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Copyright of Maandblad voor Ondernemingsrecht is the property of Boom uitgevers Den Haag and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: The role of diverting ileostomy is debated in rectal cancer surgery with primary anastomosis. The aim of this study was to evaluate the associated morbidity and hospital costs of diversion after sphincter saving TaTME surgery. Methods: All patients undergoing TaTME with primary anastomosis for rectal cancer between January 2012 and December 2019 in a single centre in the Netherlands were included. Patients with diverting ileostomy creation during primary surgery were compared with those without ileostomy. Outcomes included length of hospital stay, anastomotic leakage rates and total hospital costs at 1 year. Results: One hundred and one patients were included in the ileostomy group, and 46 patients were in the non-ileostomy group. The number of female patients was 31 (30.7%) in the ileostomy group and 21 (45.7%) in the non-ileostomy group Mean age was 64.5 ± 11.1 years in the ileostomy group and 62.6 ± 10.7 years in the non-ileostomy group The anastomotic leakage rate was 21.7% in the non-ileostomy group and 15.8% in the ileostomy group (p = 0.385). The grade of leakage and number of anastomotic takedowns did not differ between groups. Mean costs at 1 year after surgery was €26,500.13 in the ileostomy group and €16,852.61 in the non-ileostomy group. The main cost driver was longer total length of hospital stay at 1 year (mean 12.4 ± 13.3 days vs 20.6 ± 12.6 days, p = 0.000). Conclusions: Morbidity and associated costs after diverting ileostomy are high. The incidence and morbidity of anastomotic leakage was not reduced by creation of an ileostomy. Omission of a diverting ileostomy after TaTME could possibly result in a reduction in treatment associated morbidity and costs. [ABSTRACT FROM AUTHOR]

Targeted cancer therapy with monoclonal antibodies has proven successful for different cancer types but is limited by the availability of suitable antibody targets. CD43s, a unique sialylated form of CD43 expressed by hematologic malignancies, is a recently identified target and antibodies interacting with CD43s may have therapeutic potential against acute myeloid leukemia (AML) and myelodysplastic syndrome. CD43s is recognized by the human antibody AT1413, that was derived from a high-risk AML patient who successfully cleared leukemia after allogeneic stem cell transplantation. Here we observed that AT1413 binds also to certain non-hematopoietic tumor cells, particularly melanoma and breast cancer. AT1413 immune precipitated CD43s from melanoma cells confirming that it recognizes the same target on melanoma as on AML. AT1413 induced antibody-dependent cellular cytotoxicity against short-term cultured patient-derived melanoma samples. However, AT1413 was unable to affect the growth of melanoma cells in vivo. To increase the efficacy of AT1413 as a therapeutic antibody, we generated two different formats of bispecific T-cell engaging antibodies (TCEs): one binding bivalently (bTCE) and the other monovalently (knob-in-hole; KiH) to both CD43s and CD3ε. In vitro, these TCEs redirected T-cell cytotoxicity against melanoma cells with differences in potencies. To investigate their effects in vivo, we grafted mice that harbor a human immune system with the melanoma cell line A375. Treatment with both AT1413 bTCE and AT1413 KiH significantly reduced tumor outgrowth in these mice. These data indicate a broad therapeutic potential of AT1413 that includes AML and CD43s-expressing solid tumors that originate from CD43-negative tissues. [ABSTRACT FROM AUTHOR]

Measurement of intracranial aneurysm wall motion may refine the current rupture risk estimation. A golden standard for measuring aneurysm pulsation is lacking. The aim is to evaluate magnitudes of aneurysm pulsation as published in current literature. Embase and PubMed were searched for publications containing quantitative measures of cardiac-cycle related cerebral aneurysm pulsation (no date or language restrictions). Eleven studies were included, covering 197 unruptured and untreated cerebral aneurysms. Quantitative pulsation measurements were extracted from the studies. Characteristics of the study population and aneurysms were taken into account, as well as the imaging modality, scanning technique and data processing methods used. A meta-analysis was performed of studies with similar methodologies and individual IA measures and locations. The magnitude of the absolute volume pulsations varied between 14 ± 9 mm3 and 106 ± 123 mm3 and the mean relative volume change varied between 5 and 36%. The meta-analysis revealed a positive correlation between size and absolute volume change. The relative volume change in Basilar artery aneurysms seems smaller. No authors were contacted for original study data and articles only describing visual pulsations were excluded. The variation in methodologies impedes an accurate estimation of the magnitude of IA pulsations. Validation of aneurysm pulsation measurement is crucial prior to clinical studies evaluating IA pulsatility in relation to IA rupture risk. Prerequisite is a reliable and robust imaging method with high spatial and temporal resolution and standardization of the image analysis methods. [ABSTRACT FROM AUTHOR]

Copyright of Caribisch Juristenblad is the property of Boom uitgevers Den Haag and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

