Household air pollution and COPD: cause and effect or confounding by other aspects of poverty?

SETTING: Household air pollution (HAP) and chronic obstructive pulmonary disease (COPD) are both major public health problems, reported to cause around 4 million and 3 million deaths every year, respectively. The great majority of these deaths, as well as the burden of disease during life is felt by people in low- and middle-income countries (LMICs).OBJECTIVE and DESIGN: The extent to which HAP causes COPD is controversial; we therefore undertook this review to offer a viewpoint on this from the Global Initiative for COPD (GOLD).RESULTS: We find that while COPD is well-defined in many studies on COPD and HAP, there are major limitations to the definition and measurement of HAP. It is thus difficult to disentangle HAP from other features of poverty that are themselves associated with COPD. We identify other limitations to primary research studies, including the use of cross-sectional designs that limit causal inference.CONCLUSION: There is substantial preventable morbidity and mortality associated with HAP, COPD and poverty, separately and together. Although it may not be possible to define clear causal links between HAP and COPD, there is a clear urgency to reduce the avoidable burden of disease these inflict on the world´s poor.

Chip-based quantum key distribution.

Improvement in secure transmission of information is an urgent need for governments, corporations and individuals. Quantum key distribution (QKD) promises security based on the laws of physics and has rapidly grown from proof-of-concept to robust demonstrations and deployment of commercial systems. Despite these advances, QKD has not been widely adopted, and large-scale deployment will likely require chip-based devices for improved performance, miniaturization and enhanced functionality. Here we report low error rate, GHz clocked QKD operation of an indium phosphide transmitter chip and a silicon oxynitride receiver chip-monolithically integrated devices using components and manufacturing processes from the telecommunications industry. We use the reconfigurability of these devices to demonstrate three prominent QKD protocols-BB84, Coherent One Way and Differential Phase Shift-with performance comparable to state-of-the-art. These devices, when combined with integrated single photon detectors, pave the way for successfully integrating QKD into future telecommunications networks.

Photon pair generation in a silicon micro-ring resonator with reverse bias enhancement.

Photon sources are fundamental components for any quantum photonic technology. The ability to generate high count-rate and low-noise correlated photon pairs via spontaneous parametric down-conversion using bulk crystals has been the cornerstone of modern quantum optics. However, future practical quantum technologies will require a scalable integration approach, and waveguide-based photon sources with high-count rate and low-noise characteristics will be an essential part of chip-based quantum technologies. Here, we demonstrate photon pair generation through spontaneous four-wave mixing in a silicon micro-ring resonator, reporting separately a maximum coincidence-to-accidental (CAR) ratio of 602 ± 37 (for a generation rate of 827kHz), and a maximum photon pair generation rate of 123 MHz ± 11 kHz (with a CAR value of 37). To overcome free-carrier related performance degradations we have investigated reverse biased p-i-n structures, demonstrating an improvement in the pair generation rate by a factor of up to 2 with negligible impact on CAR.

A superconducting nanowire single photon detector on lithium niobate.

Superconducting nanowire single photon detectors (SNSPDs) are a key enabling technology for optical quantum information science. In this paper we demonstrate a SNSPD fabricated on lithium niobate, an important material for high speed integrated photonic circuits. We report a system detection efficiency of 0.15% at a 1 kHz dark count rate with a maximum of ~1% close to the critical current at 1550 nm wavelength for a parallel wire SNSPD with front side illumination. There is clear scope for improving on this performance with further materials optimization. Detector integration with a lithium niobate optical waveguide is simulated, demonstrating the potential for high single photon detection efficiency in an integrated quantum optic circuit.

Trends in obstetric practices and meconium aspiration syndrome: a population-based study.

OBJECTIVE: To determine trends in the incidence of meconium aspiration syndrome (MAS), and maternal factors and obstetric practices associated with any decline. DESIGN: Population-based cohort study. SETTING: New South Wales (NSW), Australia. POPULATION: All 877 037 liveborn, singleton, term infants (≥ 37 weeks of gestation) in the period 1997-2007. METHODS: Data were obtained from birth records linked to the neonatal hospital discharge records. The birth data provided information on maternal and obstetric factors, whereas the outcome of interest, MAS, was obtained from hospital data on the neonates. Multivariable logistic regression was used to estimate the risk of MAS while simultaneously adjusting for the explanatory variables. MAIN OUTCOME MEASURES: The incidence of MAS per 1000 births, and odds ratios and 95% confidence intervals for maternal and obstetric factors for the development of MAS. RESULTS: The incidence of MAS declined significantly by 11.3% per annum (95% CI 10.1-12.6; P < 0.001) from 4.1 per 1000 births in 1997 to 1.3 per 1000 births in 2007. This was associated with a statistically significant decline in risk factors: maternal smoking (from 20 to 12%), gestational age (from 57 to 47% ≥ 40 weeks of gestation), delivery at small hospitals (from 15 to 9%) and infants with birthweight below the third percentile (from 3.3 to 2.4%). There were simultaneous statistically significant increases in practices that reduce the risk of MAS: labour inductions (from 22 to 27%) and birth by caesarean section, both elective, prior to 40 weeks of gestation (from 7.3 to 13.8%), and emergency (from 3.0 to 5.3% prior to 40 weeks of gestation, and from 5.1 to 6.7% at 40 weeks of gestation or later). CONCLUSIONS: The rate of MAS is declining, and this decline is associated with a reduction in maternal and pregnancy risk factors, and an increase in protective obstetric practices.

