Recent evidence suggests that the duration of protection by bacillus Calmette-Guérin (BCG) may exceed previous estimates with potential implications for estimating clinical and cost-efficacy.
To ...estimate the protection and duration of protection provided by BCG vaccination against tuberculosis, explore how this protection changes with time since vaccination, and examine the reasons behind the variation in protection and the rate of waning of protection.
Electronic databases including MEDLINE, Excerpta Medica Database (EMBASE), Cochrane Databases, NHS Economic Evaluation Database (NHS EED), Database of Abstracts of Reviews of Effects (DARE), Web of Knowledge, Biosciences Information Service (BIOSIS), Latin American and Caribbean Health Sciences Literature (LILACs), MEDCARIB Database, Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched from inception to May 2009. Index to Theses, System for Information on Grey Literature in Europe (SIGLE), Centre for Agricultural Bioscience International (CABI) Abstracts, Scopus, Article First, Academic Complete, Africa-Wide Information, Google Scholar, Global Health, British National Bibliography for Report Literature, and clinical trial registration websites were searched from inception to October 2009.
Electronic databases searches, screening of identified studies, data extraction and analysis were undertaken. Meta-analysis was used to present numerical and graphical summaries of clinical efficacy and efficacy by time since vaccination. Evidence of heterogeneity was assessed using the tau-squared statistic. Meta-regression allowed the investigation of observed heterogeneity. Factors investigated included BCG strain, latitude, stringency of pre-BCG vaccination tuberculin testing, age at vaccination, site of disease, study design and vulnerability to biases. Rate of waning of protection was estimated using the ratio of the measure of efficacy after 10 years compared with the efficacy in the first 10 years of a study.
Study selection. A total of 21,030 references were identified, providing data on 132 studies after abstract and full-text review. Efficacy. Protection against pulmonary tuberculosis in adults is variable, ranging from substantial protection in the UK MRC trial {rate ratio 0.22 95% confidence interval (CI) 0.16 to 0.31}, to absence of clinically important benefit, as in the large Chingleput trial rate ratio 1.05 (95% CI 0.88 to 1.25) and greater in latitudes further away from the equator. BCG vaccination efficacy was usually high, and varied little by form of disease (with higher protection against meningeal and miliary tuberculosis) or study design when BCG vaccination was given only to infants or to children after strict screening for tuberculin sensitivity. High levels of protection against death were observed from both trials and observational studies. The observed protective effect of BCG vaccination did not differ by the strain of BCG vaccine used in trials.
Reviewed studies showed that BCG vaccination protects against pulmonary and extrapulmonary tuberculosis for up to 10 years. Most studies either did not follow up participants for long enough or had very few cases after 15 years. This should not be taken to indicate an absence of effect: five studies (one trial and four observational studies) provided evidence of measurable protection at least 15 years after vaccination. Efficacy declined with time. The rate of decline was variable, with faster decline in latitudes further from the equator and in situations where BCG vaccination was given to tuberculin-sensitive participants after stringent tuberculin testing.
The main limitation of this review relates to quality of included trials, most of which were conducted before current standards for reporting were formulated. In addition, data were lacking in some areas and the review had to rely on evidence from observational studies.
BCG vaccination protection against tuberculosis varies between populations, to an extent that cannot be attributed to chance alone. Failure to exclude those already sensitised to mycobacteria and study latitude closer to the equator were associated with lower efficacy. These factors explained most of the observed variation. There is good evidence that BCG vaccination protection declines with time and that protection can last for up to 10 years. Data on protection beyond 15 years are limited; however, a small number of trials and observational studies suggest that BCG vaccination may protect for longer. Further studies are required to investigate the duration of protection by BCG vaccination.
The National Institute for Health Research Health Technology Assessment programme.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with a 382-nucleotide deletion (∆382) in the open reading frame 8 (ORF8) region of the genome have been detected in Singapore and ...other countries. We investigated the effect of this deletion on the clinical features of infection.
