Anatomy and resilience of the global production ecosystem.

Much of the Earth's biosphere has been appropriated for the production of harvestable biomass in the form of food, fuel and fibre. Here we show that the simplification and intensification of these systems and their growing connection to international markets has yielded a global production ecosystem that is homogenous, highly connected and characterized by weakened internal feedbacks. We argue that these features converge to yield high and predictable supplies of biomass in the short term, but create conditions for novel and pervasive risks to emerge and interact in the longer term. Steering the global production ecosystem towards a sustainable trajectory will require the redirection of finance, increased transparency and traceability in supply chains, and the participation of a multitude of players, including integrated 'keystone actors' such as multinational corporations.

Effect of 12-months testosterone replacement therapy on bone mineral density and markers of bone turnover in testicular cancer survivors - results from a randomized double-blind trial.

BACKGROUND: Testicular cancer survivors (TCS) are at risk of Leydig cell insufficiency, which is a condition characterized by elevated luteinising hormone (LH) in combination with low levels of testosterone. It has been suggested that this condition is associated with impaired metabolic profile and low bone mineral density (BMD). The primary aim of the randomized double-blind trial NCT02991209 was to evaluate metabolic profile after 12-months testosterone replacement therapy (TRT) in TCS with mild Leydig cell insufficiency. Here we present the secondary outcomes of changes in BMD and markers of bone turnover. METHODOLOGY: In total, 69 TCS with mild Leydig cell insufficiency were randomized 1:1 to 12 months TRT (n = 35) (Tostran, gel, 2%, applied transdermally, with a maximum daily dose of 40 mg) or placebo (n = 34). BMD and markers of bone turnover were evaluated at baseline, after 6- and 12-months TRT, and 3-months post-treatment. Linear mixed effects models were used to analyse changes in BMD, N-terminal propeptide of type 1 procollagen (P1NP) and C-terminal telopeptide of type I collagen (CTX). RESULTS: After 12 months treatment, TRT was not associated with a statistically significant difference in BMD compared to placebo; total body BMD: 0.01 g/cm2 (95% confidence interval (CI): -0.01 - 0.02), BMD of the lumbar spine: 0.01 g/cm2, (95% CI: -0.01-0.03), BMD of the left femoral neck: 0.00, (95% CI: -0.01-0.02). TRT was associated with a small but statistically significant increase in P1NP: 11.65 µg/L (95% CI: 3.96, 19.35), while there was no difference in CTX. CONCLUSION: 12 months of TRT did not change BMD, while there was as small and clinically irrelevant increase in P1NP compared to placebo in TCS with mild Leydig cell insufficiency. The findings need validation in a larger cohort.

Clinical insight among persons with schizophrenia spectrum disorders treated with amisulpride, aripiprazole or olanzapine: a semi-randomised trial.

BACKGROUND: Antipsychotic treatment may improve clinical insight. However, previous studies have reported inconclusive findings on whether antipsychotics improve insight over and above the reduction in symptoms of psychosis. These studies assessed homogeneous samples in terms of stage of illness. Randomised studies investigating a mixed population of first- and multiepisode schizophrenia spectrum disorders might clarify this disagreement. METHODS: Our data were derived from a pragmatic, rater-blinded, semi-randomised trial that compared the effectiveness of amisulpride, aripiprazole and olanzapine. A sample of 144 patients with first- or multiepisode schizophrenia spectrum disorders underwent eight assessments during a 1-year follow-up. Clinical insight was assessed by item General 12 from the Positive and Negative Syndrome Scale (PANSS). We analysed latent growth curve models to test if the medications had a direct effect on insight that was over and above the reduction in total psychosis symptoms. Furthermore, we investigated whether there were differences between the study drugs in terms of insight. RESULTS: Based on allocation analysis, all three drugs were associated with a reduction in total psychosis symptoms in the initial phase (weeks 0-6). Amisulpride and olanzapine were associated with improved insight over and above what was related to the reduction in total psychosis symptoms in the long-term phase (weeks 6-52). However, these differential effects were lost when only including the participants that chose the first drug in the randomisation sequence. We found no differential effect on insight among those who were antipsychotic-naïve and those who were previously medicated with antipsychotics. CONCLUSIONS: Our results suggest that antipsychotic treatment improves insight, but whether the effect on insight surpasses the effect of reduced total psychosis symptoms is more uncertain. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01446328, 05.10.2011.

