Probing the gas-phase structure of charge-tagged intermediates of a proline catalyzed aldol reaction - vibrational spectroscopy distinguishes oxazolidinone from enamine species.

An l-proline based catalyst with a charged phenyl-pyridium substituent (1) was used to analyze intermediates of an organocatalyzed aldol reaction by infrared multi-photon dissociation (IRMPD) mass spectrometry after transfer into the gas phase via electrospray ionization (ESI). IRMPD spectra were interpreted with the aid of density functional theory (DFT) computations. A structurally restricted enamine species was used as a reference molecule for the calculated vibrational frequencies. A close correlation between theory and experiment was found for the energetically most favoured oxazolidinone structures.

Mechanistic studies of an L-proline-catalyzed pyridazine formation involving a Diels-Alder reaction with inverse electron demand.

The mechanism of an L-proline-catalyzed pyridazine formation from acetone and aryl-substituted tetrazines via a Diels-Alder reaction with inverse electron demand has been studied with NMR and with electrospray ionization mass spectrometry. A catalytic cycle with three intermediates has been proposed. An enamine derived from L-proline and acetone acts as an electron-rich dienophile in a [4 + 2] cycloaddition with the electron-poor tetrazine forming a tetraazabicyclo[2.2.2]octadiene derivative which then eliminates N2 in a retro-Diels-Alder reaction to yield a 4,5-dihydropyridazine species. The reaction was studied in three variants: unmodified, with a charge-tagged substrate, and with a charge-tagged proline catalyst. The charge-tagging technique strongly increases the ESI response of the respective species and therefore enables to capture otherwise undetected reaction components. With the first two reaction variants, only small intensities of intermediates were found, but the temporal progress of reactants and products could be monitored very well. In experiments with the charge-tagged L-proline-derived catalyst, all three intermediates of the proposed catalytic cycle were detected and characterized by collision-induced dissociation (CID) experiments. Some of the CID pathways of intermediates mimic single steps of the proposed catalytic cycle in the gas phase. Thus, the charge-tagged catalyst proved one more time its superior effectiveness for the detection and study of reactive intermediates at low concentrations.

Safety, Feasibility, and Efficiency of a New Cooling Device Using Intravenous Cold Infusions for Fever Control.

BACKGROUND: Fever control plays a key role in therapy of patients with acute brain injury. The infusion of cold saline could serve as an alternative or additional method for targeted temperature management. However, it is difficult to estimate the amount of fluid required to achieve normothermia merely on the basis of body weight. There is no standardized load management regarding the administration of cold saline, and no closed-loop systems based on continuous temperature-controlled feedback are available. The primary purpose of the present study was to evaluate the feasibility, efficacy, and safety of a new automated fluid infusion system. METHODS: Twelve patients with acute brain injury and febrile episodes were treated with the automated infusion device tempedy (seiratherm GmbH, Herzogenaurach, Germany). Patients were included if bladder temperature still was ≥ 37.9 °C after administration of antipyretic medication, cold washing solutions, and ice packs more than 2 h earlier. The efficacy was examined by measuring the time and amount of fluid needed to reach and maintain target temperature. Feasibility and safety were assessed based on recording any technical difficulties with the new device and the occurrence of clinical signs of fluid overload such as acute pulmonary edema, electrolyte disturbances, or acid-base dysfunction. RESULTS: The mean time was 73 min (range from 15 to 330 min) and 1650 ml the mean amount of fluid (21.2 ml/kg; SD 28.5 ml/kg) to reach the target temperature. The mean total fluid balance to reach and maintain the target temperature in the first 12 h was 1350 ml (SD 1550 ml). In the first 12 h 89.4% of the time temperature values were in the target range (median 95.3%, range 83.8-10%). No clinical signs of fluid overload such as an acute pulmonary edema or device-related adverse events occurred. CONCLUSION: Target temperature management with the new automated infusion device is feasible. Although we provided first data regarding safety, further controlled randomized studies are needed to evaluate the long-time safety, as well as the best indications and timing for this cooling device.

Multicentre randomized clinical trial of inspiratory muscle training versus usual care before surgery for oesophageal cancer.