We retrospectively identified patients who had been screened for the ∆382 variant and recruited to the PROTECT study—a prospective observational cohort study conducted at seven public hospitals in Singapore. We collected clinical, laboratory, and radiological data from patients' electronic medical records and serial blood and respiratory samples taken during hospitalisation and after discharge. Individuals infected with the ∆382 variant were compared with those infected with wild-type SARS-CoV-2. Exact logistic regression was used to examine the association between the infection groups and the development of hypoxia requiring supplemental oxygen (an indicator of severe COVID-19, the primary endpoint). Follow-up for the study's primary endpoint is completed.
Between Jan 22 and March 21, 2020, 278 patients with PCR-confirmed SARS-CoV-2 infection were screened for the ∆382 deletion and 131 were enrolled onto the study, of whom 92 (70%) were infected with the wild-type virus, ten (8%) had a mix of wild-type and ∆382-variant viruses, and 29 (22%) had only the ∆382 variant. Development of hypoxia requiring supplemental oxygen was less frequent in the ∆382 variant group (0 0% of 29 patients) than in the wild-type only group (26 28% of 92; absolute difference 28% 95% CI 14–28). After adjusting for age and presence of comorbidities, infection with the ∆382 variant only was associated with lower odds of developing hypoxia requiring supplemental oxygen (adjusted odds ratio 0·07 95% CI 0·00–0·48) compared with infection with wild-type virus only.
The ∆382 variant of SARS-CoV-2 seems to be associated with a milder infection. The observed clinical effects of deletions in ORF8 could have implications for the development of treatments and vaccines.
National Medical Research Council Singapore.
We present the discovery by the WASP-South survey of WASP-121 b, a new remarkable short-period transiting hot Jupiter. The planet has a mass of
$1.183_{-0.062}^{+0.064}$
M
Jup, a radius of 1.865 ± ...0.044 R
Jup, and transits every
$1.274\,9255_{-0.000\,0025}^{+0.000\,0020}$
days an active F6-type main-sequence star (V = 10.4,
$1.353_{-0.079}^{+0.080}$
M⊙, 1.458 ± 0.030 R⊙, T
eff = 6460 ± 140 K). A notable property of WASP-121 b is that its orbital semimajor axis is only ∼1.15 times larger than its Roche limit, which suggests that the planet is close to tidal disruption. Furthermore, its large size and extreme irradiation (∼7.1 109 erg s−1 cm−2) make it an excellent target for atmospheric studies via secondary eclipse observations. Using the TRAnsiting Planets and PlanetesImals Small Telescope, we indeed detect its emission in the z
′-band at better than ∼4σ, the measured occultation depth being 603 ± 130 ppm. Finally, from a measurement of the Rossiter–McLaughlin effect with the CORALIE spectrograph, we infer a sky-projected spin-orbit angle of
$257{^{\circ}_{.}} 8_{-5{^{\circ}_{.}} 5}^{+5{^{\circ}_{.}} 3}$
. This result may suggest a significant misalignment between the spin axis of the host star and the orbital plane of the planet. If confirmed, this high misalignment would favour a migration of the planet involving strong dynamical events with a third body.
Bisphosphonates have been studied in randomised trials in early breast cancer to investigate their ability to prevent cancer treatment-induced bone loss (CTIBL) and reduce the risk of disease ...recurrence and metastasis. Treatment benefits have been reported but bisphosphonates do not currently have regulatory approval for either of these potential indications. This consensus paper provides a review of the evidence and offers guidance to breast cancer clinicians on the use of bisphosphonates in early breast cancer. Using the nominal group methodology for consensus, a systematic review of the literature was augmented by a workshop held in October 2014 for breast cancer and bone specialists to present and debate the available pre-clinical and clinical evidence for the use of adjuvant bisphosphonates. This was followed by a questionnaire to all members of the writing committee to identify areas of consensus. The panel recommended that bisphosphonates should be considered as part of routine clinical practice for the prevention of CTIBL in all patients with a T score of <-2.0 or ≥2 clinical risk factors for fracture. Compelling evidence from a meta-analysis of trial data of >18 000 patients supports clinically significant benefits of bisphosphonates on the development of bone metastases and breast cancer mortality in post-menopausal women or those receiving ovarian suppression therapy. Therefore, the panel recommends that bisphosphonates (either intravenous zoledronic acid or oral clodronate) are considered as part of the adjuvant breast cancer treatment in this population and the potential benefits and risks discussed with relevant patients.
