration of landforms probably represents an equilibrium with local biophysical conditions, including sea level, wave dynamics, vegetation growth, storms and cyclones. The variable nature of ramparts and the presence of a trough that prevents the continuous spread of mangroves across a uniformly flat colonization surface precludes the interpretation of landform changes with respect to a geomorphic evolutionary sequence. Moreover, longer-term implications of environmental change for these landforms can only be evaluated once the specific nature of the local carbonate budget, including the relative contribution of corals, foraminifera and Halimeda has been elucidated.

Perforated diverticulitis in the North of England: trends in patient outcomes, management approach and the influence of subspecialisation.

INTRODUCTION: In recent years, several management options have been used in the management of perforated diverticulitis, ranging from conservative treatment to laparotomy. General surgery has also become increasingly specialised over time. This retrospective cohort study investigated changes in patient outcomes following perforated diverticulitis, management approach and the influence of consultant subspecialisation over time. MATERIALS AND METHODS: Data was collected on patients admitted with perforated diverticulitis in the North of England between 2002 and 2016. Subspecialisation was categorised as colorectal or other general subspecialties. The primary outcome of interest was overall 30-day mortality; secondary outcomes included surgical approach, stoma and anastomosis rate. RESULTS: A total of 3394 cases of perforated diverticulitis were analysed (colorectal, n = 1290 and other subspecialists, n = 2104) with a 30-day mortality of 11.6%. There was a significant reduction in mortality over time (2002-2006: 18.6% to 2012-2016: 6.8, P < 0.001).There was a significant reduction in open surgery (60% to 25.3%, P < 0.001) with increased conservative management (37.4% to 63.5%, P < 0.001), laparoscopic resection (0.1% to 4.9%, P < 0.001) and laparoscopic washout (0.1% to 5.7%, P < 0.001).Patients admitted under colorectal surgeons had lower mortality than other subspecialists (9.9% vs 12.4%, P = 0.027), which remained significant following multivariate adjustment (hazard ratio 1.44, P = 0.039). These patients had fewer stomas (13.9% vs. 21.0%, P = 0.001) and higher anastomosis rates (22.1% vs 15.8%, P = 0.004). CONCLUSION: This study demonstrated considerable improvements in the management of perforated diverticulitis alongside the positive impact of subspecialisation on patient outcomes.

Short- and long-term clinical and patient-reported outcomes following laparoscopic ventral mesh rectopexy using biological mesh for pelvic organ prolapse: a prospective cohort study of 224 consecutive patients.

AIM: Laparoscopic ventral mesh rectopexy (LVMR) is potentially a safe and effective operation to correct pelvic organ prolapse and to treat obstructive defaecation and solitary rectal ulcer syndrome. This study aimed to evaluate, in a prospective, consecutive cohort of patients, the long-term clinical outcomes following LVMR, patient-reported functional and quality of life outcomes, and urinary and sexual dysfunction. METHOD: Data on 224 patients who underwent LVMR with Permacol™ biological mesh were collected prospectively from May 2008 to October 2016. Outcome measures were complications, recurrence, mortality, patient satisfaction, patient-reported functional and quality of life outcomes, and urinary and sexual dysfunction. Scores were compared using the two-tailed Wilcoxon signed rank test. P < 0.05 was considered statistically significant. RESULTS: There was no mortalities associated with LVMR in this series; complications occurred in 10.7% of patients (4.9% early, 5.8% late). Mesh-related morbidity was 0.45% and vaginal suture-related morbidity was 1.33%. Recurrence occurred in 25 patients (11.4%), 5% at 12 months, 10.7% at 5 years. Significant improvement in patient-reported functional outcomes were seen (P < 0.001) for both constipation and faecal incontinence symptoms. Furthermore, significant improvement in quality of life outcomes for patients with constipation, faecal incontinence and prolapse persisted through follow-up (P < 0.001). Patient satisfaction was positive for > 90% of patients during follow-up. Symptoms of stress urinary incontinence, urge incontinence and dyspareunia improved significantly postoperatively (P < 0.001). CONCLUSION: LVMR using Permacol is associated with low morbidity and mortality, recurrence and, additionally, significantly improved constipation, faecal incontinence and prolapse functional and quality of life outcomes, with associated improvement in urogynaecological symptoms.

