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Background: Whether animal exposure and specifically the timing of such exposure alters multiple sclerosis (MS) risk is unclear. We examined whether animal exposure was associated with MS risk, and whether risk differed by the participants age.Methods: We conducted a case-control study within the Nurses' Health Study ((NHS)/NHSII cohorts). Overall, 151 women with MS and 235 controls, matched by age and study cohort, completed an animal exposure history questionnaire. Animal exposure pre-MS onset was assessed as 'any' exposure, then by the participants age, and animal family. Conditional logistic regression was used to estimate relative MS risks, adjusted (adj.RR) for potential confounders.Results: 'Any' animal exposure was reported by 136 (90.1%) MS cases compared to 200 (85.1%) matched controls, with dog exposure being the most common [120 (79.5%) cases vs. 170 (72.3%) controls]. There was no association between 'any' animal exposure and MS risk (adj.RR:1.52;95%CI:0.76-3.04). However, both 'any' animal and specifically dog exposure at ages 10-14 years were associated with an increased MS risk (adj.RR:1.67;95%CI:1.05-2.66 and 1.76;95%CI:1.12-2.78, respectively).Conclusion: Animal exposure, and specifically dog exposure, in early adolescence was associated with an increased risk of MS. Further work is needed to confirm this finding.

The aerobic thermoalkaliphile Caldalkalibacillus thermarum strain TA2.A1 is a member of a separate order of alkaliphilic bacteria closely related to the Bacillales order. Efforts to relate the genomic information of this evolutionary ancient organism to environmental adaptation have been thwarted by the inability to construct a complete genome. The existing draft genome is highly fragmented due to repetitive regions, and gaps between and over repetitive regions were unbridgeable. To address this, Oxford Nanopore Technology’s MinION allowed us to span these repeats through long reads, with over 6000-fold coverage. This resulted in a single 3.34 Mb circular chromosome. The profile of transporters and central metabolism gives insight into why the organism prefers glutamate over sucrose as carbon source. We propose that the deamination of glutamate allows alkalization of the immediate environment, an excellent example of how an extremophile modulates environmental conditions to suit its own requirements. Curiously, plant-like hallmark electron transfer enzymes and transporters are found throughout the genome, such as a cytochrome b6c1 complex and a CO2-concentrating transporter. In addition, multiple self-splicing group II intron-encoded proteins closely aligning to those of a telomerase reverse transcriptase in Arabidopsis thaliana were revealed. Collectively, these features suggest an evolutionary relationship to plant life.

Background: Due to complex processes of implementation of innovations aimed at persons with intellectual disabilities in healthcare organizations, lifestyle interventions are not used as intended or not used at all. In order to provide insight into determinants influencing this implementation, this study aims to ascertain if the Measurement Instrument for Determinants of Innovations (MIDI) is useful for objectively evaluating implementation. Method: With semi-structured interviews, data concerning determinants of implementation of lifestyle interventions were aggregated. These data were compared to the determinants questioned in the MIDI. Adaptations to the MIDI were made in consultation with the author of the MIDI. Results: All determinants of the MIDI, except for that concerning legislation and regulations, were represented in the interview data. Determinants not represented in the MIDI were the level of intellectual disabilities, suitability of materials and physical environment, multi-levelness of interventions and several persons who could be involved in the intervention, such as direct support persons (DSPs), a therapist or family, and the communication between these involved persons. Conclusion: The present authors suggested making adjustments to existing questions of the MIDI in order to improve usability for deployment in organizations that provide care to persons with intellectual disabilities. The adjustments need to be tested with other interventions.

Summary This paper offers a narratological close reading of one of Herodotus’ most celebrated stories. Special attention is paid to the recurrent Herodotean themes and story-patterns which shape it and thus can help to interpret it. For once the advice of a warner is heeded, but the return of the ring shows that Polycrates’ fate is already sealed and cannot be averted anymore. His great good fortune has brought Polycrates the envy of the gods, a concept which must be looked at in terms of the contemporary Ionian interest in ‘balance’ (of the bodily humours, of climate, of good fortune): the gods watch over the balance of the kosmos and when mortals threaten to disturb it (because of excessive power, riches or good fortune), these mortals are brought down. Most of the times these ‘excessive’ mortals also ‘earn’ their fate by committing crimes or making grave mistakes, and the quick account of Polycrates’ earlier career showed him killing one of his brothers and abusing the unwritten law of ξεινίη. When he faithfully executes Amasis’ advice and throws away his precious ring it is already too late and, as Amasis concludes, his fate cannot be changed anymore.