To obtain a state-of-the-art benchmark potential energy surface (PES) for the archetypal oxidative addition of the methane C-H bond to the palladium atom, we have explored this PES using a hierarchical series of ab initio methods (Hartree-Fock, second-order Møller-Plesset perturbation theory, fourth-order Møller-Plesset perturbation theory with single, double and quadruple excitations, coupled cluster theory with single and double excitations (CCSD), and with triple excitations treated perturbatively [CCSD(T)]) and hybrid density functional theory using the B3LYP functional, in combination with a hierarchical series of ten Gaussian-type basis sets, up to g polarization. Relativistic effects are taken into account either through a relativistic effective core potential for palladium or through a full four-component all-electron approach. Counterpoise corrected relative energies of stationary points are converged to within 0.1–0.2 kcal/mol as a function of the basis-set size. Our best estimate of kinetic and thermodynamic parameters is -8.1 (-8.3) kcal/mol for the formation of the reactant complex, 5.8 (3.1) kcal/mol for the activation energy relative to the separate reactants, and 0.8 (-1.2) kcal/mol for the reaction energy (zero-point vibrational energy-corrected values in parentheses). This agrees well with available experimental data. Our work highlights the importance of sufficient higher angular momentum polarization functions, f and g, for correctly describing metal–d-electron correlation and, thus, for obtaining reliable relative energies. We show that standard basis sets, such as LANL2DZ+1f for palladium, are not sufficiently polarized for this purpose and lead to erroneous CCSD(T) results. B3LYP is associated with smaller basis set superposition errors and shows faster convergence with basis-set size but yields relative energies (in particular, a reaction barrier) that are ca. 3.5 kcal/mol higher than the corresponding CCSD(T) values. © 2004 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Background: Radical gastrectomy is the cornerstone of the treatment of gastric cancer. For tumors invading the pancreas, en-bloc partial pancreatectomy may be needed for a radical resection. The aim of this study was to evaluate the outcome of gastrectomies with partial pancreatectomy for gastric cancer.Methods: Patients who underwent gastrectomy with or without partial pancreatectomy for gastric or gastro-oesophageal junction cancer between 2011 and 2015 were selected from the Dutch Upper GI Cancer Audit (DUCA). Outcomes were resection margin (pR0) and Clavien-Dindo grade ≥ III postoperative complications and survival. The association between partial pancreatectomy and postoperative complications was analyzed with multivariable logistic regression. Overall survival of patients with partial pancreatectomy was estimated using the Kaplan-Meier method.Results: Of 1966 patients that underwent gastrectomy, 55 patients (2.8%) underwent en-bloc partial pancreatectomy. A pR0 resection was achieved in 45 of 55 patients (82% versus 85% in the group without additional resection, P = 0.82). Clavien-Dindo grade ≥ III complications occurred in 21 of 55 patients (38% versus 17%, P < 0.001). Median overall survival [95% confidence interval] was 15 [6.8-23.2] months. For patients with and without perioperative systemic therapy, median survival was 20 [12.3-27.7] and 10 [5.7-14.3] months, and for patients with pR0 and pR1 resection, it was 20 [11.8-28.3] and 5 [2.4-7.6] months, respectively.Conclusions: Gastrectomy with partial pancreatectomy is not only associated with a pR0 resection rate of 82% but also with increased postoperative morbidity. It should only be performed if a pR0 resection is feasible. [ABSTRACT FROM AUTHOR]

Aim: In patients who have undergone a polypectomy of a malignant rectal polyp without histopathological risk factors other than an involved or unclear resection margin, additional local excision is often performed. Evidence to support this approach is lacking. The aim of this systematic review and meta‐analysis was to determine the outcome in terms of local recurrence, disease‐free survival (DFS) and overall survival (OS) of additional local excision following incomplete polypectomy for low risk T1 rectal cancer. Methods: A comprehensive search for published studies was performed. Only studies in which there was incomplete (or ≤ 1 mm) removal of pT1 rectal polyps or in which the resection plane could not be assessed were included. For each included study data on tumour stage, histological factors, surgical technique, local recurrence rate, 5‐year DFS and 5‐year OS were extracted. The PROSPERO registration number is CRD42017062702. Results: A total of 580 studies were retrieved by the search in the MEDLINE database, Embase and the Cochrane Library. After careful appreciation, four studies were included in the analysis, comprising 102 patients of whom the majority had undeterminable (Rx) resection margins. Local excision via transanal endoscopic microsurgery was reported most frequently. Only 1% of patients developed a local recurrence. One study reported 5‐year DFS and 5‐year OS of 96% and 87% respectively. Conclusion: This study supports the use of additional local excision techniques for rectal cancer patients who underwent an incomplete polypectomy for a malignant rectal polyp in the absence of risk factors other than an uncertain resection margin. [ABSTRACT FROM AUTHOR]