BACKGROUND: Up to 40 per cent of patients undergoing oesophagectomy develop pneumonia. The aim of this study was to assess whether preoperative inspiratory muscle training (IMT) reduces the rate of pneumonia after oesophagectomy. METHODS: Patients with oesophageal cancer were randomized to a home-based IMT programme before surgery or usual care. IMT included the use of a flow-resistive inspiratory loading device, and patients were instructed to train twice a day at high intensity (more than 60 per cent of maximum inspiratory muscle strength) for 2 weeks or longer until surgery. The primary outcome was postoperative pneumonia; secondary outcomes were inspiratory muscle function, lung function, postoperative complications, duration of mechanical ventilation, length of hospital stay and physical functioning. RESULTS: Postoperative pneumonia was diagnosed in 47 (39·2 per cent) of 120 patients in the IMT group and in 43 (35·5 per cent) of 121 patients in the control group (relative risk 1·10, 95 per cent c.i. 0·79 to 1·53; P = 0·561). There was no statistically significant difference in postoperative outcomes between the groups. Mean(s.d.) maximal inspiratory muscle strength increased from 76·2(26·4) to 89·0(29·4) cmH2 O (P < 0·001) in the intervention group and from 74·0(30·2) to 80·0(30·1) cmH2 O in the control group (P < 0·001). Preoperative inspiratory muscle endurance increased from 4 min 14 s to 7 min 17 s in the intervention group (P < 0·001) and from 4 min 20 s to 5 min 5 s in the control group (P = 0·007). The increases were highest in the intervention group (P < 0·050). CONCLUSION: Despite an increase in preoperative inspiratory muscle function, home-based preoperative IMT did not lead to a decreased rate of pneumonia after oesophagectomy. Registration number: NCT01893008 (https://www.clinicaltrials.gov).

Investigations of the Copper-Catalyzed Oxidative Cross-Coupling of Tetrahydroisoquinolines with Diethylzinc by a Combination of Mass Spectrometric and Electrochemical Methods.

The aerobic oxidative cross-coupling of tetrahydroisoquinolines (THIQs) with diethylzinc catalyzed by CuCl2 has been examined by means of electrospray mass spectrometry (ESI-MS). Substrates, intermediates, and the product were readily detected. Particular emphasis has been placed on the role of CuCl2 . Formation of the intermediate iminium species has been investigated in more detail by ESI-MS, electrochemistry-coupled ESI mass spectrometry (EC-MS), and cyclic voltammetry (CV). Our experiments have consistently revealed strong influences of the N-substituent of the THIQ derivative and its oxidation stability with respect to CuCl2 . The results may help to expand the synthetic scope of the reaction, while also further establishing EC-MS as a valuable technique for linking mass spectrometry with cyclic voltammetry in mechanistic studies of organic redox reactions.

A new charge-tagged proline-based organocatalyst for mechanistic studies using electrospray mass spectrometry.

A new 4-hydroxy-L-proline derivative with a charged 1-ethylpyridinium-4-phenoxy substituent has been synthesized with the aim of facilitating mechanistic studies of proline-catalyzed reactions by ESI mass spectrometry. The charged residue ensures a strongly enhanced ESI response compared to neutral unmodified proline. The connection by a rigid linker fixes the position of the charge tag far away from the catalytic center in order to avoid unwanted interactions. The use of a charged catalyst leads to significantly enhanced ESI signal abundances for every catalyst-derived species which are the ones of highest interest present in a reacting solution. The new charged proline catalyst has been tested in the direct asymmetric inverse aldol reaction between aldehydes and diethyl ketomalonate. Two intermediates in accordance with the List-Houk mechanism for enamine catalysis have been detected and characterized by gas-phase fragmentation. In addition, their temporal evolution has been followed using a microreactor continuous-flow technique.

Maternal depression, family functioning and children's longitudinal development.

Analysis of data from the Canadian National Longitudinal Survey of Children and Youth reveals that 6% of children are born to mothers who experienced symptoms of depression during their first 2 years of life. The prevalence rises steadily until children are 10 years of age when it reaches 9%, and thereafter remains relatively stable. Children of depressed mothers are at increased risk of having low receptive vocabulary and displaying inattention or physical aggression at ages 4 to 5 years, only partially attributable to family demographic factors, family functioning and parenting qualities. Maternal depression occurring when the child was 2 to 3 years of age, was a risk factor for anxiety in 10 and 11 year olds. Timing or duration of maternal depression had no effect on math achievement. The risk of poor child outcome was greatest for mothers who experienced depression continuously or when their child was 2 to 3 years or older. Nurses need to assess and intervene to reduce the impact of depression on mothers and their children's development, well beyond the postpartum period.