Meat consumption-associated cancer risks relating to the preservative nitrate are receiving considerable attention. Consequently, innovative meat products are being developed with no or reduced nitrate levels. For example, phytochemicals are currently under investigation for their potential to replace nitrate in meat. Consumers are becoming more aware of health aspects of consumed foods, a trend which is accompanied by an increase in health claims on food products. However, consumer acceptance of a health claim is dependent on consumer credibility of the claim. In order to produce a health claim, perceived credible by consumers, it should be known which factors influence consumer credibility. This pilot study investigated the extent to which consumers perceive health claims on innovative meat products credible and which factors influence this credibility. By means of a questionnaire distributed amongst 1010 Dutch participants representative of the Dutch population, factors like health claim promoters, media platforms, and the phrasing of the proposed health claim were investigated. Main results are that the majority of consumers indicates meat products with phytochemicals as acceptable. Promotion by a national health foundation is perceived as credible, and health magazines are perceived as a credible media platform. This study found that neither weekly meat consumption, sex, nor age have effect on the consumer credibility of certain health claims, but that educational level does.

Background Benefits of selective serotonin reuptake inhibitors (SSRIs) in modifying the multiple sclerosis (MS) disease course have been suggested, but their ability to delay disability progression remains unknown. We examined the association between SSRI exposure and MS disability progression. Methods A nested case-control study was conducted using the British Columbia (Canada) Multiple Sclerosis clinical data linked to health administrative data. The primary outcome was a sustained score of 6 (requires a cane to walk) on the Expanded Disability Status Scale (EDSS), and the secondary outcome was the onset of secondary progressive MS (SPMS, an advanced stage of MS). The cases were those who reached a study outcome and were matched with up to four randomly selected controls by sex, age, EDSS and calendar year at study entry using incidence density sampling. The associations between disability worsening and SSRI exposure were assessed with conditional logistic regression models, adjusted for confounders. Results A total of 3920 patients were included in the main analyses, of which 272 reached sustained EDSS 6 and 187 reached SPMS. SSRI exposure was significantly different between patients who reached sustained EDSS 6 and controls [adjusted odds ratio (adjOR):1.44; 95% confidence interval (CI):1.03-2.01]. However, SSRI exposure was not significantly different between those who reached SPMS and their controls (adjOR:1.35; 95%CI:0.89-2.04). Conclusion We found no evidence to suggest that SSRI exposure was associated with a delay in MS disability accumulation or progression. Copyright © 2016 John Wiley & Sons, Ltd.

The alphaproteobacterial general stress response is governed by a conserved partner-switching mechanism that is triggered by phosphorylation of the response regulator PhyR. In the model organism Caulobacter crescentus, PhyR was proposed to be phosphorylated by the histidine kinase PhyK, but biochemical evidence in support of such a role of PhyK is missing. Here, we identify a single-domain response regulator, MrrA, that is essential for general stress response activation in C. crescentus. We demonstrate that PhyK does not function as a kinase but accepts phosphoryl groups from MrrA and passes them on to PhyR, adopting the role of a histidine phosphotransferase. MrrA is phosphorylated by at least six histidine kinases that likely serve as stress sensors. MrrA also transfers phosphate to LovK, a histidine kinase involved in C. crescentus holdfast production and attachment, which also negatively regulates the general stress response. We show that LovK together with the response regulator LovR acts as a phosphate sink to redirect phosphate flux away from the PhyKR branch. In agreement with the biochemical data, an mrrA mutant is unable to activate the general stress response and shows a hyperattachment phenotype, which is linked to decreased expression of the major holdfast inhibitory protein HfiA. We propose that MrrA serves as a central phosphorylation hub that coordinates the general stress response with C. crescentus development and other adaptive behaviors. The characteristic bow-tie architecture of this phosphorylation network with MrrA as the central knot may expedite the evolvability and species-specific niche adaptation of this group of bacteria., IMPORTANCE Two-component systems (TCSs) consisting of a histidine kinase and a cognate response regulator are predominant signal transduction systems in bacteria. To avoid cross talk, TCSs are generally thought to be highly insulated from each other. However, this notion is based largely on studies of the HisKA subfamily of histidine kinases, while little information is available for the HWE and HisKA2 subfamilies. The latter have been implicated in the alphaproteobacterial general stress response. Here, we show that in the model organism Caulobacter crescentus an atypical FATGUY-type single-domain response regulator, MrrA, is highly promiscuous in accepting and transferring phosphoryl groups from and to multiple up- and downstream kinases, challenging the current view of strictly insulated TCSs. Instead, we propose that FATGUY response regulators have evolved in alphaproteobacteria as central phosphorylation hubs to broadly sample information and distribute phosphoryl groups between the general stress response pathway and other TCSs, thereby coordinating multiple cellular behaviors.