Treatment of low bone density or osteoporosis to prevent fractures in men and women: a clinical practice guideline update from the American College of Physicians

DESCRIPTION: This guideline updates the 2008 American College of Physicians (ACP) recommendations on treatment of low bone density and osteoporosis to prevent fractures in men and women. This guideline is endorsed by the American Academy of Family Physicians. METHODS: The ACP Clinical Guidelines Committee based these recommendations on a systematic review of randomized controlled trials; systematic reviews; large observational studies (for adverse events); and case reports (for rare events) that were published between 2 January 2005 and 3 June 2011. The review was updated to July 2016 by using a machine-learning method, and a limited update to October 2016 was done. Clinical outcomes evaluated were fractures and adverse events. This guideline focuses on the comparative benefits and risks of short- and long-term pharmacologic treatments for low bone density, including pharmaceutical prescriptions, calcium, vitamin D, and estrogen. Evidence was graded according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. TARGET AUDIENCE AND PATIENT POPULATION: The target audience for this guideline includes all clinicians. The target patient population includes men and women with low bone density and osteoporosis. RECOMMENDATION 1: ACP recommends that clinicians offer pharmacologic treatment with alendronate, risedronate, zoledronic acid, or denosumab to reduce the risk for hip and vertebral fractures in women who have known osteoporosis. (Grade: strong recommendation; high-quality evidence). RECOMMENDATION 2: ACP recommends that clinicians treat osteoporotic women with pharmacologic therapy for 5 years. (Grade: weak recommendation; low-quality evidence). RECOMMENDATION 3: ACP recommends that clinicians offer pharmacologic treatment with bisphosphonates to reduce the risk for vertebral fracture in men who have clinically recognized osteoporosis. (Grade: weak recommendation; low-quality evidence). RECOMMENDATION 4: ACP recommends against bone density monitoring during the 5-year pharmacologic treatment period for osteoporosis in women. (Grade: weak recommendation; low-quality evidence). RECOMMENDATION 5: ACP recommends against using menopausal estrogen therapy or menopausal estrogen plus progestogen therapy or raloxifene for the treatment of osteoporosis in women. (Grade: strong recommendation; moderate-quality evidence). RECOMMENDATION 6: ACP recommends that clinicians should make the decision whether to treat osteopenic women 65 years of age or older who are at a high risk for fracture based on a discussion of patient preferences, fracture risk profile, and benefits, harms, and costs of medications. (Grade: weak recommendation; low-quality evidence).

Differential antibody responses to gliadin-derived indigestible peptides in patients with schizophrenia.

Gluten consumption has previously been implicated in the development of schizophrenia while an immunological link between gluten and schizophrenia was established by the detection of circulating antibodies against gliadin, a major component of wheat gluten. Several studies have reported an increase in circulating antibodies against native gliadin molecules that are unlikely to survive degradation in the digestive system. In this study, therefore, we measured plasma immunoglobulin G (IgG) and IgA antibodies against indigestible gliadin-derived peptide antigens using an in-house enzyme-linked immunosorbent assay (ELISA) among 169 patients with schizophrenia and 236 control subjects. We also examined the plasma levels of IgG and IgA antibodies against the mixture of native gliadins using commercially available ELISA kits. The results showed that patients with schizophrenia had the increased levels of plasma IgG against the γ-gliadin-derived fragment, namely AAQ6C, but decreased levels of plasma IgG against the α- and γ3-gliadin-derived antigens, as compared with control subjects. This study also demonstrated a uniform decrease in plasma IgA antibodies against gliadin-derived antigens. There was no significant difference in the levels of plasma antibodies against native gliadins between the patient group and the control group. Of eight gliadin-derived antigens tested, four showed a sensitivity of >20% against the specificity of ⩾95% for detection of their corresponding antibodies in plasma. These four tests may thus have a potential to serve as biomarkers for the identification of schizophrenia subgroups that may need an alternative therapy or precision treatment. Further investigation with clinical trials should be carried out to explore this possibility.