Summary: Background: The role of sensitization to commercially available allergens of English walnut (Juglans regia) Jug r 1, 2 and 3 in walnut allergy has been previously investigated in walnut allergic adults and was unable to explain all cases of walnut allergy. Objectives: Identify recognized walnut allergens, other than the ones previously investigated (Jug r 1‐3), in walnut allergic adults and determine the sensitization frequency and diagnostic value. Methods: Three different in‐house walnut extracts were prepared and analysed on SDS‐PAGE blots to identify allergenic walnut proteins. Immunoblots and immunoprecipitation, followed by LC‐MS analysis, were performed to screen for, and confirm, IgE binding to walnut allergens in selected walnut allergic adults. In a cohort of 55 walnut challenged adults, including 33 allergic and 22 tolerant, sensitization to native and recombinant walnut allergen Jug r 4 was assessed using immunoblotting and immuno‐line blot (EUROLINE), respectively. Results: Screening of sera of 8 walnut allergic adults identified Jug r 4 as an allergen in our population. In the total cohort of 55 subjects, 5 were positive for Jug r 4 on immunoblot and 10 on EUROLINE. All but one EUROLINE positive subject had a positive food challenge (sensitivity 27%, specificity 95%, PPV 90%, NPV 47%). All 5 subjects positive on immunoblot were also positive on EUROLINE. LC‐MS analysis showed a lack of Jug r 4 in the ImmunoCAP extract. Co‐sensitization to other 11S albumins (eg hazelnut Cor a 9) was common in Jug r 4 sensitized subjects, potentially due to cross‐reactivity. Conclusions: Walnut 11S globulin Jug r 4 is a relevant minor allergen, recognized by 27% of walnut allergic adults. It has a high positive predictive value of 90% for walnut allergy. Specific IgE against Jug r 4 occurred mostly with concomitant sensitization to other walnut components, mainly Jug r 1. [ABSTRACT FROM AUTHOR]

Objectives: Ischaemic stroke is one of the leading causes of death and disability worldwide. Although the secondary preventive medication should be continued for life, its use commonly declines in time. This may lead to recurrent vascular events. In this study, we investigated if during a long follow‐up period discontinuation of medication (non‐persistence) in real life ischaemic stroke patients increased the risk of recurrent vascular events. Materials and methods: This was a retrospective cohort study with the data retrieved from a database and the original patient records. The occurrence of new vascular events was determined from the electronic medical record. Medication use at time of follow‐up was ascertained using the pharmacy‐link in the electronic medical file and through a telephone interview. Primary endpoint was recurrent vascular events. Patients with two or more vascular risk factors were considered as having a high‐risk profile. Results: A total of 286 patients (persistent n = 182 and non‐persistent n = 104) were included. After median follow‐up period of 5½ years in the persistent group 14.8% had a recurrent vascular event, vs 23.1% in the non‐persistent group (P = .801). In the patients with a high‐risk profile, the persistent group had significantly less recurrent vascular events than the non‐persistent group (23.5% against 46.4% P = .021). Conclusion: After a long follow‐up period, ischaemic stroke patients with a high vascular risk profile who stopped taking their secondary preventive medication had an increased risk of a recurrent vascular events. [ABSTRACT FROM AUTHOR]

In this contribution we present the direct conversion of sodium phosphinate (NaH2PO2 ·H2O) to symmetrical sodium diarylphosphinates and their corresponding acids by using palladium catalysis. This route eliminates the need for chlorinated precursors, such as PCl3 and intermediate alkyl- or ammoniumphosphinates. [ABSTRACT FROM AUTHOR]

Survival during the first year after first calving was investigated over the last 25 years, 1989–2013, as well as how the association of survival with season of calving, age at first calving (AFC) and within-herd production level has changed over that period. The data set contained 1 108 745 Dutch black-and-white cows in 2185 herds. Linear models were used to estimate (1) effect of year and season and their interaction and (2) effect of AFC, within-herd production level, and 5-year intervals and their two-way interactions, and the genetic trend. All models contained AFC and percentage of Holstein Friesian as a fixed effect, and herd-year-season, sire and maternal grandsire as random effects. Survival and functional survival were analysed. Functional survival was defined as survival adjusted for within-herd production level. Survival rate increased by 8% up to 92% in the last 25 years. When accounting for pedigree, survival showed no improvement up to 1999, but improved since then. Genetically, survival increased 3% to 4% but functional survival did not increase over the 25 years. We found an interesting difference between the genetic trends for survival and functional survival for bulls born between 1985 and 1999, where the trend for survival was still increasing, but was negative for functional survival. Since 1999, genetic trend picked up again for both survival and functional survival. AFC, season of calving and within-herd production level affected survival. Survival rate decreased 0.6%/month for survival and 1.5% for functional survival between AFC of 24 and 32 months. Calving in summer resulted in 2.0% higher survival than calving in winter. Within herd, low-producing cows had a lower survival rate than high-producing cows. However, these effects became less important during the recent years. Based on survival optimum AFC is around 24 months, but based on functional survival it is better to have an AFC<24 months. Overall, survival rate of heifers has improved considerably in the past 25 years, initially due to the focus on a high milk production. More recently, the importance of a high milk production has been reduced towards attention for functional survival. [ABSTRACT FROM PUBLISHER]

Background. The Smith-Lemli-Opitz syndrome (SLOS), due to defective function of 7-dehydrocholesterol reductase, is an autosomal recessive disorder that is more common than other defects in cholesterol biosynthesis. The dysmorphology can be suggestive, but biochemical and genetic investigations are required for confirmation of this diagnosis to assist with the management of the patient and planning for future children in affected families. Objective. To perform biochemical and genetic work-ups in four South African families of European ancestry with suspected SLOS in a range of presentations, from early fatality, congenital malformations, feeding problems and developmental delay. Methods. Plasma was analysed by ultraviolet spectrophotometry. The genetic cause was investigated by polymerase chain reaction, followed by high-resolution melting and sequencing of amplicons displaying abnormal patterns. Results. Spectrophotometry confirmed the diagnosis in three families. Genetic confirmation was made in these patients, and carrier status confirmed in the parents of the fatal case. All the patients were of European ancestry, and the mutations reflected those in European studies. Conclusion. This rare disorder should be considered in antenatal assessment when increased nuchal lucency is detected on sonography, or in newborns with syndactyly, hypotonia and feeding problems. Less severe forms could present with developmental delay and behavioural problems. Confirmation of the diagnosis may assist in decisions about nutritional management as well as future pregnancies in the affected family and primary relatives. [ABSTRACT FROM AUTHOR]