The alpha-proteobacterial general stress response is governed by a conserved partner-switching mechanism that is triggered by phosphorylation of the response regulator PhyR. In the model organismCaulobacter crescentusPhyR was proposed to be phosphorylated by the histidine kinase PhyK, but biochemical evidence in support of such a role of PhyK is missing. Here, we identify a single-domain response regulator, MrrA, that is essential for general stress response activation inC. crescentus. We demonstrate that PhyK does not function as a kinase but accepts phosphoryl groups from MrrA and passes them on to PhyR, thereby adopting the role of a histidine phosphotransferase. MrrA is phosphorylated by at least six histidine kinases that likely serve as stress sensors. MrrA also transfers phosphate to LovK, a histidine kinase involved inC. crescentusholdfast production and attachment, that also negatively regulates the general stress response. We show that LovK together with the response regulator LovR acts as a phosphate sink to redirect phosphate flux away from the PhyKR branch. In agreement with the biochemical data, amrrAmutant is unable to activate the general stress response and shows a hyper-attachment phenotype, which is linked to decreased expression of the major holdfast inhibitory protein HfiA. We propose that MrrA serves as a central phosphorylation hub that coordinates the general stress response withC. crescentusdevelopment and other adaptive behaviors. The characteristic bow-tie architecture of this phosphorylation network with MrrA as the central knot may expedite the evolvability and species-specific niche adaptation of this group of bacteria.ImportanceTwo-component systems (TCSs) consisting of a histidine kinase and a cognate response regulator are predominant signal transduction systems in bacteria. To avoid cross-talk, TCS are generally thought to be highly insulated from each other. However, this notion is based largely on studies of the HisKA subfamily of histidine kinases, while little information is available for the HWE and HisKA2 subfamilies. The latter have been implicated in the alpha-proteobacterial general stress response. Here, we show that in the model organismCaulobacter crescentusan atypical FATGUY-type single-domain response regulator (SDRR), MrrA, is highly promiscuous both in accepting and transferring phosphoryl groups from and to a number of up- and downstream kinases, challenging the current view of strictly insulated TCSs. Instead, we propose that FATGUY response regulators have evolved in alpha-proteobacteria to serve as central phosphorylation hubs to broadly sample information and distribute phosphoryl groups between the general stress response pathway and other TCSs, thereby coordinating multiple cellular behaviors. This signaling cascade includes presumable histidine kinases harboring intact catalytic and ATP-binding (CA) domains that, however, do not function as kinases, but instead have adopted a role as histidine phosphotransferases. Our work highlights a complex phosphorylation network in alpha-proteobacteria that coordinates the general stress response with changes in other cellular behaviors and development.

We examined the association between statin use and the risk of rheumatoid arthritis (RA), with special focus on describing the patterns of risks of RA during statin exposure in a large population-based cohort in the United Kingdom. In the Clinical Practice Research Datalink, patients aged ≥40 years with at least one prescription of statins (1995–2009) were selected, and matched by age (+/-5 years), sex, practice and date of first prescription of statins to non-users. The follow-up period of statin use was divided into periods of current, recent and past exposure, with patients moving between these three exposure categories over time. Time-dependent Cox models were used to derive hazard ratios (HRs) of RA, adjusted for disease history and previous drug use. The study population included 1,023,240 patients, of whom 511,620 were statin users. No associations were found between RA and current (HRadj,1.06;99%CI:0.88–1.27) or past statin users (HRadj,1.18;99%CI:0.88–1.57). However, in patients who currently used statins, hazard rates were increased shortly after the first prescription of statins and then gradually decreased to baseline level. The risk of developing RA was increased in recent statin users, as compared to non-users (HRadj,1.39;99% CI:1.01–1.90). The risk of RA is substantially increased in the first year after the start of statins and then diminishes to baseline level. These findings may suggest that statins might accelerate disease onset in patients susceptible to develop RA, but in other patients, statins are probably safe and well tolerated, even after prolonged use. Alternatively, we cannot rule out that confounding by cardiovascular risk factors and ascertainment bias may have influenced the findings.

Objectives To examine the association between the use of statins and the risk of systemic lupus erythematosus (SLE) with focus on describing the patterns of risks over time.Setting A population-based cohort study using the UK Clinical Practice Research Datalink.Participants All patients aged 40 years or older who had at least one prescription of statins during the period 1995-2009 were selected and matched by age, sex, practice and date of first prescription to non-users. The follow-up period of statin users was divided into periods of current, recent and past exposure, with patients moving among these three exposure categories over time. Current statin users were also stratified into 1 year of use.Main outcome measures Time-dependent Cox models were used to calculate HRs of SLE, adjusted for disease history and previous drug exposure.Results We included 1 039 694 patients, of whom 519 847 were statin users. Current statin users did not have an increased risk of developing SLE among patients aged >= 40 years (HRadjusted 0.75, 95% CI 0.53 to 1.07). Current statin users who continued the therapy for >1 year had a 38% lower risk of developing SLE (HRadjusted 0.62, 95% CI 0.42 to 0.93). When more specific definitions for SLE were used, this latter finding, however, was not observed.Conclusions Our findings showed no effect of statins on the risk of developing SLE among patients aged >= 40 years. Further research is needed to study the long-term effects of statins on SLE.