The family antecedents and the subsequent outcomes of early puberty.

The purpose of this study was to examine both the family antecedents and the outcomes of early puberty, with a particular focus on factors related to family socioeconomic status (SES). The study employed a comprehensive measurement of pubertal development and longitudinal data from the Canadian National Longitudinal Survey of Children and Youth. The sample (N = 8,440; 49% girls) included four cohorts of children who were followed biennially for 10 years, starting from age 4-11 to 14-21 years. Data were drawn at different years of age from these cohorts of children. Girls whose fathers were unemployed were more likely to experience early puberty than those whose fathers were employed. For boys, those living with fathers who had not finished secondary school were more likely to experience early puberty. Early maturing girls tended to engage in smoking and drinking at an earlier age compared with their peers. These findings provide support for psychosocial acceleration theory and suggest that different aspects of low family SES may act as a psychosocial stress for early pubertal maturation in boys versus girls, which may lead to engagement in drinking and smoking at a younger age, at least for girls.

Neighborhood poverty and early transition to sexual activity in young adolescents: a developmental ecological approach.

This study examined how the link between neighborhood poverty and the timing of sexual initiation varies as a function of age, gender, and background characteristics. A sample of N = 2,596 predominately White Canadian adolescents from the National Longitudinal Survey of Children and Youth was used. Sexual initiations occurring between 12 and 15 years old were considered. Results showed that younger adolescent females who lived in poor neighborhoods and who had a history of conduct problems were more likely to report early sexual activity. Peer characteristics partly accounted for this susceptibility. Among adolescent males, no direct neighborhood effects were found, but those who had combined risks at multiple levels appeared more vulnerable. The theoretical and practical implications of these findings are discussed.

Affiliation to youth gangs during adolescence: the interaction between childhood psychopathic tendencies and neighborhood disadvantage.

Because youth gangs tend to cluster in disadvantaged neighborhoods, adolescents living in such neighborhoods are more likely to encounter opportunities to join youth gangs. However, in the face of these opportunities, not all adolescents respond in the same manner. Those with preexisting psychopathic tendencies might be especially likely to join. In this study, we tested whether a combination of individual propensity and facilitating neighborhood conditions amplifies the probabilities of youth gang affiliation. A subset of 3,522 adolescents was selected from a nationally representative, prospective sample of Canadian youth. Psychopathic tendencies (i.e., a combination of high hyperactivity, low anxiety, and low prosociality as compared to national norms) were assessed through parent reports, while neighborhood characteristics (i.e., concentrated economic disadvantage and residential instability) were derived from the 2001 Census of Canada. Our results indicated that neighborhood residential instability, but not neighborhood concentrated economic disadvantage, interacted with individual propensity to predict youth gang membership. Adolescents with preexisting psychopathic tendencies appeared especially vulnerable mainly if they were raised in residentially unstable neighborhoods.

Patterns and correlates of pubertal development in Canadian youth: effects of family context.

BACKGROUND: Current health literature suggests that there has been a decline in the age of pubertal onset, and that pubertal development is influenced by social context. Unfortunately, contemporary Canadian-specific data have not been available. This study examined the odds of having entered puberty at various ages during adolescence, before and after controlling for the effects of family socio-economic status and family structure. METHODS: Longitudinal data for this study were drawn from the first four cycles of the National Longitudinal Survey of Children and Youth. The final sample consisted of 7977 adolescents ranging in age from 10 to 17. Pubertal status of the participants was identified based on pubic hair, facial hair growth, and voice change, for boys; and pubic hair, breast development, and menstruation, for girls. Trajectories of pubertal development were analyzed with HLM growth curve modelling techniques. RESULTS: The results indicated that, compared to boys, the odds of having entered puberty at age 13 were 6.45 times higher for girls and that girls go through puberty more quickly. Low family socio-economic status and living with a stepfather were found to predict early onset of pubertal development. CONCLUSION: Contextual factors are related to pubertal development. Additional research is needed to develop a more solid understanding of how psychosocial factors interact to predict gendered patterns of pubertal development.