generic LC-MS/MS method was developed for the analysis of potentially genotoxic alkyl halides. A broad selection of alkyl halides were derivatized using 4-dimethylaminopyridine in acetonitrile. The reaction conditions for derivatization, i.e., solvent, reaction time, temperature and concentration of alkyl halide, active pharmaceutical ingredient (API), and reagent, were optimized for sensitivity and robustness. The interference of the matrix and the API and the presence of water on the derivatization reaction were investigated for a model drug product (paracetamol/caffeine tablets). Hydrophilic interaction liquid chromatography was used to allow a quantitative determination of the derivatives by tandem mass spectrometry. The derivatization reaction was shown to be selective for alkyl halides, although some reactivity was also observed for an aromatic sulfonate, which is also genotoxic. Even though differences in reaction efficiencies have been observed, the enhanced sensitivity obtained by the derivatization allows the majority of the alkyl halides to be detected by MS/MS at relevant levels for genotoxic impurity evaluation, i.e., 10 mg kg. Another key advantage is that for the majority of derivatives, reagent-related fragments are produced, which allows low-level screening for alkyl halides. Highly specific MS detection can be performed using neutral loss and precursor ion scan experiments. The applicability of a generic screening method will make the genotox evaluation less dependent on the quality of assessments based on predictions only, and it will provide essential information during the development of new chemical entities. In addition to screening, target analysis in the low milligrams per kilogram range can be performed. A similar response of the derivatized compounds was obtained in the range of 1-100 mg kg with a reproducibility better than 10%, which is sufficient for the determination of alkyl halides in APIs and drug products. [ABSTRACT FROM AUTHOR]

Trehalose-6-phosphate (T6P) is an intermediate in the plant metabolic pathway that results in trehalose production. T6P has been shown to inhibit the sucrose nonfermenting-1-related protein kinase 1, which is a major regulator of metabolism. The quantitation of T6P has proven difficult due to the complexity of the plant matrix and the low abundance of T6P in plant tissues. The aim of this work was to develop a quantitation method for T6P present in Arabidopsis tissues, with capillary electrophoresis (CE) coupled to electrospray ionization-mass spectrometry (MS) with a sheath liquid (SL) interface. The CE-MS method was first optimized with respect to T6P signal intensity and separation of isomers by studying the composition of the background electrolyte (BGE) and SL. The use of triethylamine (TEA) in the BGE was favorable, providing separation of T6P from sucrose-6-phosphate and minimizing ionization suppression. Replacing ammonium acetate with TEA enhanced T6P signal intensities more than four times. The optimized method allowed quantification of T6P in plant extracts with good linearity ( r > 0.99) within a biologically relevant concentration range. The limit of quantification was 80 nM in Arabidopsis extracts, corresponding to 33 pmol/g plant fresh weight. The CE-MS method was applied to the determination of T6P in seedlings from wild type (WT) Arabidopsis and mutants lacking the trehalase AtTRE1, tre1-1, challenged with trehalose or sorbitol. T6P accumulation in tre1-1 plants grown on sorbitol was about twice the level of T6P found in WT. CE-MS is shown to be a fast and reliable technique to analyze phosphodisaccharides for seedling extracts. The low sample volume requirement of CE and its direct MS coupling makes it an attractive alternative for anion-exchange liquid chromatography-MS. [ABSTRACT FROM AUTHOR]

In this work, the usefulness of capillary electrophoresis-electrospray ionization time-of-flight-mass spectrometry for the analysis of biopharmaceuticals was studied. Noncovalently bound capillary coatings consisting of Polybrene-poly(vinyl sulfonic acid) or Polybrene-dextran sulfate-Polybrene were used to minimize protein and peptide adsorption, and achieve good separation efficiencies. The potential of the capillary electrophoresis-mass spectrometry (CE-MS) system to characterize degradation products was investigated by analyzing samples of the drugs, recombinant human growth hormone (rhGH) and oxytocin, which had been subjected to prolonged storage, heat exposure, and/or different pH values. Modifications could be assigned based on accurate masses as obtained with time-of-flight-mass spectrometry (TOF-MS) and migration times with respect to the parent compound. For heat-exposed rhGH, oxidations, sulfonate formation, and deamidations were observed. Oxytocin showed strong deamidation (up to 40%) upon heat exposure at low pH, whereas at medium and high pH, mainly dimer (>10%) and trisulfide formation (6-7%) occurred. Recombinant human interferon-β-1a (rhIFN-β) was used to evaluate the capability of the CE-MS method to assess glycan heterogeneity of pharmaceutical proteins. Analysis of this N-glycosylated protein revealed a cluster of resolved peaks which appeared to be caused by at least ten glycoforms differing merely in sialic acid and hexose N-acetylhexosamine composition. Based on the relative peak area (assuming an equimolar response per glycoform), a quantitative profile could be derived with the disialytated biantennary glycoform as most abundant (52%). Such a profile may be useful for in-process and quality control of rhIFN-β batches. It is concluded that the separation power provided by combined capillary electrophoresis and TOF-MS allows discrimination of highly related protein species. [ABSTRACT FROM AUTHOR]