When does shared decision making is adopted in psychiatric clinical practice? Results from a European multicentric study.

To identify factors associated with the use of shared decision making in routine mental health care in a large multicenter European study. Data have been collected within the study "Clinical decision making and outcome in routine care for people with severe mental illness" (CEDAR), which is a naturalistic, longitudinal, observational study carried out in six European countries. Patients with a severe mental illness attending outpatient units and their treating clinicians have been recruited. Clinicians' Clinical Decision Making (CDM) styles have been explored through the Clinical Decision Making Style Scale. Patients' clinical and social outcomes have been assessed through validated assessment instruments. The sample consisted of 588 patients and 213 professionals. Professionals were mainly psychiatrists (35.7%), nurses (21.6%), support workers, social workers or occupational therapists (24.9%), psychologists (9.9%) or trainees in psychiatry (4.7%). In the majority of cases, clinicians adopted a shared CDM style. Shared CDM was more frequently adopted with patients with psychotic disorders, with a better quality of life and social functioning. At multivariate analyses, the likelihood of adopting shared decision making increased in patients with higher levels of interpersonal relationships' skills (p < 0.05) and global functioning (p < 0.01). On the contrary, being a trainee in psychiatry reduced the likelihood of adopting shared CDM (p < 0.008). Shared decision making has been adopted mainly when patients have a better functioning and less severe clinical symptomatology and by less trained clinicians, differently from national and international recommendations. More efforts should be made to implement interventions to promote shared CDM, with a specific focus for trainees in psychiatry.

Local recurrence rate in a national Danish patient cohort after curative treatment for rectal cancer.

AIM: Several trials have shown that preoperative (chemo)radiotherapy (CRT) reduces local recurrence rates (LRRs) in rectal cancer (RC). The use of CRT varies greatly between countries. It is unknown whether the restrictive use of CRT in Denmark results in a higher LRR relative to other countries. The aim was to evaluate the LRR in a national Danish consecutive cohort of patients with RC. METHODS: All data from patients with RC in Denmark in 2009-2010 who were operated on with curative intent were retrieved from the Danish Colorectal Cancer Group database. Patients with metastases at the time of diagnosis, patients with synchronous colon cancer, and patients, in whom only local surgical procedures were performed, were excluded. In total, 1633 patients met the inclusion criteria. Clinical follow-up was at least five years with a cut-off date of 31 December 2015. RESULTS: Clinical follow-up was 5.4 years (median) with an interquartile range of 4.5-6.1 years. Of all included patients, 479 (29%) were treated with preoperative long-course CRT. Local recurrence was found in 68 patients, resulting in an LRR of 4.2%, and 182 (11%) patients developed distant metastases. Five-year overall survival was 74% (95% CI: 71.64-75.91). CONCLUSIONS: Five-year follow-up of curatively treated patients with RC in Denmark revealed a low LRR. This figure is identical to those reported in other Nordic countries, despite Denmark's considerably stricter guidelines for CRT. The obtained results justify the currently adopted restrictive use of preoperative CRT in Denmark.

Near-normalization of glycaemic control with glucagon-like peptide-1 receptor agonist treatment combined with exercise in patients with type 2 diabetes.