Objective:To examine the association between interferon-β (IFN-β) and potential adverse events using population-based health administrative data in British Columbia, Canada.Methods:Patients with relapsing-remitting multiple sclerosis (RRMS) who were registered at a British Columbia Multiple Sclerosis Clinic (1995–2004) were eligible for inclusion and were followed up until death, absence from British Columbia, exposure to a non–IFN-β disease-modifying drug, or December 31, 2008. Incidence rates were estimated for each potential adverse event (selected a priori and defined with ICD-9/10 diagnosis codes from physician and hospital claims). A nested case-control study was conducted to assess the odds of previous IFN-β exposure for each potential adverse event with at least 30 cases. Cases were matched by age (±5 years), sex, and year of cohort entry, with up to 20 randomly selected (by incidence density sampling) controls. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were estimated with conditional logistic regression adjusted for age at cohort entry.Results:Of the 2,485 eligible patients, 77.9% were women, and 1,031 were treated with IFN-β during follow-up. From the incidence analyses, 27 of the 47 potential adverse events had at least 30 cases. Patients with incident stroke (ORadj 1.83, 95% CI 1.16–2.89), migraine (ORadj 1.55, 95% CI 1.18–2.04), depression (ORadj 1.33, 95% CI 1.13–1.56), and hematologic abnormalities (ORadj 1.32, 95% CI 1.01–1.72) were more likely to have previous exposure to IFN-β than controls.Conclusions:Among patients with RRMS, IFN-β was associated with a 1.8- and 1.6-fold increase in the risk of stroke and migraine and 1.3-fold increases in depression and hematologic abnormalities.

Background: Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) have anti-inflammatory and immuno-modulating properties which are effective in the treatment of cardiovascular disease and in suppressing the symptoms of ongoing autoimmunity. On the other hand, these anti-inflammatory and immuno-modulating effects may facilitate the development of autoimmunity potentially resulting in autoimmune diseases such as rheumatic diseases. Objectives: To determine whether ACE inhibitors and ARBs use was associated with an increased risk of incident rheumatoid arthritis (RA). Methods: A matched case-control study was conducted among antihypertensive patients using the Netherlands Information Network of General Practice (LINH) database from 2001 through 2006. Cases were patients over 40 years of age with a first-time diagnosis of RA. Each case was matched to up to five controls for age, sex, and index date which was selected one year before the first diagnosis of RA. ACE inhibitors and ARBs exposure was considered to be any prescription issued in the period before index date. Logistic regression analysis was used to estimate odds ratios (ORs) and their 95% confidence intervals (CI). Results: Our study included 211 cases and 667 matched controls. After controlling for potential confounders, users of ACE inhibitors or ARBs had adjusted ORs of 1.10 (95% CI: 0.77–1.57) and 1.06 (0.74–1.53), respectively. The adjusted ORs of incident RA among current and past users of ACE inhibitors were 1.14 (0.73–1.77) and 0.60 (0.27–1.30). Current and past use of ARBs had adjusted ORs of 1.38 (0.79–2.41) and 0.27 (0.05–1.51), respectively. Conclusions: Use of ACE inhibitors or ARBs is not associated with an increased risk of developing RA. (aut. ref.)

ObjectivesStatins offer significant cardiovascular benefits. Their use, however, influences immune regulation, which may potentially facilitate autoimmunity, eventually resulting in autoimmune diseases such as rheumatoid arthritis (RA).The authors studied whether statin use was associated with an increased risk of developing RA by conducting a case–control study using the Netherlands Information Network of General Practice database.MethodsThe authors identified 508 patients aged 40 years or older with a first-time diagnosis of RA in the period 2001–2006. Each RA case was matched to five controls for age, sex and index date, which was selected 1 year before the first diagnosis of RA. Odds ratios for the first-time diagnosis of RA were verified by a referral to a rheumatologist and/or at least one prescription of disease-modifying anti-rheumatic drugs and/or two prescriptions of corticosteroids after the date of first diagnosis.ResultsCases were more often users of statins (15.9%) compared to controls (8.6%). After adjustment for cardiovascular risk factors and use of comedication, statin use was associated with an increased risk of incident RA (adjusted OR, 1.71 (95% CI 1.16 to 2.53); p=0.007). A consistent trend of increasing risk with increased cumulative duration, cumulative defined daily doses and number of prescriptions was not observed. However, a small trend between the potency of statin treatment and the risk of RA was found.ConclusionsStatin use seems to be associated with an increased risk of developing RA. Our findings should be replicated by additional studies.

The nature and the velocities of the reactions occurring in concentrated solutions of urea and formaldehyde may be very similar to what is found in dilute systems. A rapid initial reaction between urea and formaldehyde, as reported in literature, was not observed and is shown to be due to the analytical methods used.

The hydrolysis of methylene diurea giving urea and monomethylolurea was found to be a monomolecular reaction. The rate of the reaction is directly proportional to the hydrogen ion concentration in the pH range measured (3-5) and independent of the buffer concentration. The activation energy appeared to be 19.5 kcal. Generally, the reaction of an amidomethylol group with an amide group leading to the formation of a methylene bridge between urea fragments, will be a reversible reaction. The rates of both the forward and the reverse reactions are proportional to the hydrogen ion concentration.

