Seasonal evolution of Aleutian low pressure systems: Implications for the North Pacific subpolar circulation

The seasonal change in the development of Aleutian low pressure systems from early fall to early winter is analyzed using a combination of meteorological reanalysis fields, satellite sea surface temperature (SST) data, and satellite wind data. The time period of the study is September–December 2002, although results are shown to be representative of the long-term climatology. Characteristics of the storms were documented as they progressed across the North Pacific, including their path, central pressure, deepening rate, and speed of translation. Clear patterns emerged. Storms tended to deepen in two distinct geographical locations—the Gulf of Alaska in early fall and the western North Pacific in late fall. In the Gulf of Alaska, a quasi-permanent “notch” in the SST distribution is argued to be of significance. The signature of the notch is imprinted in the atmosphere, resulting in a region of enhanced cyclonic potential vorticity in the lower troposphere that is conducive for storm development. Later in the season, as winter approaches and the Sea of Okhotsk becomes partially ice covered and cold, the air emanating from the Asian continent leads to enhanced baroclinicity in the region south of Kamchatka. This corresponds to enhanced storm cyclogenesis in that region. Consequently, there is a seasonal westward migration of the dominant lobe of the Aleutian low. The impact of the wind stress curl pattern resulting from these two regions of storm development on the oceanic circulation is investigated using historical hydrography. It is argued that the seasonal bimodal input of cyclonic vorticity from the wind may be partly responsible for the two distinct North Pacific subarctic gyres

Mapping coherence in measurement via full quantum tomography of a hybrid optical detector

Quantum states and measurements exhibit wave-like --- continuous, or particle-like --- discrete, character. Hybrid discrete-continuous photonic systems are key to investigating fundamental quantum phenomena, generating superpositions of macroscopic states, and form essential resources for quantum-enhanced applications, e.g. entanglement distillation and quantum computation, as well as highly efficient optical telecommunications. Realizing the full potential of these hybrid systems requires quantum-optical measurements sensitive to complementary observables such as field quadrature amplitude and photon number. However, a thorough understanding of the practical performance of an optical detector interpolating between these two regions is absent. Here, we report the implementation of full quantum detector tomography, enabling the characterization of the simultaneous wave and photon-number sensitivities of quantum-optical detectors. This yields the largest parametrization to-date in quantum tomography experiments, requiring the development of novel theoretical tools. Our results reveal the role of coherence in quantum measurements and demonstrate the tunability of hybrid quantum-optical detectors.Comment: 7 pages, 3 figure

Trials and tribulations of recruiting 2,000 older women onto a clinical trial investigating falls and fractures : vital D study

Background Randomised, placebo-controlled trials are needed to provide evidence demonstrating safe, effective interventions that reduce falls and fractures in the elderly. The quality of a clinical trial is dependent on successful recruitment of the target participant group. This paper documents the successes and failures of recruiting over 2,000 women aged at least 70 years and at higher risk of falls or fractures onto a placebo-controlled trial of six years duration. The characteristics of study participants at baseline are also described for this study.Methods The Vital D Study recruited older women identified at high risk of fracture through the use of an eligibility algorithm, adapted from identified risk factors for hip fracture. Participants were randomised to orally receive either 500,000 IU vitamin D3 (cholecalciferol) or placebo every autumn for five consecutive years. A variety of recruitment strategies were employed to attract potential participants.Results Of the 2,317 participants randomised onto the study, 74% (n = 1716/2317) were consented onto the study in the last five months of recruiting. This was largely due to the success of a targeted mail-out. Prior to this only 541 women were consented in the 18 months of recruiting. A total of 70% of all participants were recruited as a result of targeted mail-out. The response rate from the letters increased from 2 to 7% following revision of the material by a public relations company. Participant demographic or risk factor profile did not differ between those recruited by targeted mail-outs compared with other methods.Conclusion The most successful recruitment strategy was the targeted mail-out and the response rate was no higher in the local region where the study had extensive exposure through other recruiting strategies. The strategies that were labour-intensive and did not result in successful recruitment include the activities directed towards the GP medical centres. Comprehensive recruitment programs employ overlapping strategies simultaneously with ongoing assessment of recruitment rates. In our experience, and others direct mail-outs work best although rights to privacy must be respected. <br /

