Structure of trans-bis[4-amino-3,5-bis(pyridin-2-yl)-1,2,4-triazole-N1,N'[diaqua- manganese(II) dibromide

[Mn(C12H10N6)2(H2O)2]Br2, Mr = 727.28, orthorhombic, Pbca, a = 10.734 (6), b = 17.084 (0), c = 15.182 (6) angstrom, V = 2784 angstrom 3, Z = 4, D(x) = 1.734 g cm-3, lambda-(Mo K-alpha) = 0.71073 angstrom, mu = 33.23 cm-1, F(000) = 1450, T = 295 K, final R = 0.032 for 1493 reflections [I > 2-sigma(I)]. The title compound is the first reported mononuclear compound with the ligand 4-amino-3,5-bis(pyridin-2-yl)-1,2,4-triazole. The manganese ions, situated on an inversion centre, are coordinated by four nitrogen atoms with an N-Mn-N angle of 74.1 (1)-degrees and Mn-N distances of 2.188 (4) and 2.266 (4) angstrom. Two axial water molecules [Mn-O = 2.200 (4) angstrom] complete the coordination sphere of the metal, which is pseudo-octahedral. The two bromide ions are not coordinated but are involved in an extended hydrogen-bridging network with the water ligands and the amino group of the triazole

A systematic review of the energy and climate impacts of teleworking

Information and communication technologies (ICTs) increasingly enable employees to work from home and other locations (‘teleworking’). This study explores the extent to which teleworking reduces the need to travel to work and the consequent impacts on economy-wide energy consumption. Methods/Design: The paper provides a systematic review of the current state of knowledge of the energy impacts of teleworking. This includes the energy savings from reduced commuter travel and the indirect impacts on energy consumption associated with changes in non-work travel and home energy consumption. The aim is to identify the conditions under which teleworking leads to a net reduction in economy-wide energy consumption, and the circumstances where benefits may be outweighed by unintended impacts. The paper synthesises the results of 39 empirical studies, identified through a comprehensive search of 9,000 published articles. Review results/Synthesis: Twenty six of the 39 studies suggest that teleworking reduces energy use, and only eight studies suggest that teleworking increases, or has a neutral impact on energy use. However, differences in the methodology, scope and assumptions of the different studies make it difficult to estimate ‘average’ energy savings. The main source of savings is the reduced distance travelled for commuting, potentially with an additional contribution from lower office energy consumption. However, the more rigorous studies that include a wider range of impacts (e.g. non-work travel or home energy use) generally find smaller savings. Discussion: Despite the generally positive verdict on teleworking as an energy-saving practice, there are numerous uncertainties and ambiguities about its actual or potential benefits. These relate to the extent to which teleworking may lead to unpredictable increases in non-work travel and home energy use that may outweigh the gains from reduced work travel. The available evidence suggests that economy-wide energy savings are typically modest, and in many circumstances could be negative or non-existent

Perspectives on care and communication involving incurably ill Turkish and Moroccan patients, relatives and professionals: a systematic literature review

<p>Abstract</p> <p>Background</p> <p>Our aim was to obtain a clearer picture of the relevant care experiences and care perceptions of incurably ill Turkish and Moroccan patients, their relatives and professional care providers, as well as of communication and decision-making patterns at the end of life. The ultimate objective is to improve palliative care for Turkish and Moroccan immigrants in the Netherlands, by taking account of socio-cultural factors in the guidelines for palliative care.</p> <p>Methods</p> <p>A systematic literature review was undertaken. The data sources were seventeen national and international literature databases, four Dutch journals dedicated to palliative care and 37 websites of relevant national and international organizations. All the references found were checked to see whether they met the structured inclusion criteria. Inclusion was limited to publications dealing with primary empirical research on the relationship between socio-cultural factors and the health or care situation of Turkish or Moroccan patients with an oncological or incurable disease. The selection was made by first reading the titles and abstracts and subsequently the full texts. The process of deciding which studies to include was carried out by two reviewers independently. A generic appraisal instrument was applied to assess the methodological quality.</p> <p>Results</p> <p>Fifty-seven studies were found that reported findings for the countries of origin (mainly Turkey) and the immigrant host countries (mainly the Netherlands). The central themes were experiences and perceptions of family care, professional care, end-of-life care and communication. Family care is considered a duty, even when such care becomes a severe burden for the main female family caregiver in particular. Professional hospital care is preferred by many of the patients and relatives because they are looking for a cure and security. End-of-life care is strongly influenced by the continuing hope for recovery. Relatives are often quite influential in end-of-life decisions, such as the decision to withdraw or withhold treatments. The diagnosis, prognosis and end-of-life decisions are seldom discussed with the patient, and communication about pain and mental problems is often limited. Language barriers and the dominance of the family may exacerbate communication problems.</p> <p>Conclusions</p> <p>This review confirms the view that family members of patients with a Turkish or Moroccan background have a central role in care, communication and decision making at the end of life. This, in combination with their continuing hope for the patient’s recovery may inhibit open communication between patients, relatives and professionals as partners in palliative care. This implies that organizations and professionals involved in palliative care should take patients’ socio-cultural characteristics into account and incorporate cultural sensitivity into care standards and care practices<it>.</it></p