The reaction of methylene diurea with formaldehyde showed a close resemblance to the previously studied reaction of urea and formaldehyde1), i.e. the reaction appeared to be bimolecular and the rates were found to be directly proportional to the concentration of hydroxyl ions while further an influence of the buffer concentration on the rates was observed. Obviously the reaction is subject to a general acid and/or base catalysis. The activation energy appeared to be about 15 kcal/mol. The values for the rate constants were almost the same as were found for the reaction between urea and formaldehyde.

The reaction of urea and formaldehyde, giving monomethylolurea, is reversible in a neutral, acid or alkaline aqueous solution, the forward reaction being bimolecular and the reverse reaction monomolecular. The forward and reverse reactions are catalyzed to the same extent by hydrogen ions as well as by hydroxyl ions. The specific rates are directly proportional to the hydrogen and hydroxyl ion concentrations. There appears to be an influence of the buffer concentration on the reaction rates probably due to a general acid and general base catalysis. The equilibrium is almost independent of the pH of the solution and of the buffer concentrations. The activation energies of the forward and the reverse reaction have been determined, giving the heat of reaction. Within experimental error these activation energies may be the same for the non-catalyzed and for the catalyzed system. The reaction mechanism is discussed.

The formation and decomposition of dimethylolurea shows a close resemblance to that of monomethylolurea previously studied1 a) The reaction between formaldehyde and monomethylurea giving dimethylolurea leads to an equilibrium which can be reached from both sides. The equilibrium is independent of the pH of the solution. b) The formation of dimethylolurea from formaldehyde and monomethylolurea appeared to be a bimolecular reaction. The decomposition of dimethylolurea is monomolecular. c) Both reactions are catalyzed to the same extent by hydrogen ions and by hydroxyl ions and there is an influence of the buffer concentration on the velocity. The reaction rates are found to be directly proportional to the hydrogen and hydroxyl—ion concentrations. d) The activation energies have been determined. Within experimental error these energies were found to be about the same as the activation energies of the monomethylolurea formation and decomposition, viz. 14 and 19 kcal/mole. The reaction mechanism is briefly discussed. The formation of trimethylolurea could not be observed.

Some condensates of urea and formaldehyde were prepared from solutions of pH 2-7 at temperatures of 20-76° C. These products have been analysed with respect to their content of methylene groups, methylol groups and urea groups. The average molecular weights could be estimated. The analytical data are in harmony with the occurrence of methylene bridges between the urea fragments. The condensates will be formed by a stepwise condensation reaction. “Methylene urea” may be a mixture of condensates with an average molecular weight of 300-500.

The hydroxymethylation of phenols has been investigated in the pH range 1-11 and between 70-130° C in dilute aqueous solution. The reaction appeared to be bimolecular. Below about pH = 4 the rates were found to be proportional to the concentration of the hydrogen ions, while a proportionality to the concentration of the hydroxyl ions was observed in more alcaline solutions. An influence of the concentration of buffers on the rates has not been observed. The presence of small amounts of triethanolamine does not influence the rate of the reaction. The mechanism of the reaction is discussed.

The reaction between monomethylolurea and methylene diurea appeared to be bimolecular and the rate constants were found to be directly proportional to the concentration of the hydrogen ions. An influence of the buffer concentration was not observed. The activation energy was found to be 15 kcal/mol.

Some aspects of the alkylation of phenol with isobutene using small quantities of sulfuric acid as a catalyst are discussed. It is shown that initially ortho and para substitution take place to roughly the same extent. In the course of the reaction the isomer distribution changes in favour of the para isomer, the alkylation being reversible. Equilibrium constants were determined in the temperature range of 50-125°.

Introduction: The impact of muscle contraction upon head movements induced by a forward acceleration was studied as a model for low impact car-accidents. The purpose of our research is to examine: (i) whether and by which mechanism neck muscle contraction is induced after onset of the movement; and (ii) if voluntary neck muscle contraction prior to the movement affects head motion. Subjects and methods: Eight healthy volunteers (mean age 21.4 years) were included in this study. Volunteers were sitting on a standard car seat mounted on a sled. The computer-controlled, motor-driven sled was forward accelerated with 0.6 g. In test series 1, head and body movement were detected with a standard video camera (20 ms per frame) and accelerometers mounted on the head without interference with muscle activity. Muscle activation was detected by simultaneous measurement of surface EMG of m. splenius capitis, m. trapezius (descending part), m. scalenis medius, m. sternocleido mastoideus, m. digastricus (anter...