Long-distance entanglement-based quantum key distribution over optical fiber.

We report the first entanglement-based quantum key distribution (QKD) experiment over a 100-km optical fiber. We used superconducting single photon detectors based on NbN nanowires that provide high-speed single photon detection for the 1.5-mum telecom band, an efficient entangled photon pair source that consists of a fiber coupled periodically poled lithium niobate waveguide and ultra low loss filters, and planar lightwave circuit Mach-Zehnder interferometers (MZIs) with ultra stable operation. These characteristics enabled us to perform an entanglement-based QKD experiment over a 100-km optical fiber. In the experiment, which lasted approximately 8 hours, we successfully generated a 16 kbit sifted key with a quantum bit error rate of 6.9 % at a rate of 0.59 bits per second, from which we were able to distill a 3.9 kbit secure key.

Late deaths in multiple trauma patients receiving intensive care.

We reviewed the cause and timing of death of all the patients who died within hospital following multiple trauma and admission to a multidisciplinary intensive care unit (ICU) that also acts as a tertiary referral centre for neurosurgery. The ICU database identified 101 such patients in a 3-year period and their records were reviewed retrospectively. There were 40 (39%) deaths within 24 h of admission to the ICU, 38 of which resulted from severe brain injury and two from haemorrhagic shock (HS). A further 61 (60%) deaths occurred more than 24 h after the time of admission to ICU (mean 7 days; range 2-49 days), of which 46 (75%) were due to severe brain injury. While these findings do not question the promulgated tri-modal distribution of death following trauma, they are at variance with the view that the third peak of deaths is due mainly to multiple organ failure. When severe head injury accompanies multiple trauma, it is likely to be the major determinant of late mortality. If outcome from major trauma is to be improved, then a greater emphasis needs to be placed on the prevention and optimal management of severe brain injury.

Linkage and association studies of the relationship between endometriosis and genes encoding the detoxification enzymes GSTM1, GSTT1 and CYP1A1.

An association between endometriosis and the glutathione S-transferase (GST) M1 null mutation has been reported in French and Slavic populations. We aimed to replicate this association of endometriosis in a UK population, and to test for association with the GSTT1 null mutation or the cytochrome P450 (CYP) 1A1 MspI polymorphism. We genotyped 148 women each with endometriosis (sporadic cases, n = 91; familial cases, n = 57), a population control of 95 male blood donors, and a control group of 53 women with a normal pelvis at hysterectomy. No significant differences were found between cases and controls in the frequencies of the GSTM1 and GSTT1 null mutations, or the CYP1A1 MspI polymorphism. However, the combination of the GSTM1 null genotype and the CYP1A1 MspI polymorphism was associated with a small increased risk of endometriosis, and this warrants further investigation. We also tested for linkage to the chromosome 1p13 region, to which GSTM1 has been mapped, in 52 sister-pairs with stage III-IV disease using three highly polymorphic microsatellite markers. However, there was no evidence of linkage, suggesting that this region may not be implicated in disease susceptibility.

Association between endometriosis and N-acetyl transferase 2 polymorphisms in a UK population.

The relationship between endometriosis and polymorphisms in the N-acetyl transferase 2 (NAT 2) gene was investigated in a UK population, as this gene has been previously implicated in the aetiology of the disease. Point mutations in the gene result in the variant alleles NAT 2 *5, *6 and *7 from the wild-type NAT 2 *4 allele. Homozygotes for the NAT 2 *4 wild type allele are fast NAT acetylators, while heterozygotes with one wild-type allele and a variant NAT 2 *5, *6 or *7 allele have reduced enzyme activity, and individuals with two variant alleles are slow acetylators. The NAT 2 *4/*6 genotype was significantly more common among affected women (35.2%) than population controls (8.1%; P = 0.0001) or unaffected women (4.2%; P = 0.02). Significantly more affected women (57.4%) were fast acetylators than were population controls (32.3%; P < 0.01) or unaffected women (33.3%; P < 0.05). These data suggest that altered NAT 2 enzyme activity may be a predisposition factor in endometriosis, or that NAT 2 alleles may be in linkage disequilibrium with a susceptibility allele in the same chromosomal region.

Toward developing a genome-wide microsatellite marker set for linkage analysis in the rhesus macaque (Macaca mulatta): identification of 76 polymorphic markers.