In this article we report and reflect on a study about the problems encountered in the implementation of adult education policies in the Limpopo province of South Africa. We used the model of intergovernmental policy implementation of Van Horn and Van Meter as a theoretical framework. We reflect on this study and link the findings with more recent literature on and experiences with developments in the implementation of adult education policies. The findings of our study show several discontinuities and contradictions in the implementation of an adult education policy, partly caused by the legacies of the past. A central recommendation, informed by contributions from stakeholders at grassroots level, is to use a combination of bottom-up and top-down approaches (bottopdown) in policy development to improve the quality of the implementation. [ABSTRACT FROM AUTHOR]

Background: Radioimmunotherapy (RIT) has been shown to reduce the incidence of local recurrence of colorectal cancer in an experimental model. The aim of the present study was to investigate the survival benefit of RIT compared with chemotherapy. Methods: An anastomosis was constructed in male Wag/Rij rats after intraluminal injection of CC531 tumour cells. The therapeutic efficacy of 177Lu-labelled MG1 (single intravenous dose of 300 MBq/kg, n = 20) was compared with that of 5-fluorouracil-based chemotherapy (6 weekly cycles administered intraperitoneally, n = 20) and no treatment (n = 20). The primary endpoint was survival. Toxicity was monitored by bodyweight measurement. Results: Both chemotherapy and RIT affected bodyweight, but the weight of animals in the RIT group remained significantly higher than in the chemotherapy group (median slope of bodyweight plot 0.48 versus 0.30 g/day; P < 0.001). Kaplan-Meier analysis showed that overall survival in the RIT and chemotherapy groups was significantly better than that in the control group (50 and 46 per cent versus 25 per cent respectively after 170 days; P = 0.024 and P = 0.029). Survival after treatment with RIT did not differ from that after chemotherapy (P = 0.911). Conclusion: RIT is as effective as chemotherapy in experimental colorectal cancer. [ABSTRACT FROM AUTHOR]

A nosocomial outbreak of disease involving 5 patients, 4 of whom died, occurred in South Africa during September-October 2008. The first patient had been transferred from Zambia to South Africa for medical management. Three cases involved secondary spread of infection from the first patient, and 1 was a tertiary infection. A novel arenavirus was identified. The source of the first patient's infection remains undetermined. [ABSTRACT FROM AUTHOR]

Objectives – To determine the proportion of patients with an ischemic stroke that received intravenous (IV) thrombolytic treatment, and reasons why patients are not treated. Methods – A prospective registry of all patients with an ischemic stroke admitted to our emergency department (ED). Results – A total of 286 patients with an ischemic stroke were admitted. Eighty-one patients were admitted within 3 h of onset of neurological deficit, of which 28 received IV thrombolysis. In 25 patients no thrombolytic treatment was given because of the presence of the National Institute of Neurological Disorders and Stroke (NINDS) exclusion criteria, and one patient refused treatment. No thrombolytic treatment was given to 27 patients because of mild neurological deficit or rapid clinical improvement, and after 3 months all these patients were independently living at home without nursing help. Despite a public campaign to gain awareness concerning stroke, the majority of the patients arrived too late at the ED for thrombolytic treatment. Conclusions – A large proportion of the patients with an ischemic stroke are admitted too late to receive IV thrombolysis. More needs to be done to increase both public and medical awareness of stroke as a treatable emergency. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Journal of Chemistry is the property of Canadian Science Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Coordination between care providers of different disciplines is essential to improve the quality of care, in particular for patients with chronic diseases. The way in which general practitioners (GP's) and medical specialists interact has important implications for any healthcare system in which the GP plays the role of gatekeeper to specialist care. Patient experiences and preferences have proven to be increasingly important in discussing healthcare policy. The Dutch government initiated the development of a special website with information for patients on performance indicators of hospitals as well as information on illness or treatment. In the present study we focus on the transition of care at the primary -- secondary interface with reference to the impact of patients' ability to make choices about their secondary care providers. The purpose of this study is to (a) explore experiences and preferences of patients regarding the transition between primary and secondary care, (b) study informational resources on illness/ treatment desired by patients and (c) determine how information supplied could make it easier for the patient to choose between different options for care (hospital or specialist). Methods: We conducted a qualitative study using semi-structured focus group interviews among 71 patients referred for various indications in the north and west of The Netherlands. Results: Patients find it important that they do not have to wait, that they are taken seriously, and receive adequate and individually relevant information. A lack of continuity from secondary to primary care was experienced. The patient's desire for free choice of type of care did not arise in any of the focus groups. Conclusion: Hospital discharge information needs to be improved. The interval between discharge from specialist care and the report of the specialist to the GP might be a suitable performance indicator in healthcare. Patients want to receive information, tailored to their own situation. The need for information, however, is quite variable. Patients do not feel strongly about self-chosen healthcare, contrary to what administrators presently believe. [ABSTRACT FROM AUTHOR]