Testing complex systems, such as the ASML TWINSCAN lithographic machine, is expensive and time consuming. In a previous work, a test sequencing method to calculate time-optimal test sequences has been developed. Because complex systems are composed of several subsystems, which are again composed of several modules, there exists a need to hierarchically model test sequencing problems. Such a hierarchical test sequencing problem consists of a high-level model that describes a test sequencing problem at the system level, and one or more low-level models that describe the test sequencing problems at the subsystem or module level. The tests at the system level correspond to the solutions of low-level problems. This paper describes a hierarchical test sequencing model and proposes two algorithms to compute an optimal test sequence. The benefits of hierarchically modeling a problem are less computational effort and less modeling effort, because not all relations are needed. This is illustrated by a small example. The industrial relevance of this method is illustrated on a case study related to a manufacturing testing phase of a lithographic machine.

Cross-contamination and undercooking are major factors responsible for campylobacteriosis and as such should be incorporated in microbiological risk assessment. A previous paper by van Asselt et al.((1)) quantified cross-contamination routes from chicken breast fillet via hand, cutting board, and knife ending up in a prepared chicken-curry salad in the domestic kitchen. The aim of the current article was to validate the obtained transfer rates with consumer data obtained by video observations and microbial analyses of a home prepared chicken-curry salad. Results showed a wide range of microbial contamination levels in the final salad, caused by various cross-contamination practices and heating times varying from 2'44'' to 41'30''. Model predictions indicated that cooking times should be at least 8 minutes and cutting boards need to be changed after cutting raw chicken in order to obtain safe bacterial levels in the final salad. The model predicted around 75% of the variance in cross-contamination behavior. Accuracy of the model can further be improved by including other cross-contamination routes besides hands, cutting boards, and knives. The model proved to be fail-safe, which implies it can be used as a worst-case estimate to assess the importance of cross-contamination in the home.

The improvement of food safety in the domestic environment requires a transdisciplinary approach, involving interaction between both the social and natural sciences. This approach is applied in a study on risks associated with Campylobacter on broiler meat. First, some web-based information interventions were designed and tested on participant motivation and intentions to cook more safely. Based on these self-reported measures, the intervention supported by the emotion "disgust" was selected as the most promising information intervention. Its effect on microbial cross-contamination was tested by recruiting a set of participants who prepared a salad with chicken breast fillet carrying a known amount of tracer bacteria. The amount of tracer that could be recovered from the salad revealed the transfer and survival of Campylobacter and was used as a measure of hygiene. This was introduced into an existing risk model on Campylobacter in the Netherlands to assess the effect of the information intervention both at the level of exposure and the level of human disease risk. We showed that the information intervention supported by the emotion "disgust" alone had no measurable effect on the health risk. However, when a behavioral cue was embedded within the instruction for the salad preparation, the risk decreased sharply. It is shown that a transdisciplinary approach, involving research on risk perception, microbiology, and risk assessment, is successful in evaluating the efficacy of an information intervention in terms of human health risks. The approach offers a novel tool for science-based risk management in the area of food safety.

Testing complex manufacturing systems, like ASML lithographic machines, can take up to 45% of the total development time. The decision of when to stop testing is often difficult to make because less testing may leave critical faults in the system, while more testing increases time-to-market. In this paper, we solve the problem of deciding when to stop testing by introducing a test-sequencing method that incorporates several stopping criteria. These stopping criteria consist of objectives and constraints on the test cost and the remaining risk cost. For a given problem, a suitable stopping criterion can be chosen. For example, with the risk-based stopping criterion, testing stops when the test time or cost exceeds the risk cost. Furthermore, we show that it also is possible to model reliability problems with this test-sequencing method. The method is demonstrated on ASML systems with two case studies. The first case study was conducted in the test phase during the development of the software that is used to control an ASML lithographic machine. The second case study was conducted on the reliability testing of a lithographic machine.

It has been established that, to a considerable extent, the domestic hygiene practices adopted by consumers can result in a greater or lesser microbial load in prepared meals. In the research presented here, an interdisciplinary study is reported in which interviews, observations of consumers preparing a recipe, and microbial contamination of the finished meals were compared. The results suggest that, while most consumers are knowledgeable about the importance of cross-contamination and heating in preventing the occurrence of foodborne illness, this knowledge is not necessarily translated into behavior. The adoption of habitual cooking practices may also be important. Potentially risky behaviors were, indeed, observed in the domestic food preparation environment. Eighteen of the participants made errors in food preparation that could potentially result in cross-contamination, and seven participants allowed raw meat juices to come in contact with the final meal. Using a tracer microorganism the log reduction as a result of consumer preparation was estimated at an average of log 4.1 cfu/salad. When combining these findings, it was found that cross-contamination errors were a good predictor for log reduction. Procedural food safety knowledge (i.e., knowledge proffered after general open questions) was a better predictor of efficacious bacterial reduction than declarative food safety knowledge (i.e., knowledge proffered after formal questioning). This suggests that motivation to prepare safe food was a better indicator of actual behavior than knowledge about food safety per se.