Malignancies in Prader-Willi syndrome: results from a large international cohort and literature review

CONTEXT: Prader-Willi syndrome (PWS) is a complex disorder combining hypothalamic dysfunction, neurodevelopmental delay, hypotonia, and hyperphagia with risk of obesity and its complications. PWS is caused by the loss of expression of the PWS critical region, a cluster of paternally expressed genes on chromosome 15q11.2-q13. As life expectancy of patients with PWS increases, age-related diseases like malignancies might pose a new threat to health. OBJECTIVE: To investigate the prevalence and risk factors of malignancies in patients with PWS and to provide clinical recommendations for cancer screening. METHODS: We included 706 patients with PWS (160 children, 546 adults). We retrospectively collected data from medical records on past or current malignancies, the type of malignancy and risk factors for malignancy. Additionally, we searched the literature for information about the relationship between genes on chromosome 15q11.2-q13 and malignancies. RESULTS: Seven adults (age range 18-55 years old) had been diagnosed with a malignancy (acute lymphoblastic leukemia, intracranial hemangiopericytoma, melanoma, stomach adenocarcinoma, biliary cancer, parotid adenocarcinoma and colon cancer). All patients with a malignancy had a paternal 15q11-13 deletion. The literature review showed that several genes on chromosome 15q11.2-q13 are related to malignancies. CONCLUSION: Malignancies are rare in patients with PWS. Therefore, screening for malignancies is only indicated when clinically relevant symptoms are present such as unexplained weight loss, loss of appetite, symptoms suggestive of paraneoplastic syndrome, or localizing symptoms. Given the increased cancer risk associated with obesity, which is common in PWS, participation in national screening programs should be encouraged

Assessing quality of hepato-pancreato-biliary surgery: nationwide benchmarking

Background: Clinical auditing is a powerful tool to evaluate and improve healthcare. Deviations from the expected quality of care are identified by benchmarking the results of individual hospitals using national averages. This study aimed to evaluate the use of quality indicators for benchmarking hepato-pancreato-biliary (HPB) surgery and when outlier hospitals could be identified. Methods: A population-based study used data from two nationwide Dutch HPB audits (DHBA and DPCA) from 2014 to 2021. Sample size calculations determined the threshold (in percentage points) to identify centres as statistical outliers, based on current volume requirements (annual minimum of 20 resections) on a two-year period (2020–2021), covering mortality rate, failure to rescue (FTR), major morbidity rate and textbook/ideal outcome (TO) for minor liver resection (LR), major LR, pancreaticoduodenectomy (PD) and distal pancreatectomy (DP). Results: In total, 10 963 and 7365 patients who underwent liver and pancreatic resection respectively were included. Benchmark and corresponding range of mortality rates were 0.6% (0 −3.2%) and 3.3% (0–16.7%) for minor and major LR, and 2.7% (0–7.0%) and 0.6% (0–4.2%) for PD and DP respectively. FTR rates were 5.4% (0–33.3%), 14.2% (0–100%), 7.5% (1.6%–28.5%) and 3.1% (0–14.9%). For major morbidity rate, corresponding rates were 9.8% (0–20.5%), 28.1% (0–47.1%), 36% (15.8%–58.3%) and 22.3% (5.2%–46.1%). For TO, corresponding rates were 73.6% (61.3%–94.4%), 54.1% (35.3–100), 46.8% (25.3%–59.4%) and 63.3% (30.7%–84.6%). Mortality rate thresholds indicating a significant outlier were 8.6% and 15.4% for minor and major LR and 14.2% and 8.6% for PD and DP. For FTR, these thresholds were 17.9%, 31.6%, 22.9% and 15.0%. For major morbidity rate, these thresholds were 26.1%, 49.7%, 57.9% and 52.9% respectively. For TO, lower thresholds were 52.5%, 32.5%, 25.8% and 41.4% respectively. Higher hospital volumes decrease thresholds to detect outliers. Conclusion: Current event rates and minimum volume requirements per hospital are too low to detect any meaningful between hospital differences in mortality rate and FTR. Major morbidity rate and TO are better candidates to use for benchmarking