Improving the normalization of complex interventions: measure development based on normalization process theory (NoMAD): study protocol

&lt;b&gt;Background&lt;/b&gt; Understanding implementation processes is key to ensuring that complex interventions in healthcare are taken up in practice and thus maximize intended benefits for service provision and (ultimately) care to patients. Normalization Process Theory (NPT) provides a framework for understanding how a new intervention becomes part of normal practice. This study aims to develop and validate simple generic tools derived from NPT, to be used to improve the implementation of complex healthcare interventions.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Objectives&lt;/b&gt; The objectives of this study are to: develop a set of NPT-based measures and formatively evaluate their use for identifying implementation problems and monitoring progress; conduct preliminary evaluation of these measures across a range of interventions and contexts, and identify factors that affect this process; explore the utility of these measures for predicting outcomes; and develop an online users’ manual for the measures.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt; A combination of qualitative (workshops, item development, user feedback, cognitive interviews) and quantitative (survey) methods will be used to develop NPT measures, and test the utility of the measures in six healthcare intervention settings.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Discussion&lt;/b&gt; The measures developed in the study will be available for use by those involved in planning, implementing, and evaluating complex interventions in healthcare and have the potential to enhance the chances of their implementation, leading to sustained changes in working practices

Global perspectives on heart disease rehabilitation and secondary prevention: a scientific statement from the Association of Cardiovascular Nursing and Allied Professions, European Association of Preventive Cardiology, and International Council of Cardiovascular Prevention and Rehabilitation

Cardiovascular disease is a leading cause of death, morbidity, disability, and reduced health-related quality of life, as well as economic burden worldwide, with some 80% of disease burden occurring in the low- and middle-income country (LMIC) settings. With increasing numbers of people living longer with symptomatic disease, the effectiveness and accessibility of secondary preventative and rehabilitative health services have never been more important. Whilst LMICs experience the highest prevalence and mortality rates, the global approach to secondary prevention and cardiac rehabilitation, which mitigates this burden, has traditionally been driven from clinical guidelines emanating from high-income settings. This state-of-the art review provides a contemporary global perspective on cardiac rehabilitation and secondary prevention, contrasting the challenges of and opportunities for high vs. lower income settings. Actionable solutions to overcome system, clinician, programme, and patient level barriers to cardiac rehabilitation access in LMICs are provided

Increased somatic mutation burdens in normal human cells due to defective DNA polymerases.

Funder: Wellcome PhD StudentshipFunder: Jean Shank/Pathological Society Intermediate FellowshipFunder: Wellcome Clinical PhD fellowshipMutation accumulation in somatic cells contributes to cancer development and is proposed as a cause of aging. DNA polymerases Pol ε and Pol δ replicate DNA during cell division. However, in some cancers, defective proofreading due to acquired POLE/POLD1 exonuclease domain mutations causes markedly elevated somatic mutation burdens with distinctive mutational signatures. Germline POLE/POLD1 mutations cause familial cancer predisposition. Here, we sequenced normal tissue and tumor DNA from individuals with germline POLE/POLD1 mutations. Increased mutation burdens with characteristic mutational signatures were found in normal adult somatic cell types, during early embryogenesis and in sperm. Thus human physiology can tolerate ubiquitously elevated mutation burdens. Except for increased cancer risk, individuals with germline POLE/POLD1 mutations do not exhibit overt features of premature aging. These results do not support a model in which all features of aging are attributable to widespread cell malfunction directly resulting from somatic mutation burdens accrued during life

Telomeric expression sites are highly conserved in trypanosoma brucei

Subtelomeric regions are often under-represented in genome sequences of eukaryotes. One of the best known examples of the use of telomere proximity for adaptive purposes are the bloodstream expression sites (BESs) of the African trypanosome Trypanosoma brucei. To enhance our understanding of BES structure and function in host adaptation and immune evasion, the BES repertoire from the Lister 427 strain of T. brucei were independently tagged and sequenced. BESs are polymorphic in size and structure but reveal a surprisingly conserved architecture in the context of extensive recombination. Very small BESs do exist and many functioning BESs do not contain the full complement of expression site associated genes (ESAGs). The consequences of duplicated or missing ESAGs, including ESAG9, a newly named ESAG12, and additional variant surface glycoprotein genes (VSGs) were evaluated by functional assays after BESs were tagged with a drug-resistance gene. Phylogenetic analysis of constituent ESAG families suggests that BESs are sequence mosaics and that extensive recombination has shaped the evolution of the BES repertoire. This work opens important perspectives in understanding the molecular mechanisms of antigenic variation, a widely used strategy for immune evasion in pathogens, and telomere biology

