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.

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.

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.

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.

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.

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.

Down but not out: incidence and estimated costs to society of road casualties in Strathclyde, Scotland.

OBJECTIVES: To investigate the recent epidemiological patterns and costs of road traffic casualties (RTCs) in Strathclyde, Scotland. STUDY DESIGN: Retrospective record-linkage epidemiological study using routine data sources. METHODS: A linked police-hospital database was analysed to describe the epidemiology of RTCs from 2004 to 2009. Using UK government methodology, the costs of road casualties to the National Health Service (NHS) and society were assessed. RESULTS: RTC rates declined over the study period. Males were at higher risk than females as were those residing in more socially deprived addresses. The estimated costs of RTCs in Strathclyde amounted to £400 million annually. Of this, around one twentieth (£20 million per year), was attributable to direct NHS costs. CONCLUSIONS: Road casualties remain a major public health threat in Strathclyde, and contribute to health inequalities. RTC costs to society amount to almost a tenth of NHS revenue expenditure. Cost-effective road safety measures should be deployed more widely.

[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.

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 dietary protein reduce hip fracture risk in elders? The Framingham Osteoporosis Study.

UNLABELLED: Association between dietary protein and fracture risk is unclear. We examined association between energy-adjusted protein intake and hip fracture risk in elders. The risk of hip fracture was reduced in upper quartiles of protein intake when compared with lowest quartile. INTRODUCTION: Studies of the association between dietary protein intake and hip fracture risk are conflicting. Therefore, we examined protein intake and hip fracture risk in a population-based group of elderly men and women. METHODS: Five hundred seventy-six women and 370 men from the Framingham Osteoporosis Study with no previous history of hip fracture completed Food Frequency Questionnaires. Energy-adjusted protein intake was evaluated as a continuous variable and as quartiles. Incidence rates and hazard ratios were calculated, adjusting for age, BMI, sex, and energy intake. RESULTS: Among 946 participants (mean age 75 years), mean protein intake was found to be 68 gm/d. Increased protein intake was associated with a decreased risk of hip fracture compared to those in the lowest quartile of protein intake (Q2 HR = 0.70, Q3 HR = 0.56, and Q4 HR = 0.63; all p values ≥ 0.044), p for trend was 0.07. When a threshold effect was considered (Q2-4 vs Q1), intakes in the higher quartiles combined were associated with a significantly lower risk for hip fracture (HR = 0.63; p = 0.04). CONCLUSION: Our results are consistent with reduced risk of hip fracture with higher dietary protein intake. Larger prospective studies are needed to confirm and extend this finding in elderly men and women.

Functional relationships of phytoene synthase 1 alleles on chromosome 7A controlling flour colour variation in selected Australian wheat genotypes.

Flour colour measured as a Commission Internationale de l'Eclairage (CIE) b* value is an important wheat quality attribute for a range of end-products, with genes and enzymes of the xanthophyll biosynthesis pathway providing potential sources of trait variation. In particular, the phytoene synthase 1 (Psy1) gene has been associated with quantitative trait loci (QTL) for flour b* colour variation. Several Psy1 alleles on chromosome 7A (Psy-A1) have been described, along with proposed mechanisms for influencing flour b* colour. This study sought to identify evolutionary relationships among known Psy-A1 alleles, to establish which Psy-A1 alleles are present in selected Australian wheat genotypes and establish their role in controlling variation for flour b* colour via QTL analysis. Phylogenetic analyses showed seven of eight known Psy-A1 alleles clustered with sequences from T. urartu, indicating the majority of alleles in Australian germplasm share a common evolutionary lineage. In this regard, Psy-A1a, Psy-A1c, Psy-A1e and Psy-A1p were common in Australian genotypes with flour b* colour ranging from white to yellow. In contrast Psy-A1s was found to be related to A. speltoides, indicating a possible A-B genome translocation during wheat polyploidisation. A new allele Psy-A1t (similar to Psy-A1s) was discovered in genotypes with yellow flour, with QTL analyses indicating Psy-A1t strongly influences flour b* colour in Australian germplasm. QTL LOD value maxima did not coincide with Psy-A1 gene locus in two of three populations and, therefore, Psy-A1a and Psy-A1p may not be involved in flour colour. Instead two other QTL were identified, one proximal and one distal to Psy-A1 in Australian wheat lines. Comparison of Psy-A1t and Psy-A1p predicted protein sequences suggests differences in putative sites for post-translational modification may influence enzyme activity and subsequent xanthophyll accumulation in the wheat endosperm. Psy-A1a and Psy-A1p were not involved in flour b* colour variation, indicating other genes control variation on chromosome 7A in some wheat genotypes.

