CO2 storage and release in the deep Southern Ocean on millennial to centennial timescales.

The cause of changes in atmospheric carbon dioxide (CO2) during the recent ice ages is yet to be fully explained. Most mechanisms for glacial-interglacial CO2 change have centred on carbon exchange with the deep ocean, owing to its large size and relatively rapid exchange with the atmosphere1. The Southern Ocean is thought to have a key role in this exchange, as much of the deep ocean is ventilated to the atmosphere in this region2. However, it is difficult to reconstruct changes in deep Southern Ocean carbon storage, so few direct tests of this hypothesis have been carried out. Here we present deep-sea coral boron isotope data that track the pH-and thus the CO2 chemistry-of the deep Southern Ocean over the past forty thousand years. At sites closest to the Antarctic continental margin, and most influenced by the deep southern waters that form the ocean's lower overturning cell, we find a close relationship between ocean pH and atmospheric CO2: during intervals of low CO2, ocean pH is low, reflecting enhanced ocean carbon storage; and during intervals of rising CO2, ocean pH rises, reflecting loss of carbon from the ocean to the atmosphere. Correspondingly, at shallower sites we find rapid (millennial- to centennial-scale) decreases in pH during abrupt increases in CO2, reflecting the rapid transfer of carbon from the deep ocean to the upper ocean and atmosphere. Our findings confirm the importance of the deep Southern Ocean in ice-age CO2 change, and show that deep-ocean CO2 release can occur as a dynamic feedback to rapid climate change on centennial timescales.

Parental reactions to weight screening in young children: a randomized controlled trial.

BACKGROUND: Parental inability to recognize child overweight and physician reluctance to instigate discussion prevents behaviour change. OBJECTIVE: To evaluate parental acceptance of child overweight status following screening. METHODS: Interviewers used motivational interviewing or best practice care to discuss overweight status of 271 young children (BMI ≥ 85th ) with parents using simple traffic-light BMI charts. Follow-up sessions two weeks later (n = 251, 93%) were coded qualitatively to assess parental reactions to the information (overweight diagnosis) and how it was presented (feedback condition). RESULTS: Eight-two percent of parents rated the charts positively with few (8-10%) feeling judged. Motivational interviewing parents viewed feedback as more empathetic (relative risk, 95% CI: 4.07, 1.64-10.09), but more uncomfortable (12.2, 1.48-100.1) than best practice care parents. Overall, 65.2% of parents accepted their child was overweight, 22.1% were ambivalent and 12.7% rejected the information. Although motivational interviewing parents were less likely to accept it (OR, 95% CI: 0.49, 0.37-0.64) and more likely to be ambivalent (2.01, 1.17-3.47), the most important predictor of acceptance was a positive experience of feedback (P < 0.001). CONCLUSIONS: Simple traffic-light charts facilitate discussion of child overweight status with parents. Style of feedback is less relevant than ensuring a positive experience for parents to increase acceptance of the weight information.

Electrical and thermal transport properties of the electron-doped cuprate Sm2-x Ce x CuO4-y system.

Electrical and thermal transport measurements were performed on thin films of the electron-doped superconductor Sm2-x Ce x CuO4-y (x = 0.13 - 0.19) in order to study the evolving nature of the charge carriers from the under-doped to over-doped regime. A temperature versus cerium content (T - x) phase diagram has been constructed from the electrical transport measurements, yielding a superconducting region similar to that found for other electron-doped superconductors. Thermopower measurements show a dramatic change from the underdoped region (x < 0.15) to the overdoped region (x > 0.15). Application of the Fisher-Fisher-Huse (FFH) vortex glass scaling model to the magnetoresistance data was found to be insufficient to describe the data in the region of the vortex-solid to vortex-liquid transition. It was found instead that the modified vortex glass scaling model of Rydh, Rapp, and Anderson provided a good description of the data, indicating the importance of the applied field on the pinning landscape. A magnetic field versus temperature (H - T) phase diagram has also been constructed for the films with [Formula: see text], displaying the evolution of the vortex glass melting lines H g (T) across the superconducting regime.

A novel approach to antibiofilm susceptibility testing using a thermo-reversible matrix.