Community unemployment and immigrants' health in Montreal.

This research examines the relationship between community unemployment and the physical and mental health of immigrants in comparison to non-immigrants in Montreal under the hypothesis that high unemployment in the community may generate more negative effects on the health of immigrants than on non-immigrants. Possible gender differences in these associations are also examined. Montreal residents were studied via multilevel analysis, using both individual survey data and neighbourhood data from 49 police districts. Individual-level data were excerpted from a 1998 health survey of Montreal residents, while neighbourhood data originated from survey data collected in the 49 Montreal police districts and the 1996 Canadian Census. The associations between community unemployment and self-rated health, psychological distress and obesity are examined, and hypotheses regarding the modifying mechanisms via which male and female immigrants may run a greater risk of poor health than non-immigrants when living in areas of high unemployment were tested. Between neighbourhoods, variations in the three health outcomes were slight, and differences in health were not associated with differences in community unemployment. The associations between community unemployment and health varied according to immigration status. At the individual level, immigrants do not differ from non-immigrants with respect to the three health indicators, except that second-generation males are slightly heavier. However, when living in areas of high unemployment, immigrants tend to report poor physical and mental health in comparison to non-immigrants. Among first-generation immigrants, community unemployment was associated with psychological distress. Among second-generation immigrants, the probability of obesity and poor self-rated health increased significantly for those living in areas with high unemployment, but these associations reached statistical significance only for men. Findings among first-generation immigrants are interpreted with respect to the effects of possible discrimination in areas with low job availability. Among second-generation men, poor physical health and obesity may be the result of poor health habits stemming from perceived lack of life opportunities.

Is the Canadian childhood obesity epidemic related to physical inactivity?

OBJECTIVE: This study examined the relation among children's physical activity, sedentary behaviours, and body mass index (BMI), while controlling for sex, family structure, and socioeconomic status. DESIGN: Epidemiological study examining the relations among physical activity participation, sedentary behaviour (video game use and television (TV)/video watching), and BMI on a nationally representative sample of Canadian children. SUBJECTS: A representative sample of Canadian children aged 7-11 (N=7216) from the 1994 National Longitudinal Survey of Children and Youth was used in the analysis. MEASUREMENTS: Physical activity and sport participation, sedentary behaviour (video game use and TV/video watching), and BMI measured by parental report. RESULTS: Both organized and unorganized sport and physical activity are negatively associated with being overweight (10-24% reduced risk) or obese (23-43% reduced risk), while TV watching and video game use are risk factors for being overweight (17-44% increased risk) or obese (10-61% increased risk). Physical activity and sedentary behaviour partially account for the association of high socioeconomic status and two-parent family structure with the likelihood of being overweight or obese. CONCLUSION: This study provides evidence supporting the link between physical inactivity and obesity of Canadian children.

Geographic and demographic variation in the prevalence of overweight Canadian children.

OBJECTIVE: To examine the geographic and demographic variation in the prevalence of overweight Canadian children. RESEARCH METHODS AND PROCEDURES: Using BMI data from the 1981 Canada Fitness Survey and the 1996 National Longitudinal Survey of Children and Youth, this study assessed: 1). the prevalence of overweight and obesity among Canadian boys and girls ages 7 to 13 years; 2). secular trends in the prevalence of overweight from 1981 to 1996, by province and adjusted for age and sex; and 3). provincial variation in the prevalence of overweight, before and after adjusting for socioeconomic and demographic characteristics. RESULTS: The prevalence of boys and girls classified as overweight in 1996 was 33% and 26%, respectively. The corresponding figures for obesity were 10% for boys and 9% for girls. Provincial variation was observed with a trend of increasing risk of being overweight from west to east. Socioeconomic status was inversely related to the prevalence of overweight regardless of geographic region. The risk of being overweight was more related to geography (province) than demographic variables (income and family background); however, the effect of secular trends (1981 to 1996) exceeded the effect of geographic or demographic variables. DISCUSSION: The prevalence of childhood overweight and obesity is increasing in all areas of Canada and can be explained only partially by geographic or demographic characteristics.