Abstract
We present seven new transiting hot Jupiters from the WASP-South survey. The planets are all typical hot Jupiters orbiting stars from F4 to K0 with magnitudes of V = 10.3-12.5. The orbital ...periods are all in the range of 3.9-4.6 d, the planetary masses range from 0.4 to 2.3 M
Jup and the radii from 1.1 to 1.4 R
Jup. In line with known hot Jupiters, the planetary densities range from Jupiter-like to inflated (ρ = 0.13-1.07ρJup). We use the increasing numbers of known hot Jupiters to investigate the distribution of their orbital periods and the 3-4 d 'pile-up'.
As part of an insect resistance management plan to preserve Bt transgenic technology, annual monitoring of target pests is mandated to detect susceptibility changes to Bt toxins. Currently ...Helicoverpa zea (Boddie) monitoring involves investigating unexpected injury in Bt crop fields and collecting larvae from non-Bt host plants for laboratory diet bioassays to determine mortality responses to diagnostic concentrations of Bt toxins. To date, this monitoring approach has not detected any significant change from the known range of baseline susceptibility to Bt toxins, yet practical field-evolved resistance in H. zea populations and numerous occurrences of unexpected injury occur in Bt crops. In this study, we implemented a network of 73 sentinel sweet corn trials, spanning 16 U.S. states and 4 Canadian provinces, for monitoring changes in H. zea susceptibility to Cry and Vip3A toxins by measuring differences in ear damage and larval infestations between isogenic pairs of non-Bt and Bt hybrids over three years. This approach can monitor susceptibility changes and regional differences in other ear-feeding lepidopteran pests. Temporal changes in the field efficacy of each toxin were evidenced by comparing our current results with earlier published studies, including baseline data for each Bt trait when first commercialized. Changes in amount of ear damage showed significant increases in H. zea resistance to Cry toxins and possibly lower susceptibility to Vip3a. Our findings demonstrate that the sentinel plot approach as an in-field screen can effectively monitor phenotypic resistance and document field-evolved resistance in target pest populations, improving resistance monitoring for Bt crops.
Using the Parkes Radio Telescope, we have carried out deep observations of 11 unassociated gamma-ray sources. Periodicity searches of these data have discovered two millisecond pulsars, PSR ...J1103−5403 (1FGL J1103.9−5355) and PSR J2241−5236 (1FGL J2241.9−5236), and a long-period pulsar, PSR J1604−44 (1FGL J1604.7−4443). In addition, we searched for but did not detect any radio pulsations from six gamma-ray pulsars discovered by the Fermi satellite to a level of ∼0.04 mJy (for pulsars with a 10 per cent duty cycle).
The timing of the millisecond pulsar PSR J1103−5403 has shown that its position is 9 arcmin from the centroid of the gamma-ray source. Since these observations were carried out, independent evidence has shown that 1FGL J1103.9−5355 is associated with the flat spectrum radio source PKS 1101−536. It appears certain that the pulsar is not associated with the gamma-ray source, despite the seemingly low probability of a chance detection of a radio millisecond pulsar. We consider that PSR J1604−44 is a chance discovery of a weak, long-period pulsar and is unlikely to be associated with 1FGL J1604.7−4443. PSR J2241−5236 has a spin period of 2.2 ms and orbits a very low mass companion with a 3.5-h orbital period. The relatively high flux density and low dispersion measure of PSR J2241−5236 make it an excellent candidate for high precision timing experiments. The gamma rays of 1FGL J2241.9−5236 have a spectrum that is well modelled by a power law with an exponential cut-off, and phase binning with the radio ephemeris results in a multipeaked gamma-ray pulse profile. Observations with Chandra have identified a coincident X-ray source within 0.1 arcsec of the position of the pulsar obtained by radio timing.