OBJECTIVE: Biofilm microorganisms are known to have a much higher tolerance to antimicrobials compared to their planktonic equivalents. Therefore, traditional antimicrobial susceptibility testing may not extrapolate to clinical treatment of infections of biofilm origin, and as a result, there is a need to not only develop antimicrobials with antibiofilm activity, but also suitable in vitro testing methods for their evaluation. In this study, we report on a novel method of antibiofilm testing using a thermo-reversible matrix (poloxamer 407), coupled with live/dead staining of bacteria cultured from the matrix. METHOD: Pseudomonas aeruginosa (NCIMB 8626) was cultured in medium containing poloxamer 407 at 37°C for 24 hours to generate biofilms. The preparation was cooled to liquefy the poloxamer and allow recovery of the biofilm cells, which were then stained with SYTO9 to determine viability following exposure to four antimicrobials: polyhexanide, octenadine dihydrochloride, povidone-iodine and silver carbonate. Over an 8-minute time period, fluorescence levels were spectrophotometrically measured and compared with bacterial controls, cultured in the absence of poloxamer and without antimicrobial. RESULTS: Untreated cells showed no reduction in viability over this period. Importantly, planktonic cells were more susceptible to test agents compared with those of a 'biofilm' phenotype cultured in poloxamer. Antibiofilm activity was evident for all of the test agents, with highest relative activity seen with octenadine dihydrochloride. CONCLUSION: In summary, a novel and relatively rapid approach to screen compounds for antibiofilm activity has been described. The method uses standard laboratory equipment and can be readily adapted to test a wide range of microorganisms and other antibiofilm compounds. DECLARATION OF INTEREST: This research was, in part, supported by Advanced Medical Solutions in the form of a Knowledge Transfer Project. Mr J. Nosworthy was employed by Advanced Medical Solutions. There are no other conflicts of interests to declare.

Intuitive eating is associated with glycaemic control in adolescents with type I diabetes mellitus.

BACKGROUND: While there have been considerable advances in the medical management of type 1 diabetes mellitus (T1DM), for many, glycaemic control remains substandard. Nutrition and eating behaviour are important additional factors to consider with regards to T1DM management and outcomes. Intuitive eating is one such factor, and has not previously been investigated in T1DM. With this in mind, we undertook a study examining the relationship between intuitive eating and glycaemic control in adolescents with T1DM. METHODS: A case-control study of adolescents with established T1DM, and age/sex matched controls was conducted. Demographic information, the Intuitive Eating Scale (IES), and HbA1c were collected. Statistical analysis was undertaken to explore associations between the IES and HbA1c as a marker of glycaemic control. RESULTS: Data on 38 adolescents with T1DM, and 39 age/sex matched controls were obtained. Those with T1DM had significantly lower (by 0.5 SD) IES scores compared to controls (p = 0.009). Higher values of both total IES and the Eating for physical rather than emotional reasons subscale were associated with lower HbA1c: HbA1c 22% lower/whole unit increase in total IES mean score, HbA1c 11% lower/whole unit increase in Eating for physical rather than emotional reasons mean score, p = 0.017 and p = 0.009 respectively. CONCLUSION: In adolescents with T1DM, there appears to be a strong association between intuitive eating, in particular the effect of emotion on eating, and glycaemic control. In addition, those with T1DM have lower scores for their intuitive eating behaviour compared to controls. Emotional eating could be a future target for screening and potentially intervening in those with T1DM, as part of a wider treatment package to improve glycaemic control. Continuing efforts are needed to fully understand the important dynamics of diabetes, adolescence, diet, emotion, and how these factors affect long term outcomes in those with T1DM.

Family CHAOS is associated with glycaemic control in children and adolescents with type 1 diabetes mellitus.

BACKGROUND: Despite advances in the medical management of type 1 diabetes mellitus (T1DM), for many, glycaemic control remains substandard. Other factors are clearly important in determining success, or lack thereof, with diabetes management. With this in mind, we have investigated whether family CHAOS may provide a novel tool to identify when environmental confusion could impact on diabetes management and subsequent glycaemic control. METHODS: A case-control study of children and adolescents with established T1DM and age-/sex-matched controls was conducted. Demographic information, both maternal and paternal CHAOS scores, and HbA1c were collected. Statistical analysis was undertaken to explore associations between T1DM and CHAOS and between CHAOS and HbA1c. RESULTS: Data on 65 children with T1DM and 60 age-/sex-matched controls were obtained. There was no evidence of group differences for maternal CHAOS (p = 0.227), but paternal CHAOS scores were higher for the T1DM group (p = 0.041). Greater maternal and paternal CHAOS scores were both associated with higher HbA1c (p ≤ 0.027). The maternal association remained after controlling for diabetes duration, SMBG frequency, and insulin therapy. CONCLUSION: In children with T1DM, there appears to be a negative association between increased environmental confusion, as rated by CHAOS, and glycaemic control. In addition, when compared to controls, fathers of children and adolescents with T1DM appear to experience CHAOS differently to mothers. These findings contribute to the growing body of literature exploring psychosocial factors in T1DM. Continuing efforts are required to fully understand how the family and psychosocial environment interact with diabetes to impact on long-term health outcomes.