Microbial food safety has been the focus of research across various disciplines within the risk analysis community. Natural scientists involved in food microbiology and related disciplines work on the identification of health hazards, and the detection of pathogenic microorganisms. To perform risk assessment, research activities are increasingly focused on the quantification of microbial contamination of food products at various stages in the food chain, and modeling the impact of this contamination on human health. Social scientists conduct research into how consumers perceive food risks, and how best to develop effective risk communication with consumers in order to improve public health through improved food handling practices. The two approaches converge at the end of the food chain, where the activities regarding food preparation and food consumption are considered. Both natural and social sciences may benefit from input and expertise from the perspective of the alternative discipline, although, to date, the integration of social and natural sciences has been somewhat limited. This article therefore explores the potential of a transdisciplinary approach to food risk analysis in terms of delivering additional improvements to public health. Developing knowledge arising from research in both the natural and social sciences, we present a novel framework involving the integration of the two approaches that might provide the most effective way to improve the consumer health associated with food-borne illness.

Clostridium perfringens is a pathogen that mainly causes food poisoning outbreaks when large quantities of food are prepared. Therefore, a model was developed to predict the effect of different cooling procedures on the growth of this pathogen during cooling of food: Dutch pea soup. First, a growth rate model based on interpretable parameters was used to predict growth during linear cooling of pea soup. Second, a temperature model for cooling pea soup was constructed by fitting the model to experimental data published earlier. This cooling model was used to estimate the effect of various cooling environments on average cooling times, taking into account the effect of stirring and product volume. The growth model systematically overestimated growth of C. perfringens during cooling in air, but this effect was limited to less than 0.5 log N/ml and this was considered to be acceptable for practical purposes. It was demonstrated that the growth model for C. perfringens combined with the cooling model for pea soup could be used to sufficiently predict growth of C. perfringens in different volume sizes of pea soup during cooling in air as well as the effect of stirring, different cooling temperatures, and various cooling environments on the growth of C. perfringens in pea soup. Although fine-tuning may be needed to eliminate inaccuracies, it was concluded that the combined model could be a useful tool for designing good manufacturing practices (GMP) procedures.

Repetitive pulsed power techniques have enormous potential for a wide range of applications, such as nano-particle and hydrogen production, gas and water processing and sterilization, and generation of X-ray, EUV, and high-power acoustics. This paper presents the state of the art of our activities on repetitive ultra-short and microsecond pulsed power sources, pulsed thermal and streamer corona plasmas. Critical circuit elements are heavy-duty thyristors, transmission line transformers, and triggered spark-gap switches.

Background: Pre- or reconditioning of donor livers can improve organ quality prior to transplantation. The aim of this study was to investigate whether metformin as pre- or reconditioning agent is able to reduce preservation injury in rat donor livers and improve hepatobiliary function during ex situ normothermic machine perfusion (NMP). Methods: To study the preconditioning effects of metformin, metformin was administered via oral gavage 12 and 2 hours before the hepatectomy. To assess the reconditioning effects of metformin, in 2 other groups, metformin was added to the NMP perfusion fluid in two different concentrations (30 and 300 mg/L). In the reference group, no pre- or reconditioning was carried out. In all groups, rat donor livers were preserved for 4 hours in preservation fluid on melting ice. Thereafter, NMP was performed for viability assessment. Results: Preconditioning improved ATP production and hepatobiliary function (assessed by total bile production, biliary bilirubin and bicarbonate) and significantly lowered levels of lactate and glucose during NMP. On the other hand, metformin preconditioning did not reduce markers for hepatobiliary injury such as AST, ALT, LDH, caspase-3 activity, TBARS or biliary gamma-GT and LDH. Reconditioning with metformin did not improve hepatobiliary function or reduce injury markers during NMP. Conclusion: Preconditioning of rat donor livers with metformin improves hepatobiliary function but does not reduce preservation injury as assessed during 3 hours of NMP. Reconditioning with metformin showed no beneficial effects.

It was with great interest that we read the correspondence of Abud-Mendoza1 on our recent paper in which we described a decreased risk of developing systemic lupus erythematosus (SLE) in statin users who continued their therapy for >1 year.2 We agree that prevention of cardiovascular disease in rheumatic diseases is of great importance.3 Whether statins decrease disease activity in SLE is, however, controversial since a recent meta-analysis of five controlled trials did not suggest any significant effect of statin therapy on Systemic Lupus Erythematosus Disease Activity Index.4 Unfortunately, in the UK’s Clinical Practice Research Datalink (CPRD)—an ongoing primary care database of anonymised medical records from general practitioners that was used in our study—no measurements for SLE activity before or after initiating statin therapy are available.2 We, however, do not think that statin …