Search for gravitational wave bursts in LIGO's third science run

We report on a search for gravitational wave bursts in data from the three LIGO interferometric detectors during their third science run. The search targets subsecond bursts in the frequency range 100-1100 Hz for which no waveform model is assumed, and has a sensitivity in terms of the root-sum-square (rss) strain amplitude of hrss ~ 10^{-20} / sqrt(Hz). No gravitational wave signals were detected in the 8 days of analyzed data.Comment: 12 pages, 6 figures. Amaldi-6 conference proceedings to be published in Classical and Quantum Gravit

Oxygen isotopic constraints on the origin and parent bodies of eucrites, diogenites, and howardites

A few eucrites have anomalous oxygen isotopic compositions. To help understand their origin and identify additional samples, we have analyzed the oxygen isotopic compositions of 18 eucrites and four diogenites. Except for five eucrites, these meteorites have ?17O values that lie within 2 of their mean value viz., -0.242±0.016', consistent with igneous isotopic homogenization of Vesta. The five exceptional eucrites–NWA 1240, Pasamonte (both clast and matrix samples), PCA 91007, A-881394, and Ibitira–have ?17O values that lie respectively 4?, 5?, 5?, 15?, and 21 away from this mean value. NWA 1240 has a ?18O value that is 5? below the mean eucrite value. Four of the five outliers are unbrecciated and unshocked basaltic eucrites, like NWA 011, the first eucrite found to have an anomalous oxygen isotopic composition. The fifth outlier, Pasamonte, is composed almost entirely of unequilibrated basaltic clasts. Published chemical data for the six eucrites with anomalous oxygen isotopic compositions (including NWA 011) exclude contamination by chondritic projectiles as a source of the oxygen anomalies. Only NWA 011 has an anomalous Fe/Mn ratio, but several anomalous eucrites have exceptional Na, Ti, or Cr concentrations. We infer that the six anomalous eucrites are probably derived from five distinct Vesta-like parent bodies (Pasamonte and PCA 91007 could come from one body). These anomalous eucrites, like many unbrecciated eucrites from Vesta, are probably deficient in brecciation and shock effects because they were sequestered in small asteroids (~10 km diameter) during the Late Heavy Bombardment following ejection from Vesta-like bodies. The preservation of Vesta's crust and the lack of deeply buried samples from the hypothesized Vesta-like bodies are consistent with the removal of these bodies from the asteroid belt by gravitational perturbations from planets and protoplanets, rather than by collisonal grinding

A treatment evaluator tool to monitor the real-world effectiveness of inhaled aztreonam lysine in cystic fibrosis

Background: Studies are required that evaluate real-world outcomes of inhaled aztreonam lysine in patients with cystic fibrosis (CF). Methods: Our treatment-evaluator tool assessed the effectiveness of inhaled aztreonam in routine practice in 117 CF patients across four time periods (6–12 (P2) and 0–6 months (P1) pre-initiation, and 0–6 (T1) and 6–12 months (T2) post-initiation). Outcomes were: changes in %-predicted forced expiratory volume in 1 s (FEV1), body-mass index (BMI), hospitalisation days and intravenous antibiotic usage. Results: Median FEV1% predicted for each 6-month period was 38.9%, 34.6%, 37.1% and 36.5%; median change was − 2.0% between P2 and P1, increasing to + 0.6% (p &lt; 0.001) between P1 and T1. Annualised hospital bed-days was reduced (p = 0.05) post-initiation, as was intravenous antibiotics days (p = 0.001). BMI increased over 6 months post-initiation (p ≤ 0.001). Conclusions: In patients with CF in routine practice, inhaled aztreonam lysine is associated with improved lung function and weight, and reduced hospitalisation and intravenous antibiotic use