A comparison of mid-forehead and axillary temperatures in newborn intensive care.

OBJECTIVE: To evaluate accuracy of mid-forehead (MFH) thermometry compared with digital axilla (DAT) temperatures in infants in newborn intensive care. STUDY DESIGN: A comparative study of MFH and DAT temperatures of newborn infants receiving tertiary-level intensive care. All admissions were considered and the following exclusion criteria applied: 'in extremis', hypoxic ischemic encephalopathy or non-English-speaking parents. Foot temperatures, infant and environmental variables were measured. RESULT: In all, 783 readings were obtained in 100 infants with a birth weight range 515 to 4885 g (mean 2152 g). The between-person correlation was 0.30 (P < 0.001) and the within-person correlation was 0.52 (P < 0.001). Bland-Altman plots showed wide 95% confidence intervals in the differences between MFH and DAT measurements (-0.87 to 1.16 °C). Differences were affected by infant variables measured. MFH more accurately predicted DAT measurements in smaller neonates and were less accurate in neonates requiring Bubble Continuous Positive Airway Pressure (CPAP). CONCLUSION: MFH thermometry is not able to replace DAT temperature recording in the newborn intensive care.

Effects of inspiratory muscle training on exercise responses in Paralympic athletes with cervical spinal cord injury.

We asked whether specific inspiratory muscle training (IMT) improves respiratory structure and function and peak exercise responses in highly trained athletes with cervical spinal cord injury (SCI). Ten Paralympic wheelchair rugby players with motor-complete SCI (C5-C7) were paired by functional classification then randomly assigned to an IMT or placebo group. Diaphragm thickness (B-mode ultrasonography), respiratory function [spirometry and maximum static inspiratory (PI ,max ) and expiratory (PE ,max ) pressures], chronic activity-related dyspnea (Baseline and Transition Dyspnea Indices), and physiological responses to incremental arm-crank exercise were assessed before and after 6 weeks of pressure threshold IMT or sham bronchodilator treatment. Compared to placebo, the IMT group showed significant increases in diaphragm thickness (P = 0.001) and PI ,max (P = 0.016). There was a significant increase in tidal volume at peak exercise in IMT vs placebo (P = 0.048) and a strong trend toward an increase in peak work rate (P = 0.081, partial eta-squared = 0.33) and peak oxygen uptake (P = 0.077, partial eta-squared = 0.34). No other indices changed post-intervention. In conclusion, IMT resulted in significant diaphragmatic hypertrophy and increased inspiratory muscle strength in highly trained athletes with cervical SCI. The strong trend, with large observed effect, toward an increase in peak aerobic performance suggests IMT may provide a useful adjunct to training in this population.

Secular changes in BMI and the associations between risk factors and BMI in children born 29 years apart.