Assessing quality of hepato-pancreato-biliary surgery: nationwide benchmarking

Background: Clinical auditing is a powerful tool to evaluate and improve healthcare. Deviations from the expected quality of care are identified by benchmarking the results of individual hospitals using national averages. This study aimed to evaluate the use of quality indicators for benchmarking hepato-pancreato-biliary (HPB) surgery and when outlier hospitals could be identified. Methods: A population-based study used data from two nationwide Dutch HPB audits (DHBA and DPCA) from 2014 to 2021. Sample size calculations determined the threshold (in percentage points) to identify centres as statistical outliers, based on current volume requirements (annual minimum of 20 resections) on a two-year period (2020–2021), covering mortality rate, failure to rescue (FTR), major morbidity rate and textbook/ideal outcome (TO) for minor liver resection (LR), major LR, pancreaticoduodenectomy (PD) and distal pancreatectomy (DP). Results: In total, 10 963 and 7365 patients who underwent liver and pancreatic resection respectively were included. Benchmark and corresponding range of mortality rates were 0.6% (0 −3.2%) and 3.3% (0–16.7%) for minor and major LR, and 2.7% (0–7.0%) and 0.6% (0–4.2%) for PD and DP respectively. FTR rates were 5.4% (0–33.3%), 14.2% (0–100%), 7.5% (1.6%–28.5%) and 3.1% (0–14.9%). For major morbidity rate, corresponding rates were 9.8% (0–20.5%), 28.1% (0–47.1%), 36% (15.8%–58.3%) and 22.3% (5.2%–46.1%). For TO, corresponding rates were 73.6% (61.3%–94.4%), 54.1% (35.3–100), 46.8% (25.3%–59.4%) and 63.3% (30.7%–84.6%). Mortality rate thresholds indicating a significant outlier were 8.6% and 15.4% for minor and major LR and 14.2% and 8.6% for PD and DP. For FTR, these thresholds were 17.9%, 31.6%, 22.9% and 15.0%. For major morbidity rate, these thresholds were 26.1%, 49.7%, 57.9% and 52.9% respectively. For TO, lower thresholds were 52.5%, 32.5%, 25.8% and 41.4% respectively. Higher hospital volumes decrease thresholds to detect outliers. Conclusion: Current event rates and minimum volume requirements per hospital are too low to detect any meaningful between hospital differences in mortality rate and FTR. Major morbidity rate and TO are better candidates to use for benchmarking

Towards Endometriosis Diagnosis by Gadofosveset-Trisodium Enhanced Magnetic Resonance Imaging

Endometriosis is defined as the presence of endometrial tissue outside the uterus. It affects 10–15% of women during reproductive age and has a big personal and social impact due to chronic pelvic pain, subfertility, loss of work-hours and medical costs. Such conditions are exacerbated by the fact that the correct diagnosis is made as late as 8–11 years after symptom presentation. This is due to the lack of a reliable non-invasive diagnostic test and the fact that the reference diagnostic standard is laparoscopy (invasive, expensive and not without risks). High-molecular weight gadofosveset-trisodium is used as contrast agent in Magnetic Resonance Imaging (MRI). Since it extravasates from hyperpermeable vessels more easily than from mature blood vessels, this contrast agent detects angiogenesis efficiently. Endometriosis has high angiogenic activity. Therefore, we have tested the possibility to detect endometriosis non-invasively using Dynamic Contrast-Enhanced MRI (DCE-MRI) and gadofosveset-trisodium as a contrast agent in a mouse model. Endometriotic lesions were surgically induced in nine mice by autologous transplantation. Three weeks after lesion induction, mice were scanned by DCE-MRI. Dynamic image analysis showed that the rates of uptake (inwash), persistence and outwash of the contrast agent were different between endometriosis and control tissues (large blood vessels and back muscle). Due to the extensive angiogenesis in induced lesions, the contrast agent persisted longer in endometriotic than control tissues, thus enhancing the MRI signal intensity. DCE-MRI was repeated five weeks after lesion induction, and contrast enhancement was similar to that observed three weeks after endometriosis induction. The endothelial-cell marker CD31 and the pericyte marker α-smooth-muscle-actin (mature vessels) were detected with immunohistochemistry and confirmed that endometriotic lesions had significantly higher prevalence of new vessels (CD31 only positive) than the uterus and control tissues. The diagnostic value of gadofosveset-trisodium to detect endometriosis should be tested in human settings

NPHP4 Variants Are Associated With Pleiotropic Heart Malformations

Rationale: Congenital heart malformations are a major cause of morbidity and mortality, especially in young children. Failure to establish normal left-right (L-R) asymmetry often results in cardiovascular malformations and other laterality defects of visceral organs. Objective: To identify genetic mutations causing cardiac laterality defects. Methods and Results: We performed a genome-wide linkage analysis in patients with cardiac laterality defects from a consanguineous family. The patients had combinations of defects that included dextrocardia, transposition of great arteries, double-outlet right ventricle, atrioventricular septal defects, and caval vein abnormalities. Sequencing of positional candidate genes identified mutations in NPHP4. We performed mutation analysis of NPHP4 in 146 unrelated patients with similar cardiac laterality defects. Forty-one percent of these patients also had laterality defects of the abdominal organs. We identified 8 additional missense variants that were absent or very rare in control subjects. To study the role of nphp4 in establishing L-R asymmetry, we used antisense morpholinos to knockdown nphp4 expression in zebrafish. Depletion of nphp4 disrupted L-R patterning as well as cardiac and gut laterality. Cardiac laterality defects were partially rescued by human NPHP4 mRNA, whereas mutant NPHP4 containing genetic variants found in patients failed to rescue. We show that nphp4 is involved in the formation of motile cilia in Kupffer's vesicle, which generate asymmetrical fluid flow necessary for normal L-R asymmetry. Conclusions: NPHP4 mutations are associated with cardiac laterality defects and heterotaxy. In zebrafish, nphp4 is essential for the development and function of Kupffer's vesicle cilia and is required for global L-R patterning