Background and purpose: Patient outcome is often used as an indicator of quality of hospital care. The aim of this study is to investigate whether there is a straightforward relationship between quality of care and outcome, and whether outcome measures could be used to assess quality of care after stroke. Methods: In 10 centres in The Netherlands, 579 patients with acute stroke were prospectively and consecutively enrolled. Poor outcome was defined as a score on the modified Rankin scale ~3 at 1 year. Quality of care was assessed by relating diagnostic, therapeutic and preventive procedures to indication. Multiple logistic regression models were used to compare observed proportions of patients with poor outcome with expected proportions, after adjustment for patient characteristics and quality of care parameters. Results: A total of 271 (47%) patients were dead or disabled at 1 year. Poor outcome varied across the centres from 29% to 78%. Large differences between centres were also observed in clinical characteristics, prognostic factors and quality of care. For example, between hospital quartiles based on outcome, age ~70 years varied from 50% to 65%, presence of vascular risk factors from 88% to 96%, intravenous fluids when indicated from 35% to 81%, and antihypertensive therapy when indicated from 60% to 85%. The largest part of variation in patient outcome between centres was explained by differences in patient characteristics (Akaike's Information Criterion (AIC) = 134.0). Quality of care parameters explained a small part of the variation in patient outcome )AIC = 5.5). Conclusions: Patient outcome after stroke varies largely between centres and is, for a substantial part, explained by differences in patient characteristics at time of hospital admission. QnIy a small part of the hospital variation in patient outcome is related to differences in quality of care. Unadjusted proportions of poor outcome after stroke are not valid as indicators of quality of care. [ABSTRACT FROM AUTHOR]

A study was initiated to construct a micro-reactor for protein digestion based on trypsin-coated fused-silica capillaries. Initially, surface plasmon resonance was used both for optimization of the surface chemistry applied in the preparation and for monitoring the amount of enzyme that was immobilized. The highest amount of trypsin was immobilized on dextran-coated SPR surfaces which allowed the covalent coupling of 11 ng mm−2 trypsin. Fused-silica capillaries were modified in a similar manner and the resulting open-tubular trypsin-reactors having a pH optimum of pH 8.5, display a high activity when operated at 37 °C and are stable for at least two weeks when used continuously. Trypsin auto-digestion fragments, sample carry-over, and loss of signal due to adsorption of the protein were not observed. On-line digestion without prior protein denaturation, followed by micro-LC separation and photodiode array detection, was tested with horse-heart cytochrome C and horse skeletal-muscle myoglobin. The complete digestion of 20 pmol μL−1 horse cytochrome C was observed when the average residence time of the protein sample in a 140 cm ×50 μm capillary immobilized enzyme reactor (IMER) was 165 s. Mass spectrometric identification of the injected protein on the basis of the tryptic peptides proved possible. Protein digestion was favorable with respect to reaction time and fragments formed when compared with other on-line and off-line procedures. These results and the easy preparation of this micro-reactor provide possibilities for miniaturized enzyme-reactors for on-line peptide mapping and inhibitor screening. [ABSTRACT FROM AUTHOR]

The current clinical diagnosis of Von Hippel-Lindau (VHL) disease demands at least one specific a sporadic VHL manifestation in a patient with familial VHL disease, or, in asporadic patient, at least two or more hemangioblastomas or a single hemangioblastoma in combination with a typical visceral lesion. To evaluate this definition, we studied the frequency of germline VHL mutation in three patients groups: (i) multi-organ involvement (classic VHL), (ii) limited VHL manifestations meeting criteria (non-classic VHL) and (iii) patients with VHL-associated tumors not meeting current diagnostic VHL criteria. In addition, we validated multiplex ligation-dependent probe amplification (MLPA) as a rapid and reliable quantitative method for the identification of germline VHL deletions. The frequency of germline VHL mutations was very high in classic VHL cases with multi-organ involvement (95%), lower in non-classic cases that meet current diagnostic criteria but have limited VHL manifestations or single-organ involvement (24%) and low (3.3%), but tangible in cases not meeting current diagnostic VHL criteria. The detection of germline VHL mutations in patients or families with limited VHL manifestations, or single-organ involvement is relevant for follow-up of probands and early identification of at-risk relatives. [ABSTRACT FROM AUTHOR]

Optimisation of peak capacity is an important strategy in gradient liquid chromatography (LC). This can be achieved by using either long columns or columns packed with small particles. Monolithic columns allow the use of long columns at relatively low back-pressure. The gain in peak capacity using long columns was evaluated by the separation of a tryptic bovine serum albumin digest with an LC–UV–mass spectrometry (MS) system and monolithic columns of different length (150 and 750 mm). Peak capacities were determined from UV chromatograms and MS/MS data were used for Mascot database searching. Analyses with a similar gradient slope for the two columns produced ratios of the peak capacities that were close to the expected value of the square root of the column length ratio. Peak capacities of the short column were 12.6 and 25.0 with 3 and 15 min gradients, respectively, and 29.7 and 41.0 for the long column with 15 and 75 min gradients, respectively. Protein identification scores were also higher for the long column, 641 and 750 for the 3- and 15-min gradients with the short column and 1,376 and 993 for the 15- and 75-min gradients with the long column. Thus, the use of long monolithic columns provides improved peptide separation and increased reliability of protein identification. [ABSTRACT FROM AUTHOR]