UNLABELLED: What is already known about this subject Factors associated with children's body mass index (BMI) include parents' BMIs, birth weight, maternal smoking, sleep duration and television watching. Few studies have attempted to quantify either changes in the association between risk factors and BMI or the contribution of changes in the risk factors to increases in BMI over a generation. What this study adds The magnitude of the association between most risk factors and children's BMIs has not changed over a 29-year period. Increases in the population level of mothers' body mass index (BMI) explains ~20% of the increase in children's BMI whereas the smaller increase in fathers' BMI contributes only 6%. Maternal smoking, despite the decrease in prevalence, contributes ~17%. OBJECTIVE: Using two cohorts born 29 years apart in Dunedin, New Zealand we aim to examine changes in risk factors and their associations with body mass index (BMI) at ages 3 and 7 years, and estimate their contribution to the secular changes in BMI at age 7 years. METHODS: Birth weight and anthropometric measures at ages 3, 5 and 7 years were obtained for 974 participants in the Dunedin Multidisciplinary Health and Development Study (DMHDS), born in 1972-1973, and 241 in the Family Lifestyle, Activity, Movement and Eating Study (FLAME), born in 2001-2002. Information about maternal age, education and smoking in pregnancy, as well as breastfeeding, children's television time and time in bed, was obtained by questionnaire. RESULTS: The increase in BMI over the 29-year period was 0.84 (95% CI 0.61, 1.06) kg m(-2) at age 7. A 1-unit difference in the mother's BMI was associated with a 0.06 (0.03, 0.08) kg m(-2) difference in offspring in both studies; the 3.4 (2.8, 4.0) kg m(-2) increase in the mothers' BMIs accounts for a change of 0.19 kg m(-2) in the children's BMI. The much smaller generational increase in fathers' BMI (0.7 kg m(-2) ) correspondingly had a more limited effect on change in child BMI over time (0.06 kg m(-2) ). Although smoking in pregnancy decreased by 15% (8, 21) its association with BMI increased from 0.20 (-0.01, 0.42) in the DMHDS cohort to 1.24 (0.76, 1.71) kg m(-2) in the FLAME cohort, contributing 0.18 kg m(-2) to the increase in children's BMI. CONCLUSIONS: Societal factors such as higher maternal BMI and smoking in pregnancy contribute most to the secular increase in BMI, with changes in behavioural factors, including sleep and television viewing, having little effect in this setting.

Molecular characterisation of side population cells with cancer stem cell-like characteristics in small-cell lung cancer.

BACKGROUND: Side population (SP) fraction cells, identified by efflux of Hoechst dye, are present in virtually all normal and malignant tissues. The relationship between SP cells, drug resistance and cancer stem cells is poorly understood. Small-cell lung cancer (SCLC) is a highly aggressive human tumour with a 5-year survival rate of <10%. These features suggest enrichment in cancer stem cells. METHODS AND RESULTS: We examined several SCLC cell lines and found that they contain a consistent SP fraction that comprises <1% of the bulk population. Side population cells have higher proliferative capacity in vitro, efficient self-renewal and reduced cell surface expression of neuronal differentiation markers, CD56 and CD90, as compared with non-SP cells. Previous reports indicated that several thousand SP cells from non-small-cell lung cancer are required to form tumours in mice. In contrast, as few as 50 SP cells from H146 and H526 SCLC cell lines rapidly reconstituted tumours. Whereas non-SP cells formed fewer and slower-growing tumours, SP cells over-expressed many genes associated with cancer stem cell and drug resistance: ABCG2, FGF1, IGF1, MYC, SOX1/2, WNT1, as well as genes involved in angiogenesis, Notch and Hedgehog pathways. CONCLUSIONS: Side population cells from SCLC are highly enriched in tumourigenic cells and are characterised by a specific stem cell-associated gene expression signature. This gene signature may be used for development of targeted therapies for this rapidly fatal tumour.

Formula for the critical temperature of superconductors based on the electronic density of states and the effective mass.

A formula for the superconducting transition temperature T(c) is developed by comparing the total condensation energy contained within the coherence volume of a Cooper pair to the number of electronic states at the Fermi surface within the same coherence volume. It is found that T(c) is proportional to the ratio of the condensation energy density and normal state charge carrier density. We find that this relation holds for over 2 orders of magnitude in temperature for numerous well-known superconducting compounds belonging to distinctly different classes.

Effects of prior hypoxia exposure, endotoxin and sleep state on arousal ability to airway obstruction in piglets: implications for sudden infant death syndrome.