AIMS: To investigate the effects of exercise in combination with a glucagon-like peptide-1 receptor agonist (GLP-1RA), liraglutide, or placebo for the treatment of type 2 diabetes. METHODS: Thirty-three overweight, dysregulated and sedentary patients with type 2 diabetes were randomly allocated to 16 weeks of either exercise and liraglutide or exercise and placebo. Both groups had three supervised 60-minute training sessions per week including spinning and resistance training. RESULTS: Glycated haemoglobin (HbA1c) levels dropped by a mean ± standard deviation of 2.0% ± 1.2% (from 8.2% ± 1.4%) in the exercise plus liraglutide group vs 0.3% ± 0.9% (from 8.0% ± 1.2%) in the exercise plus placebo group ( P < .001), and body weight was reduced more with liraglutide (-3.4 ± 2.9 kg vs -1.6 ± 2.3 kg; P < .001). Compared with baseline, similar reductions were seen in body fat (exercise plus liraglutide: -2.5% ± 1.4% [ P < .001]; exercise plus placebo: -2.2% ± 1.9% [ P < .001]) and similar increases were observed in maximum oxygen uptake (exercise plus liraglutide: 0.5 ± 0.5 L O2 /min [ P < .001]; exercise plus placebo: 0.4 ± 0.4 L O2 /min [ P = .002]). Greater reductions in fasting plasma glucose (-3.4 ± 2.3 mM vs -0.3 ± 2.6 mM, P < .001) and systolic blood pressure (-5.4 ± 7.4 mm Hg vs -0.6 ± 11.1 mm Hg, P < .01) were seen with exercise plus liraglutide vs exercise plus placebo. The two groups experienced similar increases in quality of life during the intervention. CONCLUSIONS: In obese patients with type 2 diabetes, exercise combined with GLP-1RA treatment near-normalized HbA1c levels and caused a robust weight loss when compared with placebo. These results suggest that a combination of exercise and GLP-1RA treatment is effective in type 2 diabetes.

Are assisted reproduction technologies associated with categorical or dimensional aspects of psychopathology in childhood, adolescence or early adulthood? Results from a Danish prospective nationwide cohort study.

An increasing number of children are conceived using assisted reproduction technologies (ART), but little is known about the long-term risk in terms of mental health outcomes. All twin and singleton children conceived via ART and born in 1995 were sampled from the Danish in vitro fertilization registry and matched to four spontaneously conceived (SC) children. The children were followed-up at the age of 3, 7, 14 and 18 years in the Danish Psychiatric Central Research Registry, to estimate the prevalence of all possible psychiatric diagnoses; dimensional aspects of psychopathology were assessed at the age of 14 years, using the Child Behavior Checklist (CBCL). The study included 858 ART children and 3436 SC children. ART and SC children were not clinically distinguishable on either the categorical measures of psychopathology at the age of 3, 7, 14 and 18 years, or on CBCL scale scores at the age of 14 years. The findings remained nonsignificant after controlling for sample differences. This large, prospective, nationwide cohort study provides evidence to support that ART exposure does not increase the risk of adverse mental health outcomes considered as a whole, while power was limited to discard an effect of ART on specific mental health disorders.

A plant growth form dataset for the New World.

This dataset provides growth form classifications for 67,413 vascular plant species from North, Central, and South America. The data used to determine growth form were compiled from five major integrated sources and two original publications: the Botanical Information and Ecology Network (BIEN), the Plant Trait Database (TRY), the SALVIAS database, the USDA PLANTS database, Missouri Botanical Garden's Tropicos database, Wright (2010), and Boyle (1996). We defined nine plant growth forms based on woodiness (woody or non-woody), shoot structure (self-supporting or not self-supporting), and root traits (rooted in soil, not rooted in soil, parasitic or aquatic): Epiphyte, Liana, Vine, Herb, Shrub, Tree, Parasite, or Aquatic. Species with multiple growth form classifications were assigned the growth form classification agreed upon by the majority (>2/3) of sources. Species with ambiguous or otherwise not interpretable growth form assignments were excluded from the final dataset but are made available with the original data. Comparisons with independent estimates of species richness for the Western hemisphere suggest that our final dataset includes the majority of New World vascular plant species. Coverage is likely more complete for temperate than for tropical species. In addition, aquatic species are likely under-represented. Nonetheless, this dataset represents the largest compilation of plant growth forms published to date, and should contribute to new insights across a broad range of research in systematics, ecology, biogeography, conservation, and global change science.

Depression and the risk of autoimmune disease: a nationally representative, prospective longitudinal study.