Noninvasive treatments for acute, subacute, and chronic low back pain: a clinical practice guideline from the American College of Physicians

DESCRIPTION: The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on noninvasive treatment of low back pain. METHODS: Using the ACP grading system, the committee based these recommendations on a systematic review of randomized, controlled trials and systematic reviews published through April 2015 on noninvasive pharmacologic and nonpharmacologic treatments for low back pain. Updated searches were performed through November 2016. Clinical outcomes evaluated included reduction or elimination of low back pain, improvement in back-specific and overall function, improvement in health-related quality of life, reduction in work disability and return to work, global improvement, number of back pain episodes or time between episodes, patient satisfaction, and adverse effects. TARGET AUDIENCE AND PATIENT POPULATION: The target audience for this guideline includes all clinicians, and the target patient population includes adults with acute, subacute, or chronic low back pain. RECOMMENDATION 1: Given that most patients with acute or subacute low back pain improve over time regardless of treatment, clinicians and patients should select nonpharmacologic treatment with superficial heat (moderate-quality evidence), massage, acupuncture, or spinal manipulation (low-quality evidence). If pharmacologic treatment is desired, clinicians and patients should select nonsteroidal anti-inflammatory drugs or skeletal muscle relaxants (moderate-quality evidence). (Grade: strong recommendation). RECOMMENDATION 2: For patients with chronic low back pain, clinicians and patients should initially select nonpharmacologic treatment with exercise, multidisciplinary rehabilitation, acupuncture, mindfulness-based stress reduction (moderate-quality evidence), tai chi, yoga, motor control exercise, progressive relaxation, electromyography biofeedback, low-level laser therapy, operant therapy, cognitive behavioral therapy, or spinal manipulation (low-quality evidence). (Grade: strong recommendation). RECOMMENDATION 3: In patients with chronic low back pain who have had an inadequate response to nonpharmacologic therapy, clinicians and patients should consider pharmacologic treatment with nonsteroidal anti-inflammatory drugs as first-line therapy, or tramadol or duloxetine as second-line therapy. Clinicians should only consider opioids as an option in patients who have failed the aforementioned treatments and only if the potential benefits outweigh the risks for individual patients and after a discussion of known risks and realistic benefits with patients. (Grade: weak recommendation, moderate-quality evidence).

Polyketide and nonribosomal peptide retro-biosynthesis and global gene cluster matching.

Polyketides (PKs) and nonribosomal peptides (NRPs) are profoundly important natural products, forming the foundations of many therapeutic regimes. Decades of research have revealed over 11,000 PK and NRP structures, and genome sequencing is uncovering new PK and NRP gene clusters at an unprecedented rate. However, only ∼10% of PK and NRPs are currently associated with gene clusters, and it is unclear how many of these orphan gene clusters encode previously isolated molecules. Therefore, to efficiently guide the discovery of new molecules, we must first systematically de-orphan emergent gene clusters from genomes. Here we provide to our knowledge the first comprehensive retro-biosynthetic program, generalized retro-biosynthetic assembly prediction engine (GRAPE), for PK and NRP families and introduce a computational pipeline, global alignment for natural products cheminformatics (GARLIC), to uncover how observed biosynthetic gene clusters relate to known molecules, leading to the identification of gene clusters that encode new molecules.

Retrospective analysis of 30-day mortality for emergency general surgery admissions evaluating the weekend effect.

BACKGROUND: The weekend effect describes excess mortality associated with hospital admission on Saturday or Sunday. This study assessed whether a weekend effect exists for patients admitted for emergency general surgery. METHODS: Data for emergency general surgical admissions to National Health Service hospitals in the Northern Deanery in England between 2000 and 2014 were collected, including demographics, co-morbidities, diagnoses, operations undertaken and outcomes. The primary outcome of interest was in-hospital death within 30 days of admission. Cox regression analysis was undertaken with adjustment for co-variables. RESULTS: There were 12 100 in-hospital deaths within 30 days of admission (3·3 per cent). The overall 30-day mortality rate reduced significantly during the 15-year interval studied, from 5·4 per cent (2000-2004) to 4·0 per cent (2005-2009) and 2·9 per cent during 2010-2014 (P < 0·001). There was no significant mortality difference for patients admitted at the weekend in adjusted Cox models (hazard ratio (HR) 1·00 for Saturday and 0·90 for Sunday, versus Wednesday). There was a significantly higher mortality for operations undertaken at the weekend (HR 1·15 for Saturday and 1·40 for Sunday; P = 0·021 and P < 0·001 respectively). The significantly increased mortality that was evident for emergency surgery at the weekend compared with weekdays in 2000-2004 (HR 1·46 for Saturday and 1·55 for Sunday; both P < 0·001); had reduced by 2010-2014, when the adjusted mortality risk was not significant (HR 1·18 for Saturday and 1·12 for Sunday). CONCLUSION: During the past 15 years there has been a weekend effect in patients undergoing emergency general surgery based on day of operation, but not day of admission. Overall mortality for emergency general surgery has improved significantly, and in the past 5 years the increased mortality risk of weekend surgery has reduced.