BACKGROUND: Respiratory tract infections may be an important component in many deaths attributed to sudden infant death syndrome (SIDS), although the mechanism of involvement remains unclear. OBJECTIVES: The hypothesis was tested that prolonged hypoxia and a thermogenic state (simulating a fever due to respiratory tract infection) would impair respiratory responsiveness to airway obstruction during sleep. METHODS: Thirty nine piglets aged 5-7 days were exposed to 24 h of moderate hypoxia and/or a low dose of endotoxin derived from Salmonella abortus equi. Responsiveness to complete and subtotal upper airway obstruction was tested during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. The end-point for airway obstruction tests was taken as the first protective response, either arousal or initiation of mouth breathing. Responsiveness was assessed as response time and response threshold (measured as respiratory effort, i.e. esophageal pressure swing). RESULTS: All animals demonstrated a thermogenic state following endotoxin delivery (drop in ear temperature of 5.8 +/- 0.2 degrees C and a small but significant increase in rectal temperature). Response time to subtotal airway obstruction was reduced during the heat conserving phase of the fever (thermogenesis; 2.8 +/- 0.5 s compared to 4.3 +/- 0.7 s during pre-endotoxin tests), but markedly increased during the recovery period (20.3 +/- 5.1 compared to 14.0 +/- 2.5 s pre-endotoxin) in NREM sleep. Response threshold was not significantly affected by either endotoxin or hypoxia in NREM sleep. Respiratory responsiveness to subtotal obstruction was markedly reduced during REM sleep (response time 40.3 +/- 10.9 s compared to 14.7 +/- 2.2 s in NREM; response threshold -14.0 +/- 1.3 mm Hg compared to -11.7 +/- 1.0 mm Hg in NREM). CONCLUSIONS: This study has demonstrated in a neonatal animal model that respiratory responsiveness to airways obstruction is delayed during recovery from fever. The findings may have implications for the human infant recovering from a respiratory illness.

Prospective incidence study of diabetes mellitus in New Zealand children aged 0 to 14 years.

AIMS/HYPOTHESIS: The aim of this study was to establish the incidence of type 1 and type 2 diabetes mellitus in children aged 0-14 years. METHODS: The New Zealand Paediatric Surveillance Unit sought monthly reporting of diabetes mellitus cases from paediatricians. All resident children aged below 15 years (1996 census risk population 832,000) who met the criteria for diagnosis of diabetes mellitus from 1 January 1999 to 31 December 2000 were included. The average annual incidence of type 1 and type 2 diabetes was calculated, as were incidence rates according to age, sex, region, ethnicity and season. Case ascertainment was estimated using hospital admission data. RESULTS: There were 315 valid reports of new cases of diabetes. Of these, 298 (94.6%) had type 1 diabetes, 12 (3.8%) had type 2 diabetes and five had other specified types of diabetes. The average annual incidence of type 1 diabetes was 17.9/100,000 (95% CI: 15.9-20/100,000). Children in the South Island had a 1.5-fold higher incidence than children in the North Island, which was largely accounted for by the variation in incidence with ethnicity, in that the European rate was 4.5 times higher than the Maori rate. The average annual incidence of type 2 diabetes was 0.84/100,000 (95% CI: 0.37-1.26/100,000). Estimated case ascertainment rate was 95.2%. CONCLUSIONS/INTERPRETATION: Type 1 diabetes incidence has doubled over the past three decades. The geographical differences previously described have persisted, and are largely explained by the ethnic variation in incidence. This population includes young adolescents with type 2 diabetes. These findings are in keeping with international trends.

Bed-sharing and the infant's thermal environment in the home setting.

AIMS: To study bed-sharing and cot-sleeping infants in the natural setting of their own home in order to identify differences in the thermal characteristics of the two sleep situations and their potential hazards. METHODS: Forty routine bed-sharing infants and 40 routine cot-sleeping infants aged 5-27 weeks were individually matched between groups for age and season. Overnight video and physiological data of bed-share infants and cot-sleeping infants were recorded in the infants' own homes including rectal, shin, and ambient temperature. RESULTS: The mean rectal temperature two hours after sleep onset for bed-share infants was 36.79 degrees C and for cot-sleeping infants, 36.75 degrees C (difference 0.05 degrees C, 95% CI -0.03 to 0.14). The rate of change thereafter was higher in the bed-share group than in the cot group (0.04 degrees C v 0.03 degrees C/h, difference 0.01, 0.00 to 0.02). Bed-share infants had a higher shin temperature at two hours (35.43 v 34.60 degrees C, difference 0.83, 0.18 to 1.49) and a higher rate of change (0.04 v -0.10 degrees C/h, difference 0.13, 0.08 to 0.19). Bed-sharing infants had more bedding. Face covering events were more common and bed-share infants woke and fed more frequently than cot infants (mean wake times/night: 4.6 v 2.5). CONCLUSIONS: Bed-share infants experience warmer thermal conditions than those of cot-sleeping infants, but are able to maintain adequate thermoregulation to maintain a normal core temperature.

Altered localization of retinoid X receptor alpha coincides with loss of retinoid responsiveness in human breast cancer MDA-MB-231 cells.