BACKGROUND: Autoimmune diseases are associated with substantial morbidity and mortality, yet the etiology remains unclear. Depression has been implicated as a risk factor for various immune-related disorders but little is known about the risk of autoimmune disease. This study examined the association between depression and the risk of autoimmune disease, and investigated the temporal and dose-response nature of these relationships. METHOD: A prospective population-based study including approximately 1.1 million people was conducted using linked Danish registries. Depression and autoimmune diseases were diagnosed by physicians and documented in medical records. In total, 145 217 individuals with depression were identified between 1995 and 2012. Survival analyses were used to estimate the relative risk of autoimmune disease among those with, compared to without, depression. Analyses were adjusted for gender, age, and co-morbid mental disorders. RESULTS: Depression was associated with a significantly increased risk of autoimmune disease [incidence rate ratio (IRR) 1.25, 95% CI 1.19-1.31], compared to those without a history of depression. Results suggest a general increased risk of autoimmune diseases following the onset of depression during first year (IRR 1.29, 95% CI 1.05-1.58), which remained elevated for the ensuing 11 years and beyond (IRR 1.53, 95% CI 1.34-1.76). Findings did not support a dose-response relationship. CONCLUSIONS: Depression appears to be associated with an increased risk of a range of autoimmune diseases. Depression may play a role in the etiology of certain autoimmune conditions. If replicated, findings could highlight additional clinical implications in the treatment and management of depression. Future studies are needed to investigate the possible social, genetic, and neurobiological underpinnings of these relationships.

The gap between available knowledge and its use in clinical psychiatry.

OBJECTIVE: The time span between knowledge becoming available and its integration into daily clinical routine is lengthy. This phenomenon is explored in this study. METHOD: We used the outcomes of our activities for investigating and strengthening the research-based activities to improve physical health in the routines of clinical psychiatric wards as examples for our analyses. RESULTS: The time span between new knowledge becoming available and its implementation into general clinical treatment is very long. However, a shortening of this time span is seen through active leadership backup and clinical research experience among psychiatrists and staff in the wards. In particular, the involvement of medical students interested in clinical research activities seems to have a positive impact. CONCLUSION: Academia needs to be re-implemented into clinical psychiatry. Staff with research experience is needed in all professions to increase evidence-based practice. Leaders must take responsibility for implementing new knowledge into the routines of the department and must support staff in these activities on a daily basis.

Inflammatory bowel disease meta-evidence and its challenges: is it time to restructure surgical research?

AIM: The aim of this study was to compare the methodological quality and input paper characteristics of systematic reviews and meta-analyses reported in the medical and surgical literature by performing a systematic 'overview of reviews'. Ulcerative colitis (UC) and Crohn's disease (CD) were used as the framework for this comparison as they are relatively common serious conditions, with both medical and surgical options for therapy. METHOD: Medline, Embase, CINHAL and the Cochrane Database were searched to November 2013. Eligible papers were systematic reviews or meta-analyses that considered a question of therapy in CD or UC. Two independent reviewers selected the papers, extracted the data and scored their methodology using the AMSTAR scoring system. The papers were categorized into medical therapy (M), surgical therapy (S) or medical and surgical therapy (MS) groups. Following retrieval of the sample of meta-evidence papers, the original input studies used in their creation were identified and a search of Medline, Embase, CINHAL and the Cochrane Database was performed. A team of researchers then examined the collection of papers for bibliographic and financial information. RESULTS: Five hundred papers were identified in the meta-evidence search, of which 118 were deemed eligible. There was a difference in the AMSTAR-rated average quality of the papers between the S and M group (S 7.36 vs M 8.75, P = 0.01). On average S papers were published in journals with a lower impact factor (S 3.26, M 5.04, MS 5.30, P < 0.001). S papers also showed more heterogeneity (I(2) ; S 37%, M 24%, MS 10%, P < 0.001). Some 25% of S meta-analyses used data-sets with significant heterogeneity (I(2) > 75%), compared with 8% of M meta-analyses and 3% of the MS meta-analyses. Some 5% of S papers were done on data sets that had I(2) values > 90%. There was no difference in the average number of papers assessed in each group, the average number of patients per meta-paper, the average time covered by the reviews, the average number of papers considered within each meta-analysis, or the average number of patients considered within each meta-analysis. Considering the conclusions of each meta-analysis, S meta-evidence was 50% more likely than M meta-evidence to be unable to make recommendations for practice. A total of 1499 original input papers were identified, of which 283 were used in more than one review. Within the non-repeated papers (n = 1023) the average impact factor within the S group was lower than that of the M and the MS groups (3.720 vs 11.230 vs 7.563, respectively; ANOVAP < 0.001). M papers had higher rates of pharmaceutical sponsorship than S papers (M 56% vs S 1%) and twice the level of government support (M 16% vs S 8%). Of note, 21% of M papers had corporate sponsorship but did not list any conflict of interest. CONCLUSION: Compared with M meta-analyses, S meta-analyses in the UC and CD domain are more likely to be of poorer methodological quality, are of a greater degree of heterogeneity and less often offer a positive conclusion. The papers used to generate meta-evidence in M papers have a greater degree of corporate and government sponsorship, and are more likely to come from journals with higher impact factors.