Carrion insect succession studies have historically used repeated sampling of single or a few carcasses to produce data, either weighing the carcasses, removing a qualitative subsample of the fauna present, or both, on every visit over the course of decomposition and succession. This study, conducted in a set of related experimental hypotheses with two trials in a single season, investigated the effect that repeated sampling has on insect succession, determined by the number of taxa collected on each visit and by community composition. Each trial lasted at least 21 days, with daily visits on the first 14 days. Rat carcasses used in this study were all placed in the field on the same day, but then either sampled qualitatively on every visit (similar to most succession studies) or ignored until a given day of succession, when they were sampled qualitatively (a subsample) and then destructively sampled in their entirety. Carcasses sampled on every visit were in two groups: those from which only a sample of the fauna was taken and those from which a sample of fauna was taken and the carcass was weighed for biomass determination. Of the carcasses visited only once, the number of taxa in subsamples was compared to the actual number of taxa present when the carcass was destructively sampled to determine if the subsamples adequately represented the total carcass fauna. Data from the qualitative subsamples of those carcasses visited only once were also compared to data collected from carcasses that were sampled on every visit to investigate the effect of the repeated sampling. A total of 39 taxa were collected from carcasses during the study and the component taxa are discussed individually in relation to their role in succession. Number of taxa differed on only one visit between the qualitative subsamples and the actual number of taxa present, primarily because the organisms missed by the qualitative sampling were cryptic (hidden deep within body cavities) or rare (only represented by very few specimens). There were no differences discovered between number of taxa in qualitative subsamples from carcasses sampled repeatedly (with or without biomass determinations) and those sampled only a single time. Community composition differed considerably in later stages of decomposition, with disparate communities due primarily to small numbers of rare taxa. These results indicate that the methods used historically for community composition determination in experimental forensic entomology are generally adequate. [ABSTRACT FROM AUTHOR]

There is little knowledge about the factors that determine the allergenicity of food proteins. One aspect that remains to be elucidated is the effect of the food matrix on immune responses to food proteins. To study the intrinsic immunogenicity of allergens and the influence of the food matrix, purified peanut allergens (Ara h 1, Ara h 2, Ara h 3, or Ara h 6) and a whole peanut extract (PE) were tested in the popliteal lymph node assay (PLNA) and in an oral model of peanut hypersensitivity. In the PLNA, peanut proteins were injected into the hind footpad of BALB/c mice; in the oral exposure experiments C3H/HeOuJ mice were gavaged weekly with PE or allergens in the presence of cholera toxin (CT). Upon footpad injection, none of the allergens induced significant immune activation. In contrast, PE induced an increase in cell number, cytokine production, and activation of antigen-presenting cells. Furthermore, the presence of a food matrix enhanced the immune response to the individual allergens. Oral exposure to the purified allergens in the presence of CT induced specific IgE responses, irrespective of the presence of a food matrix. These results suggest that purified peanut allergens possess little intrinsic immune-stimulating capacity in contrast to a whole PE. Moreover, the data indicate that the food matrix can influence responses to individual proteins and, therefore, the food matrix must be taken into account when developing models for allergenic potential assessment. [ABSTRACT FROM AUTHOR]

We have computed a state-of-the-art benchmark potential energy surface (PES) for the archetypal oxidative addition of the ethane C&bond;C bond to the palladium atom and have used this to evaluate the performance of 24 popular density functionals, covering LDA, GGA, meta-GGA, and hybrid density functionals, for describing this reaction. The ab initio benchmark is obtained by exploring the PES using a hierarchical series of ab initio methods [HF, MP2, CCSD, CCSD(T)] in combination with a hierarchical series of five Gaussian-type basis sets, up to g polarization. Relativistic effects are taken into account either through a relativistic effective core potential for palladium or through a full four-component all-electron approach. Our best estimate of kinetic and thermodynamic parameters is -10.8 (-11.3) kcal/mol for the formation of the reactant complex, 19.4 (17.1) kcal/mol for the activation energy relative to the separate reactants, and -4.5 (-6.8) kcal/mol for the reaction energy (zero-point vibrational energy-corrected values in parentheses). Our work highlights the importance of sufficient higher angular momentum polarization functions for correctly describing metal-d-electron correlation. Best overall agreement with our ab initio benchmark is obtained by functionals from all three categories, GGA, meta-GGA, and hybrid DFT, with mean absolute errors of 1.5 to 2.5 kcal/mol and errors in activation energies ranging from -0.2 to -3.2 kcal/mol. Interestingly, the well-known BLYP functional compares very reasonably with a slight underestimation of the overall barrier by -0.9 kcal/mol. For comparison, with B3LYP we arrive at an overestimation of the overall barrier by 5.8 kcal/mol. On the other hand, B3LYP performs excellently for the central barrier (i.e., relative to the reactant complex) which it underestimates by only -0.1 kcal/mol. © 2005 Wiley Periodicals, Inc. J Comput Chem 26: 1006–1020, 2005 [ABSTRACT FROM AUTHOR]