To understand the mechanism of retinoid resistance, we studied the subcellular localization and function of retinoid receptors in human breast cancer cell lines. Retinoid X receptor alpha (RXR alpha) localized throughout the nucleoplasm in retinoid-sensitive normal human mammary epithelial cells and in retinoid-responsive breast cancer cell line (MCF-7), whereas it was found in the splicing factor compartment (SFC) of the retinoid-resistant MDA-MB-231 breast cancer cell line and in human breast carcinoma tissue. In MDA-MB-231 cells, RXR alpha was not associated with active transcription site in the presence of ligand. Similarly, ligand-dependent RXR homo- or heterodimer-mediated transactivation on RXR response element or RARE showed minimal response to ligand in MDA-MB-231 cells. Infecting MDA-MB-231 cells with adenoviral RXR alpha induced nucleoplasmic overexpression of RXR alpha and resulted in apoptosis upon treatment with an RXR ligand. This suggests that nucleoplasmic RXR alpha restores retinoid sensitivity. Epitope-tagged RXR alpha and a C-terminus deletion mutant failed to localize to the SFC. Moreover, RXR alpha localization to the SFC was inhibited with RXR alpha C-terminus peptide. This peptide also induced ligand-dependent transactivation on RXRE. Therefore, the RXR alpha C terminus may play a role in the intranuclear localization of RXR alpha. Our results provide evidence that altered localization of RXR alpha to the SFC may be an important factor for the loss of retinoid responsiveness in MDA-MB-231 breast cancer cells.

Endotoxin effects on markers of autonomic nervous system function in the piglet: implications for SIDS.

The hypothesis was tested in 30 newborn piglets that the effects of a low dose of endotoxin (1 microg i.v. bolus; Salmonella abortus equi) would impair autonomic nervous system function. Two tests of autonomic function were performed following external warming (pre-endotoxin) and during endotoxin-generated thermogenesis: (1) analysis of heart rate variability in the time and frequency domains and (2) baroreflex sensitivity measured following intravenous injection of the vasoactive drugs nitroprusside and phenylephrine. Beat-to-beat heart rate variability (SDDeltaRR) fell by 2.2 ms from 7.0 ms before fever (p < 0.05). Low-frequency spectral power fell by 2.4 ms(2) from 4.1 ms(2) before fever (p < 0.05). The sensitivity of the baroreflex to changes in blood pressure induced by the vasoactive drugs decreased during fever by 0.72 ms/mm Hg for the nitroprusside test (p < 0.0005) and by 0.31 ms/mm Hg for the phenylephrine test (p < 0.005). These results indicate that in the piglet the balance of autonomic tone is altered and autonomic responsiveness reduced during the thermogenic phase of a fever. These findings are consistent with known risk factors for sudden infant death syndrome.

Respiratory responses to hypoxia/hypercapnia in small for gestational age infants influenced by maternal smoking.

AIM: To determine any variation in the respiratory responses to hypoxia/hypercapnia of infants born small for gestational age (SGA) to smoking and to non-smoking mothers. METHODS: A total of 70 average for gestational age (AGA) infants (>36 weeks gestation, >2500 g, >25th centile for gestational age, and no maternal smoking), and 47 SGA infants (<10th centile for gestational age) were studied at 1 and 3 months of age, in quiet and active sleep. Respiratory test gases were delivered through a Perspex hood to simulate face down rebreathing by slowly allowing the inspired air to be altered to a CO(2) maximum of 5% and O(2) minimum of 13.5%. The change in ventilation with inspired CO(2) was measured over 5-6 minutes of the test. The slope of a linear curve fit relating inspired CO(2) to the logarithm of ventilation was taken as a quantitative measure of ventilatory asphyxial sensitivity (VAS). RESULTS: There was no significant difference in VAS between the AGA and SGA infants (0.25 v 0.24). However within the SGA group, VAS was significantly higher (p = 0.048) in the infants whose mothers smoked during pregnancy (0.26 (0.01); n = 24) than in those that did not (0.23 (0.01); n = 23). The change in minute ventilation was significantly higher in the smokers than the non-smokers group (141% v 119%; p = 0.03) as the result of a significantly larger change in respiratory rate (8 v 4 breaths/min; p = 0.047) but not tidal volume. CONCLUSIONS: Maternal smoking appears to be the key factor in enhancing infants' respiratory responses to hypoxia/hypercapnia, irrespective of gestational age.