Linkage analysis can be problematic in humans because of the lack of large, multigenerational pedigrees and the difficulties in obtaining phenotypic data on all family members. In contrast, large, captive colonies of rhesus macaque are a potentially valuable resource for linkage studies because detailed phenotypic and genealogical data are kept, inbreeding is avoided, and DNA samples can usually be obtained. Microsatellite marker sets for genome-wide screening are available in a number of species, but not for the rhesus macaque. We tested primers to 400 human microsatellite markers from a genome-wide mapping set using DNA from nine unrelated female rhesus macaques. We found that 76 (19%) of the primers amplified a polymorphic product using the standard protocols for human DNA. The average heterozygosity of the markers in humans was 0.80, compared to 0.65 in the rhesus macaques. This study provides preliminary data, which could be used toward the development of a linkage mapping set in this species. There would be a need, however, to confirm the Mendelian inheritance of the markers.

Absence of a relationship between endometriosis and the N314D polymorphism of galactose-1-phosphate uridyl transferase in a UK population.

An association between the N314D polymorphism of galactose-1-phosphate uridyl transferase and endometriosis has recently been reported in a North American population. To determine whether such an association exists in the UK population, we genotyped 148 women with sporadic (n = 91) or familial (n = 57) endometriosis, a control population of 95 male blood donors and a control group of 53 women with a normal pelvis at hysterectomy. Heterozygosity for the polymorphism was found in 14.9% (22/148) of affected women, 13.7% (13/95) of male blood donors and 11.3% (6/53) of women with a normal pelvis. There was no statistically significant difference in the frequency of the polymorphism between cases and controls in the UK population, even when the cases were divided into groups of moderate-severe disease, sporadic cases or familial cases. We conclude that the galactose-1-phosphate uridyl transferase N314D polymorphism is unlikely to be associated with endometriosis in the UK population.

The natural history of fetomaternal alloimmunization to the platelet-specific antigen HPA-1a (PlA1, Zwa) as determined by antenatal screening.

Immunization against the human platelet antigen (HPA)-1 alloantigen is the most common cause of severe fetal and neonatal thrombocytopenia. Fetal therapy has substantial risks and its indications need better definition. Of 24,417 consecutive pregnant women, 618 (2.5%) were HPA-1a negative of whom 385 entered an observational study. All were HLA-DRB3*0101 genotyped and screened for anti-HPA-1a. Their partners and neonates were HPA-1 genotyped and the latter were assessed by cord blood platelet counts and cerebral ultrasound scans. Anti-HPA-1a was detected in 46 of 387 pregnancies (12.0%; 95% CI 8.7%-15.2%). All but one were HLA-DRB3*0101 positive (odds ratio 140; 95% CI 19-1035; P< .00001). One baby died in utero, and of 26 HPA-1a-positive babies born to women with persistent antenatal antibodies, 9 were severely thrombocytopenic (8 with a count <10 x 10(9)/L, 1 with a large porencephalic cyst), 10 were mildly thrombocytopenic, whereas 7 had normal platelet counts. Severe thrombocytopenia was significantly associated with a third trimester anti-HPA-1a titer >/= 1:32 (P = . 004), but was not observed in babies of women with either transient or postnatal-only antibodies. HPA-1a alloimmunization complicates 1 in 350 unselected pregnancies, resulting in severe thrombocytopenia in 1:1,200. HPA-1a and HLA-DRB3*0101 typing combined with anti-HPA-1a titration allows selection of the majority of pregnancies at risk of severe thrombocytopenia.

Endometriosis in monozygotic twins.

OBJECTIVE: To describe the occurrence of endometriosis in monozygotic twins. DESIGN: Postal questionnaire plus confirmation of disease status. SETTING: Twins were recruited via the American Endometriosis Association and the National Endometriosis Society of Great Britain and via British gynecologists. RESULT(S): Fourteen twin pairs were concordant for endometriosis, and two were discordant. Nine pairs of twins had moderate-severe endometriosis. CONCLUSION(S): These findings contribute to the growing body of literature that suggests endometriosis has a genetic basis.

Risk factors for endometriosis in the rhesus monkey (Macaca mulatta): a case-control study.

The autopsy records between 1980 and 1995 of 399 female rhesus monkeys (Macaca mulatta) at the Wisconsin Regional Primate Research Center were examined. Spontaneous endometriosis was found in 81 (20%) of the animals. The mean (+/- SD) ages at death for animals with and without endometriosis were 20.7 +/- 5.5 (range 10-35) and 13.4 +/- 7.7 (range 4-37) years respectively. Many of the animals had been exposed to experimental procedures, including laparoscopies, hysterotomies and oestradiol implants, and these were examined as possible risk factors for endometriosis. Of the 81 affected animals, 62 were matched to unaffected controls for age at death (to within 1 year) and year of death (to within 2 years) and the effect of various factors on the development of endometriosis was determined using conditional logistic regression. Exposure to three or more oestradiol implants or one or more hysterotomies were both significant risk factors, with estimated relative risks of 9.7 (95% confidence interval 2.5-37.2) and 5.8 (95% confidence interval 1.6-20.2) respectively. Animals that had been exposed to one or more laparoscopies showed no increased risk for developing endometriosis. These findings provide insight into the aetiology of the disease in women. ?2P51 4RR00167