IgE-binding peanut proteins smaller than 15 kDa were previously identified as potential allergens in the majority of our peanut allergic population.To characterize the novel allergen in order to determine whether it was similar to one of the thus far identified recombinant peanut allergens (Ara h 1–7).An IgE-binding protein of<15 kDa was purified and identified via N-terminal sequencing. Its IgE-binding properties were investigated using immunoblotting, basophil degranulation, and skin prick testing. Possible cross-reacting epitopes with other peanut allergens were studied using IgE-immunoblotting inhibition.The purified protein is a monomeric protein with a molecular weight of 14 981 Da as determined using matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectroscopy. The amino acid sequence of the first 39 N-terminal residues is identical to that of Ara h 6, indicating that the allergen is Ara h 6. It is recognized by 20 out of 29 peanut-allergic patients on IgE-immunoblot, and its potent biological functionality is demonstrated by the degranulation of basophils, even at concentrations below 10 pg/mL, and by positive skin prick reactions. Ara h 6 has homology to Ara h 2, especially in the middle part and at the C-terminal part of the protein. Almost complete inhibition of IgE–Ara h 6 interaction with Ara h 2 demonstrates that at least part of the epitopes of Ara h 6 are cross-reactive with epitopes on Ara h 2.Peanut-derived Ara h 6 is a biologically active allergen recognized by the majority of our peanut-allergic patient population and can be considered a clinically relevant peanut allergen. [ABSTRACT FROM AUTHOR]

Individuals of all vertebrate species differ consistently in their reactions to mildly stressful challenges. These typical reactions, described as personalities or coping strategies, have a clear genetic basis, but the structure of their inheritance in natural populations is almost unknown. We carried out a quantitative genetic analysis of two personality traits (exploration and boldness) and the combination of these two traits (early exploratory behaviour). This study was carried out on the lines resulting from a two-directional artificial selection experiment on early exploratory behaviour (EEB) of great tits (Parus major) originating from a wild population. In analyses using the original lines, reciprocal F1 and reciprocal first backcross generations, additive, dominance, maternal effects ands sex-dependent expression of exploration, boldness and EEB were estimated. Both additive and dominant genetic effects were important determinants of phenotypic variation in exploratory behaviour and boldness. However, no sex-dependent expression was observed in either of these personality traits. These results are discussed with respect to the maintenance of genetic variation in personality traits, and the expected genetic structure of other behavioural and life history traits in general.Heredity (2004) 93, 496-503. doi:10.1038/sj.hdy.6800530 Published online 28 July 2004 [ABSTRACT FROM AUTHOR]

When one member of a couple develops a serious illness, the lives of both partners are likely to be affected. Interventions directed at both partners are generally lacking, however. In the present study, a brief counseling program directed at couples confronted with cancer was evaluated. The intervention focused mainly on the exchange of social support and help between both partners and was aimed at restoring perceptions of equity. Couples were randomly assigned to an experimental group or a waiting-list group. After the intervention, both patients and their partners reported lower levels of perceptions of underinvestment and overbenefit, and higher levels of relationship quality. Moreover, among patients psychological distress decreased after the intervention. These effects were generally maintained until follow-up three months later. Associations between perceptions of equity and relationship quality and psychological distress were also examined. Copyright © 2003 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Geographical variation in Drosophila melanogaster body size is a long-standing problem of life-history evolution. Adaptation to a cold climate invariably produces large individuals, whereas evolution in tropical regions result in small individuals. The proximate mechanism was suggested to involve thermal evolution of resource processing by the developing larvae. In this study an attempt is made to merge proximate explanations, featuring temperature sensitivity of larval resource processing, and ultimate approaches focusing on adult and pre-adult life-history traits. To address the issue of temperature dependent resource allocation to adult size vs. larval survival, feeding was stopped at several stages during the larval development. Under these conditions of food deprivation, two temperate and two tropical populations reared at high and low temperatures produced different adult body sizes coinciding with different probabilities to reach the adult stage. In all cases a phenotypic trade-off between larval survival and adult size was observed. However, the underlying pattern of larval resource allocation differed between the geographical populations. In the temperate populations larval age but not weight predicted survival. Temperate larvae did not invest accumulated resources in survival, instead they preserved larval biomass to benefit adult weight. In other words, larvae from temperate populations failed to re-allocate accumulated resources to facilitate their survival. A low percentage of the larvae survived to adulthood but produced relatively large flies. Conversely, in tropical populations larval weight but not age determined the probability to reach adulthood. Tropical larvae did not invest in adult size, but facilitated their own survival. Most larvae succeeded in pupating but then produced small adults. The underlying physiological mechanism seemed to be an evolved difference in the accessibility of glycogen reserves as a result of thermal adaptation. At low rearing temperatures and in the temperate populations, glycogen levels tended to correlate positively with adult size but negatively with pupation probability. The data presented here offer an explanation of geographical variation in body size by showing that thermal evolution of resource allocation, specifically the ability to access glycogen storage, is the proximate mechanism responsible for the life-history trade-off between larval survival and adult size. [ABSTRACT FROM AUTHOR]

Leukemia in a hydropic fetus with hepatosplenomegaly and Down syndrome was diagnosed at 25 weeks' gestation. Spontaneous demise occurred 10 days after the cordocentesis. A review of the literature of the seven cases described antenatally and 10 cases described in the immediate neonatal period or on examination of the stillborn baby is presented. [ABSTRACT FROM AUTHOR]