EAACI food allergy and anaphylaxis guidelines: managing patients with food allergy in the community.

The European Academy of Allergy and Clinical Immunology (EAACI) Food Allergy and Anaphylaxis Guidelines, managing patients with food allergy (FA) in the community, intend to provide guidance to reduce the risk of accidental allergic reactions to foods in the community. This document is intended to meet the needs of early-childhood and school settings as well as providers of non-prepackaged food (e.g., restaurants, bakeries, takeaway, deli counters, and fast-food outlets) and targets the audience of individuals with FA, their families, patient organizations, the general public, policymakers, and allergists. Food allergy is the most common trigger of anaphylaxis in the community. Providing children and caregivers with comprehensive information on food allergen avoidance and prompt recognition and management of allergic reactions are of the utmost importance. Provision of adrenaline auto-injector devices and education on how and when to use these are essential components of a comprehensive management plan. Managing patients at risk of anaphylaxis raises many challenges, which are specific to the community. This includes the need to interact with third parties providing food (e.g., school teachers and restaurant staff) to avoid accidental exposure and to help individuals with FA to make safe and appropriate food choices. Education of individuals at risk and their families, their peers, school nurses and teachers as well as restaurant and other food retail staff can reduce the risk of severe/fatal reactions. Increased awareness among policymakers may improve decision-making on legislation at local and national level.

Fifty years' development and future perspectives of psychiatric register research.

OBJECTIVE: This article illustrates the development of psychiatric register research and discusses the strengths, limitations, and possible directions for future activities. METHOD: Examples illustrating the development from the post-World War II introduction of psychiatric register research until today are selected. RESULTS: The strengths of register research are seen especially within health service. Until recently, when starting linking registers to biobanks, register research had limited value in cause-seeking. Register research benefits from the possibilities for following identifiable persons over long time (lifelong) and the possibilities for linking to other registers and databases. Important limitations of register research are the heterogeneity and questionable validity of the clinical data collected. CONCLUSION: Future register research can go in the direction of big is beautiful collecting data from all possible sources creating giga-registers. In that case, low data quality will still be an unsolved problem. Or it can take the direction of smaller local clinical databases which has many advantages, for example, integrating clinical knowledge and experience into register research. However, in that case, registers will not be able to deal with rare conditions and diseases.

National and international guidelines for rectal cancer.

AIM: Rectal cancer is a common malignancy. Differences in daily practice may influence the morbidity and mortality, and many national and international organizations have created guidelines for staging and treatment of rectal cancer. Even though consensus is reached within individual guidelines, this might not be the case between guidelines. No formal evaluation of the contrasting guidance has been reported. METHOD: A systematic search for national and international guidelines on rectal cancer was performed. Eleven guidelines were identified for further analysis. RESULTS: There was no consensus concerning the definition of rectal cancer. Ten of the 11 guidelines use the TNM staging system and there was general agreement regarding the recommendation of MRI and CT in rectal cancer. There was consensus concerning a multidisciplinary approach, preoperative chemoradiotherapy (CRT) and total mesorectal excision (TME). There was no consensus concerning local treatment of T1 tumours and adjuvant therapy, and not all guidelines included metastatic disease and recurrence. There was no consensus on the protocol for follow up. The guidelines had different approaches to evidence. All referred to evidence but not all considered the level of evidence. CONCLUSION: The intention of the study was to provide an overview of international guidelines for rectal cancer based on the underlying evidence, but despite hard evidence it was very difficult to reach general conclusions. Despite much knowledge, there is no international consensus on guidelines for the staging and treatment of rectal cancer.

Pelvic floor reconstruction with a biological mesh after extralevator abdominoperineal excision leads to few perineal hernias and acceptable wound complication rates with minor movement limitations: single-centre experience including clinical examination and interview.