Attrition and weight loss outcomes for patients with complex obesity, anxiety and depression attending a weight management programme with targeted psychological treatment.

The objective of the study is to investigate the effect of baseline anxiety and depression, using different definitions for caseness, on attrition and weight outcomes following a multidisciplinary weight management programme. The study design is a prospective observational study. The Hospital Anxiety and Depression Scale (HADS) was used to measure anxiety and depression with 'caseness' scoring ≥11 and severity ≥14. The participants were all patients who began a weight management programme between 1 October 2008 and 30 September 2009 (n = 1838). The setting was the Glasgow and Clyde Weight Management Service (GCWMS), a specialist multidisciplinary service, which aims to achieve a minimum of ≥5 kg weight loss. The results were as follows: patients with HADS score ≥14 were referred to the integrated psychology service for psychological assessment or intervention. Patients with caseness (HADS ≥11) for anxiety (33%) and depression (27%) were significantly younger, heavier, more socio-economically deprived and a higher proportion was female. There was a significant positive correlation between HADS anxiety and depression scores and increasing body mass index (r(2) = 0.094, P < 0.001 and r(2) = 0.175, P < 0.001, respectively). Attendance and completion was lower throughout follow-up amongst patients with anxiety or depression. More patients with HADS score ≥11 achieved ≥5 kg or ≥5% weight loss and by 12 months those with anxiety had a significantly higher mean weight loss (P = 0.032). Participants who scored for severe anxiety (HADS ≥14) achieved similar weight loss to those without, whilst participants who scored for severe depression achieved significantly greater weight loss than non-cases at 3, 6 and 12 months of follow-up (P < 0.01). Despite a less favourable case-mix of risk-factors for poor weight loss, patients who scored caseness for severe anxiety or depression and were offered additional psychological input achieved similar or better weight loss outcomes.

Localised mitogenic activity in horses following infection with Streptococcus equi.

Streptococcus equi subspecies equi (S. equi) is the causative agent of strangles, a highly contagious upper respiratory disease of equids. Streptococcus equi produces superantigens (sAgs), which are thought to contribute to strangles pathogenicity through non-specific T-cell activation and pro-inflammatory response. Streptococcus equi infection induces abscesses in the lymph nodes of the head and neck. In some individuals, some abscess material remains into the guttural pouch and inspissates over time to form chondroids which can harbour live S. equi. The aim of this study was to determine the sites of sAg production during infection and therefore improve our understanding of their role. Abscess material, chondroids and serum collected from Equidae with signs of strangles were tested in mitogenic assays. Mitogenic sAg activity was only detected in abscess material and chondroids. Our data support the localised in vivo activity of sAg during both acute and carrier phases of S. equi infection.

[Postvaccinal fatal Streptococcus zooepidemicus necrotizing fasciitis in a young dog: a case report]. / Fatale necrotiserende fasciitis door Strepto- coccus zooepidemicus na vaccinatie bij een jonge hond, een case report.

A 2.5-years-old female mongrel dog was routinely subcutaneously vaccinated. A few hours later mental dullness was noticed by the owner progressing into stupor the next day and resulting in a comatose state and death within 48 hours after vaccination. At post mortem examination, which was extended with histology and bacteriology, a necrotizing fasciitis and bacteremia caused by Streptococcus equi subsp. zooepidemicus were established. In the isolated Streptococcus strain four different superantigens were demonstrated that appeared to be able to produce exotoxins in vitro. Therefore, it is concluded that the minor skin trauma caused by vaccination enabled this strain to gain access to the subcutaneous tissue and to induce a necrotizing fasciitis. This process was complicated with a bacterial septicemia leading to death of the dog within 48 hours.