Temporal trends in overweight and obesity in Canada, 1981-1996.

OBJECTIVE: To assess changes in the prevalence of overweight and obesity among Canadian children and adults between 1981 and 1996 using recent recommendations for the classification of overweight and obesity. DESIGN: Epidemiological study comparing the prevalence of overweight and obesity from the 1981 Canada Fitness Survey (CFS) to the 1996 National Longitudinal Survey of Children and Youth (NLSCY) and the 1996 National Population Health Survey (NPHS). SUBJECTS: Adults 20-64 y of age and children 7-13 y of age from the CFS, NLSCY and NPHS. MEASUREMENTS: BMI was calculated from directly measured or self-reported body mass and height. For adults 20-64 y of age, overweight and obesity were defined as BMI > or = 25 kg/m2 and BMI > or = 30 kg/m2, respectively. Age- and sex-specific cut-off points for children that correspond to the adulthood categories were used to define overweight and obesity for children 7-13 y of age. RESULTS: The prevalence of overweight increased from 48 to 57% among men and from 30 to 35% among women, while the prevalence of obesity increased from 9 to 14% in men and from 8 to 12% in women. The corresponding increases were from 11 to 33% in boys and from 13 to 27% in girls for overweight and from 2 to 10% in boys and from 2 to 9% in girls for obesity. CONCLUSION: The results indicate dramatic increases in the prevalence of both overweight and obesity in Canada over the last 15 y, and the problem is particularly pronounced among children.

Women's Adaptation to Chronic Back Pain: Daily Appraisals and Coping Strategies, Personal Characteristics and Perceived Spousal Responses.

Daily diary methodology was used to examine within- and between-person associations among pain appraisals, coping strategies, personal characteristics, perceived spousal responses and daily (30 days) changes in negative mood and pain for 88 women with chronic back pain. Multilevel models revealed that control appraisals and distraction and ignoring pain coping strategies were associated with same-day reductions in negative mood and pain; whereas catastrophizing appraisals and praying and hoping coping strategies were associated with an increase in negative mood or pain. With appraisals and coping controlled for, average within-day decreases in depression were associated with perceived control in one's life; increases in anxiety were associated with spousal distracting responses; and increases in pain intensity were associated with spousal punishing responses and pain interference.

Preliminary evaluation of a video questionnaire to assess activity levels of children.

PURPOSE: The purpose of this study was to explore the validity of the Assessment of Young Children's Activity Using Video Technology (ACTIVITY) self-report instrument in assessing previous-day physical activity. METHODS: Forty-seven third-grade children (mean age 7.72 +/- 0.45, 41% female) from one elementary school completed the ACTIVITY on one weekday. To evaluate concurrent validity, children wore a Caltrac accelerometer and a Polar Vantage XL heart rate monitor on the day before completing the ACTIVITY. An ACTIVITY score from six time-anchored questions was obtained from the ACTIVITY. Mean Caltrac counts per minute (CNTSMIN), average activity heart rates, and cumulative minutes at or above 50% of heart rate reserve (50% HRR) were calculated for the entire day (7:00 a.m. to 7:00 p.m.). RESULTS: Significant Pearson product-moment correlations were observed between the ACTIVITY score and CNTSMIN (r = 0.40, P < 0.001) and 50% HRR (r = 0.50, P < 0.001). Answers from four of six time-anchored questions correlated significantly with heart rate scores during those time periods (r = 0.30-0.49). CONCLUSIONS: This exploratory study suggests that the ACTIVITY self-report instrument is a moderately valid instrument for measuring general activity levels of young children during the school year, including during specified periods of time. The potential for video technology to facilitate accurate physical activity recall in young children warrants further study.

Leaf O(2) uptake in the dark is independent of coincident CO(2) partial pressure.

Elevated CO(2), in the dark, is sometimes reported to inhibit leaf respiration, with respiration usually measured as CO(2) efflux. Oxygen uptake may be a better gauge of respiration because non-respiratory processes can affect dark CO(2) efflux in elevated CO(2). Two methods of quantifying O(2) uptake indicated that leaf respiration was unaffected by coincident CO(2) level in the dark.