AIM: The aim of the study was to describe long-term subjective and objective results of pelvic floor reconstruction using an absorbable biological mesh after extralevator abdominoperineal excision (ELAPE) for low rectal cancer. METHOD: Records of 53 patients who had an ELAPE with reconstruction of the pelvic floor with a Permacol® mesh between August 2007 and August 2011 were reviewed. Thirty-one of the patients were called for interview and clinical examination. RESULTS: Three (6%) patients developed perineal hernia, 11 had fistulae (nine of which were treated successfully), four patients had a perineal abscess and four patients had superficial wound infections. Removal of the mesh was necessary in one case, while another patient needed implantation of a new mesh. In 13 of the 31 interviewed patients, long-term pain was present, but resolved after a median of 8 months (3-56). No major sitting or movement disabilities were encountered. Three-year survival was 82%, and no local recurrences were found. CONCLUSION: Pelvic floor reconstruction with a biological mesh is a feasible solution when performing ELAPE for low rectal cancer, although long-term pain is a frequent complication.

Result of the implementation of multidisciplinary teams in rectal cancer.

AIM: In 2003 colorectal multidisciplinary teams (MDTs) were established in all major Danish hospitals treating colorectal cancer. The aim was to improve the prognosis by multidisciplinary evaluation and decision about surgical and oncological treatment, based on medical history, clinical examination, imaging, histology and comorbidity. The present study evaluates the effect of the introduction of colorectal MDTs on 1 August 2004 in two Danish hospitals. METHOD: A retrospective cohort study was conducted comparing the outcome during the last 3 years before introduction of MDTs with the first 2 years after (the MDT cohort). The national colorectal cancer database, with follow-up recorded by the National Patient Registry in September 2010 was used. The end-points included the incidence of preoperative radiochemotherapy offered according to the national guidelines, R0/R1/R2 resection, postoperative mortality, local recurrence, distant recurrence and over-all and disease-free survival. RESULTS: Eight hundred and eleven patients were diagnosed with primary rectal cancer in Hvidovre and Bispebjerg hospitals between 1 May 2001 and 31 August 2006. The frequency of preoperative MRI scans increased in the MDT cohort and perioperative mortality decreased. More metachronous distant metastases were found in the MDT cohort but there was no difference in overall survival. CONCLUSION: There was an improved postoperative mortality but no other potential benefits for the patients were seen after the implementation of colorectal MDTs.

Transmission electron microscopy specimen preparation method for multiphase porous functional ceramics.

An optimum method is proposed to prepare thin foil transmission electron microscopy (TEM) lamellae of multiphase porous functional ceramics: prefilling the pore space of these materials with an epoxy resin prior to focused ion beam milling. Several advantages of epoxy impregnation are demonstrated by successful preparation of TEM specimens that maintain the structural integrity of the entire lamella. Feasibility of the TEM alignment procedure is demonstrated, and ideal TEM analyses are illustrated on solid oxide fuel cell and solid oxide electrolysis cell materials. Some potential drawbacks of the TEM specimen preparation method are listed for other samples.

Postoperative morbidity after fast-track laparoscopic resection of rectal cancer.

AIM: Analysis was carried out of the nature and chronological order of early complications after fast-track laparoscopic rectal surgery with a view to optimizing the short-time outcome of rectal cancer surgery. METHOD: A total of 102 consecutive patients who underwent elective fast-track laparoscopic rectal cancer surgery were analysed prospectively from the Danish Colorectal Cancer Database supplemented by data from the medical records. We studied in detail the nature and chronological order of postoperative morbidity and reason for prolonged stay (> 5 days). RESULTS: Twenty-five patients (25%) had one or more complications. Surgical complications occurred in 19 patients, while six patients had medical complications as the primary event. Fifteen patients underwent reoperation, three died, and eight were readmitted within 30 days. The median length of stay was 5 days (range 2-42). CONCLUSION: Postoperative morbidity remains a significant problem in the fast-track era, even in experienced surgical hands. Our results suggest that besides improvement of surgical technique further improvement of outcome lies in early recognition and proper treatment of complications and the perioperative optimization of organ function.