The working alliance between therapist and patient has been investigated frequently, but much less is known about the working alliance in specific patient groups in specific settings.To obtain insight into the characteristics of the working alliance in intensive inpatient psychotherapy involving patients with severe personality disorders, and to pay special attention to patient characteristics such as diagnosis and attachment.At the end of the first phase of treatment we collected, on the basis of questionnaires, information about the working alliance and attachment of 60 patients with a severe personality disorders who had received inpatient psychotherapy.Working alliances with therapist and team were found to be weaker than in outpatient populations; working alliances with the therapist proved to be stronger than working alliances with the treatment team. Cluster C patients developed a better working alliance with the treatment team than did cluster B patients, particularly in the domain of treatment goals. Patients in this study turned out to be attached more anxiously and 'avoidantly' than patients in general outpatient populations; no correlation was found between patients' attachment and the strength of the working alliance. However, when a distinction was made between patients with extreme scores and patients with average scores, results showed that the more anxiously patients felt attached, the higher were their scores for their working alliance with the treatment team.It is more difficult to establish a working alliance with patients who have a severe personality disorder than with patients suffering from a less severe personality disorder. Patients with a severe personality disorder seemed to show a higher degree of anxious attachment and to have a more critical attitude to the working alliance.

Microcrystals of 1,1‘-bicyclohexyliden-4-one oxime (oxime) were prepared with the spin-coating technique. In these crystals, the oxime molecules form dimers through intermolecular hydrogen bonding. In this orientation, the crystals have a hydrophobic surface. The crystals were imaged with atomic force microscopy (AFM) at three different temperatures, i.e., 16, 20, and 30 °C. We show that it is possible to break the dimeric hydrogen bond with the AFM tip. The force necessary to accomplish this is temperature dependent and increases with decreasing temperature; its magnitude is on the order of the strength of the dimer bond. Breaking of the dimeric hydrogen bonds only occurs near the step edges. In these regions, a clear contrast in friction imaging was observed with lateral force microscopy together with a reduction of the step height to half the original value. We interpreted this as the removal of one layer of oxime molecules resulting in an (oxime-terminated) hydrophilic surface with a higher friction c...

We present a new procedure to prepare high-quality colloidal crystals at a flat wall, which was oriented vertically in a colloidal suspension. The method is based on the depletion-induced effective attraction between the colloidal particles themselves and between the colloidal particles and a flat wall. The concentrations of the colloidal particles and the depletion agents (polymers in this case) were chosen in such a way that phase transition occurred not only at the wall but also in the bulk. In this way, good conditions were obtained to form high-quality colloidal crystals, consisting of several layers, at a flat wall in a relatively short time period. The crystals formed were characterized with atomic force microscopy.

Chronic hypertension during aging is a serious threat to the cerebral vasculature. The larger brain arteries can react to hypertension with an abnormal wall thickening, a loss of elasticity and a narrowed lumen. However, little is known about the hypertension-induced alterations of cerebral capillaries. The present study describes ultrastructural alterations of the cerebrocortical capillary wall, such as thickening and collagen accumulation in the basement membrane of aging spontaneously hypertensive stroke-prone rats. The ratio of cortical capillaries with such vascular pathology occurred significantly more frequently in hypertensive animals. Nimodipine and nifedipine are potential drugs to decrease blood pressure in hypertension but their beneficial effects in experimental studies reach beyond the control of blood pressure.Nimodipine and nifedipine can alleviate ischemia-related symptoms and improve cognition. These drugs differ in that nifedipine, but not nimodipine reduces blood pressure at the here-used concentration while both drugs can penetrate the blood-brain barrier. Here we show that chronic treatment of aging hypertensive stroke-prone rats with nimodipine or nifedipine could preserve microvascular integrity in the cerebral cortex. (C) 2001 Elsevier Science Inc. All rights reserved.

In concentrated aqueous solution and in the presence of an excess of formaldehyde more than two methylol groups may be attached to one molecule of urea. The equilibrium constant of the formation of trimethylol urea is evaluated.

Cerebral capillaries represent a major interface between the general circulation and the central nervous system and are responsible for sufficient and selective nutrient transport to the brain. Structural damage or dysfunctioning carrier systems of such an active barrier leads to compromised nutrient trafficking. Subsequently, a decreased nutrient availability in the neural tissue may contribute to hampered neuronal metabolism, hence to behavioral and cognitive functional deficiencies. Here we focus on the ultrastrucutral abnormalities of cerebral microvessels in Alzheimer's disease (AD; n = 5) and Parkinson's diseasse (PD; n = 10). The capillary microanatomy in samples from the cingulate cortex was investigated by electron microscopy and severe damage to the vessel walls was observed. Characteristic pathological changes including capillary basement membrane thickening and collagen accumulation in the basement membrane were enhanced in both AD and PD. The incidence of capillaries with basement membrane deposits was two times higher in AD and PD than in age-matched controls. Degenerative pericytes in all groups appeared at a similar frequency. The data indicate that basement membrane deposists, as opposed to pericytic degeneration, represent an important pathological feature of AD and PD and suggest that capillary dysfunction may play a causal role in the development of these two major neurodegenerative diseases.