Are risk factors for sudden infant death syndrome different at night?

AIMS: To determine whether the risk factors for SIDS occurring at night were different from those occurring during the day. METHODS: Large, nationwide case-control study, with data for 369 cases and 1558 controls in New Zealand. RESULTS: Two thirds of SIDS deaths occurred at night (between 10 pm and 7 30 am). The odds ratio (95% CI) for prone sleep position was 3.86 (2.67 to 5.59) for deaths occurring at night and 7.25 (4.52 to 11.63) for deaths occurring during the day; the difference was significant. The odds ratio for maternal smoking for deaths occurring at night was 2.28 (1.52 to 3.42) and that for the day 1.27 (0.79 to 2.03); that for the mother being single was 2.69 (1.29 to 3.99) for a night time death and 1.25 (0.76 to 2.04) for a daytime death. Both interactions were significant. The interactions between time of death and bed sharing, not sleeping in a cot or bassinet, Maori ethnicity, late timing of antenatal care, binge drinking, cannabis use, and illness in the baby were also significant, or almost so. All were more strongly associated with SIDS occurring at night. CONCLUSIONS: Prone sleep position was more strongly associated with SIDS occurring during the day, whereas night time deaths were more strongly associated with maternal smoking and measures of social deprivation.

Prone versus supine sleep position: a review of the physiological studies in SIDS research.

A number of physiological studies, published over the last 10 years, have investigated the links between prone sleeping and sudden infant death syndrome (SIDS). This review evaluates those studies and derives an overview of the different affects of sleeping prone or supine in infancy. Generally, compared with the supine, the prone position raises arousal and wakening thresholds, promotes sleep and reduces autonomic activity through decreased parasympathetic activity, decreased sympathetic activity or an imbalance between the two systems. In addition, resting ventilation and ventilatory drive is improved in preterm infants, but in older infants (>1 month), there is no improvement in ventilation, and in 3-month-old infants, the position is adverse in terms of poorer ventilatory drive (in active sleep only). The majority of findings suggest a reduction in physiological control related to respiratory, cardiovascular and autonomic control mechanisms, including arousal during sleep in the prone position. Since the majority of these findings are from studies of healthy infants, continued reinforcement of the supine sleep recommendations for all infants is emphasized.

Persistent preswitch clonotypic myeloma cells correlate with decreased survival: evidence for isotype switching within the myeloma clone.

Multiple myeloma (MM) is identified by unique immunoglobulin heavy chain (IgH) variable diversity joining region gene rearrangements, termed clonotypic, and an M protein termed the "clinical" isotype. Transcripts encoding clonotypic pre and postswitch IgH isotypes were identified in MM peripheral blood mononuclear cells (PBMCs), bone marrow (BM), and mobilized blood. For 29 patients, 38 BM, 17 mobilized blood, and 334 sequential PBMC samples were analyzed at diagnosis, before and after transplantation for 2 to 107 months. The clinical clonotypic isotype was readily detectable and persisted throughout treatment. Eighty-two percent of BM and 38% of PBMC samples also expressed nonclinical clonotypic isotypes. Clonotypic immunoglobulin M (IgM) was detectable in 68% of BM and 25% of PBMC samples. Nonclinical clonotypic isotypes were detected in 41% of mobilized blood samples, but clonotypic IgM was detected in only 12%. Patients with persistent clonotypic IgM expression had adverse prognostic features at diagnosis (lower hemoglobin, higher beta(2)-microglobulin) and higher numbers of BM plasma cells compared with patients with infrequent/absent clonotypic IgM. Patients with persistent clonotypic IgM expression had significantly poorer survival than patients with infrequent IgM expression (P <.0001). In a multivariate analysis, persistent clonotypic IgM expression in the blood correlated independently with poor survival (P =.01). In nonobese diabetic severe combined immunodeficiency mice, xenografted MM cells expressed clinical and nonclinical postswitch clonotypic isotypes. MM expressing clonotypic IgM engrafted both primary and secondary mice, indicating their persistence within the murine BM. This study demonstrates that MM clonotypic cells expressing preswitch transcripts are tied to disease burden and outcomes. Because MM pathology involves postswitch plasma cells, this raises the possibility that IgH isotype switching in MM may accompany worsening disease.