Atomic layer deposition ultra-barriers for electronic applications-strategies and implementation.

We show that Al2O3 thin films, grown by atomic layer deposition (ALD) on polyester, are ultrabarriers with moisture permeation <10(-5) g-H2O/m2-day, as determined after aging for more than three years. We present evidence that the mechanism for gas permeation in ALD Al2O3 films is not due to pinholes, but that the onset of permeation occurs abruptly, analogous to electrical breakdown in oxide thin films. We show that the permeation onset time increases for thicker Al2O3 films and higher ALD process temperature, for which the hydrogen defect concentration in Al2O3 films is less. Further, we show that mild plasma treatment of the polyester, prior to ALD deposition of Al2O3, makes the surface more hydrophilic and reduces moisture permeation compared to an untreated surface. Similarly, ALD deposition on the bare or non-slip side of the polyester film is preferred for low permeation.

A large scale quasi-crystalline lamellar lattice in chloroplasts of the green alga Zygnema.

A quasi-crystalline lamellar lattice was observed in chloroplasts of the filamentous green alga Zygnema. The lattice does not appear in the cells until cultures are at the end of the log phase of growth. Pseudograna are also present and become more numerous towards the middle of the log phase. The three-dimensional lattice superficially resembles the configuration of cubic prolamellar bodies but is about 10 times larger and is entirely different in internal structure. The lattice is composed of one or two appressed thylakoids in a stroma matrix which is bounded on each side by a single thylakoid membrane. This multilayered sandwich of membranes and matrix occupies a position equivalent to the single membrane of a cubic prolamellar body.

A room-temperature molecular/organic-based magnet.

The reaction of bis(benzene)vanadium with tetracyanoethylene, TCNE, affords an insoluble amorphous black solid that exhibits field-dependent magnetization and hysteresis at room temperature. The critical temperature could not be estimated as it exceeds 350 kelvin, the thermal decomposition temperature of the sample. The empirical composition of the reported material is V(TCNE)x.Y(CH(2)Cl(2)) with x approximately 2 and Y approximately 1/2. On the basis of the available magnetic and infrared data, threedimensional antiferromagnetic exchange of the donor and acceptor spins resulting in ferrimagnetic behavior appears to be the mode of magnetic coupling.

Review of wheat improvement for waterlogging tolerance in Australia and India: the importance of anaerobiosis and element toxicities associated with different soils.

BACKGROUND AND AIMS: The lack of knowledge about key traits in field environments is a major constraint to germplasm improvement and crop management because waterlogging-prone environments are highly diverse and complex, and the mechanisms of tolerance to waterlogging include a large range of traits. A model is proposed that waterlogging tolerance is a product of tolerance to anaerobiosis and high microelement concentrations. This is further evaluated with the aim of prioritizing traits required for waterlogging tolerance of wheat in the field. METHODS: Waterlogging tolerance mechanisms of wheat are evaluated in a range of diverse environments through a review of past research in Australia and India; this includes selected soils and plant data, including plant growth under waterlogged and drained conditions in different environments. Measurements focus on changes in redox potential and concentrations of diverse elements in soils and plants during waterlogging. KEY RESULTS: (a) Waterlogging tolerance of wheat in one location often does not relate to another, and (b) element toxicities are often a major constraint in waterlogged environments. Important element toxicities in different soils during waterlogging include Mn, Fe, Na, Al and B. This is the first time that Al and B toxicities have been indicated for wheat in waterlogged soils in India. These results support and extend the well-known interactions of salinity/Na and waterlogging/hypoxia tolerance. CONCLUSIONS: Diverse element toxicities (or deficiencies) that are exacerbated during waterlogging are proposed as a major reason why waterlogging tolerance at one site is often not replicated at another. Recommendations for germplasm improvement for waterlogging tolerance include use of inductively coupled plasma analyses of soils and plants.

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.

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.