We report the discoveries of three transiting exoplanets. WASP-91b is a warm Jupiter (1.34 MJup, 1.03 RJup) in a 2.8-day orbit around a metal-rich K3 star. WASP-105b is a warm Jupiter (1.8 MJup, 0.96 ...RJup) in a 7.9-day orbit around a metal-rich K2 star. WASP-107b is a warm super-Neptune/sub-Saturn (0.12 MJup, 0.94 RJup) in a 5.7-day orbit around a solar-metallicity K6 star. Considering that giant planets seem to be more common around stars of higher metallicity and stars of higher mass, it is notable that the hosts are all metal-rich, late-type stars. With orbital separations that place both WASP-105b and WASP-107b in the weak-tide regime, measurements of the alignment between the planets’ orbital axes and their stars’ spin axes may help us to understand the inward migration of short-period, giant planets. The mass of WASP-107b (2.2 MNep, 0.40 MSat) places it in the transition region between the ice giants and gas giants of the Solar System. Its radius of 0.94 RJup suggests that it is a low-mass gas giant with a H/He-dominated composition. The planet thus sets a lower limit of 2.2 MNep on the planetary mass above which large gaseous envelopes can be accreted and retained by proto-planets on their way to becoming gas giants. We may discover whether WASP-107b more closely resembles an ice giant or a gas giant by measuring its atmospheric metallicity via transmission spectroscopy, for which WASP-107b is a very good target.
We performed a genome-wide association study of 6447 bipolar disorder (BD) cases and 12 639 controls from the International Cohort Collection for Bipolar Disorder (ICCBD). Meta-analysis was performed ...with prior results from the Psychiatric Genomics Consortium Bipolar Disorder Working Group for a combined sample of 13 902 cases and 19 279 controls. We identified eight genome-wide significant, associated regions, including a novel associated region on chromosome 10 (rs10884920; P=3.28 × 10
) that includes the brain-enriched cytoskeleton protein adducin 3 (ADD3), a non-coding RNA, and a neuropeptide-specific aminopeptidase P (XPNPEP1). Our large sample size allowed us to test the heritability and genetic correlation of BD subtypes and investigate their genetic overlap with schizophrenia and major depressive disorder. We found a significant difference in heritability of the two most common forms of BD (BD I SNP-h
=0.35; BD II SNP-h
=0.25; P=0.02). The genetic correlation between BD I and BD II was 0.78, whereas the genetic correlation was 0.97 when BD cohorts containing both types were compared. In addition, we demonstrated a significantly greater load of polygenic risk alleles for schizophrenia and BD in patients with BD I compared with patients with BD II, and a greater load of schizophrenia risk alleles in patients with the bipolar type of schizoaffective disorder compared with patients with either BD I or BD II. These results point to a partial difference in the genetic architecture of BD subtypes as currently defined.
•HITRAN2016 molecular spectroscopic database is described.•Dynamic web interface at www.hitran.org is introduced.•HITRAN Application Programming Interface is introduced.•Substantial extent of the ...amount and quality of the data highlighted.•Many new spectroscopic parameters are now available in HITRAN.
This paper describes the contents of the 2016 edition of the HITRAN molecular spectroscopic compilation. The new edition replaces the previous HITRAN edition of 2012 and its updates during the intervening years. The HITRAN molecular absorption compilation is composed of five major components: the traditional line-by-line spectroscopic parameters required for high-resolution radiative-transfer codes, infrared absorption cross-sections for molecules not yet amenable to representation in a line-by-line form, collision-induced absorption data, aerosol indices of refraction, and general tables such as partition sums that apply globally to the data. The new HITRAN is greatly extended in terms of accuracy, spectral coverage, additional absorption phenomena, added line-shape formalisms, and validity. Moreover, molecules, isotopologues, and perturbing gases have been added that address the issues of atmospheres beyond the Earth. Of considerable note, experimental IR cross-sections for almost 300 additional molecules important in different areas of atmospheric science have been added to the database. The compilation can be accessed through www.hitran.org. Most of the HITRAN data have now been cast into an underlying relational database structure that offers many advantages over the long-standing sequential text-based structure. The new structure empowers the user in many ways. It enables the incorporation of an extended set of fundamental parameters per transition, sophisticated line-shape formalisms, easy user-defined output formats, and very convenient searching, filtering, and plotting of data. A powerful application programming interface making use of structured query language (SQL) features for higher-level applications of HITRAN is also provided.
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