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New drugs to target different pathways in pulmonary hypertension has resulted in increased combination therapy, but details of this use in infants are not well described. In this large multicenter database study, we describe the pharmacoepidemiology of combination pulmonary vasodilator therapy in critically ill infants.
Methods:
We identified inborn infants discharged home from a Pediatrix neonatal ICU from 1997 to 2020 exposed to inhaled nitric oxide, sildenafil, epoprostenol, or bosentan for greater than two consecutive days. We compared clinical variables and drug utilisation between infants receiving simultaneous combination and monotherapy. We reported each combination’s frequency, timing, and duration and graphically represented drug use over time.
Results:
Of the 7681 infants that met inclusion criteria, 664 (9%) received combination therapy. These infants had a lower median gestational age and birth weight, were more likely to have cardiac and pulmonary anomalies, receive cardiorespiratory support, and had higher in-hospital mortality than those receiving monotherapy. Inhaled nitric oxide and sildenafil were most frequently used, and utilisation of combination and monotherapy for all drugs increased over time. Inhaled nitric oxide and epoprostenol were used in infants with a higher gestational age, earlier postnatal age, and shorter duration than sildenafil and bosentan. Dual therapy with inhaled nitric oxide and sildenafil was the most common combination therapy.
Conclusion:
Our study revealed an increased use of combination pulmonary vasodilator therapy, favouring inhaled nitric oxide and sildenafil, yet with considerable practice variation. Further research is needed to determine the optimal combination, sequence, dosing, and disease-specific indications for combination therapy.
Clostridioides difficile infection (CDI) may be misdiagnosed if testing is performed in the absence of signs or symptoms of disease. This study sought to support appropriate testing by estimating the impact of signs, symptoms, and healthcare exposures on pre-test likelihood of CDI.
Methods:
A panel of fifteen experts in infectious diseases participated in a modified UCLA/RAND Delphi study to estimate likelihood of CDI. Consensus, defined as agreement by >70% of panelists, was assessed via a REDCap survey. Items without consensus were discussed in a virtual meeting followed by a second survey.
Results:
All fifteen panelists completed both surveys (100% response rate). In the initial survey, consensus was present on 6 of 15 (40%) items related to risk of CDI. After panel discussion and clarification of questions, consensus (>70% agreement) was reached on all remaining items in the second survey. Antibiotics were identified as the primary risk factor for CDI and grouped into three categories: high-risk (likelihood ratio [LR] 7, 93% agreement among panelists in first survey), low-risk (LR 3, 87% agreement in first survey), and minimal-risk (LR 1, 71% agreement in first survey). Other major factors included new or unexplained severe diarrhea (e.g., ≥ 10 liquid bowel movements per day; LR 5, 100% agreement in second survey) and severe immunosuppression (LR 5, 87% agreement in second survey).
Conclusion:
Infectious disease experts concurred on the importance of signs, symptoms, and healthcare exposures for diagnosing CDI. The resulting risk estimates can be used by clinicians to optimize CDI testing and treatment.
The Pediatric and Congenital Electrophysiology Society (PACES) is a global organisation committed to the care of children and adults with CHD and arrhythmias.
Objective:
To evaluate the global needs and potential inequities as it relates to cardiac implantable electronic devices.
Methods:
ARROW (Assessment of Rhythm Resources arOund the World) is an online survey about cardiac implantable electronic devices, sent electronically to physicians within the field of Cardiology, Pediatric Cardiology, Electrophysiology and Pediatric Electrophysiology.
Results:
ARROW received 42 responders from 28 countries, 50% from low-/middle-income regions. The main differences between low-/middle- and high-income regions include availability of expertise on paediatric electrophysiology (50% versus 93%, p < 00.5) and possibility to perform invasive procedures (35% versus 93%, p < 0.005). Implant of devices in low-income areas relies significantly on patient’s resources (71%). The follow-up of the devices is on the hands of paediatric cardiologist/electrophysiologist in higher resources centres (93% versus 50%, p < 0.05).
Conclusions:
The ARROW survey represents an initial assessment of the geographical characteristics in the field of Pediatric Electrophysiology. The next step is to make this “state of the art” more extensive to other aspects of the expertise. The relevance of collecting this data before the World Congress of Pediatric Cardiology and Cardiac Surgery (WCPCCS) in 2023 in Washington DC was emphasised in order to share the resulting information with the international community and set a plan of action to assist the development of arrhythmia services for children within developing regions of the world.
Increasingly, parents in separated families equally share care of their children post-separation. In this article we extend a well-known family policy model to generate hypotheses about the level of child support to be paid by separated parents when children live primarily with their mother (‘sole custody’) in contrast to when children spend equal time with both parents (‘shared care’). We test these hypotheses with data collected from thirteen countries. In sole custody cases, countries with an earner-carer policy model do have lower child support expectations than countries with a traditional family policy model or a market-oriented model, as predicted. Countries with a traditional family policy model do have the highest orders in the shared case, as predicted. However, there is as much variation within models as there is between, suggesting new analytic frameworks for considering child support in family policy need to be developed.
To explore the relationship between cannabis use and self-report dimensions of psychosis in a population of university students presenting for any reason to primary care.
Method
One thousand and forty-nine students attending the Student Health Unit, National University of Ireland, Galway, completed self-report questionnaires on alcohol and substance misuse, non-clinical dimensions of psychosis (Community Assessmemnt of Psychic Experiences), anxiety and depression (Hospital Anxiety and Depression Scale). Association of cannabis use with psychiatric symptoms was explored whilst controlling for confounds.
Results
More frequent cannabis use was independently associated with greater intensity of positive, negative and depressive psychotic symptoms. The earlier the age of onset of cannabis use, the more positive psychotic symptoms were reported.
Conclusion
These findings support the hypothesis that cannabis use increases the risk of developing psychotic symptoms and that this risk is further increased in those individuals who use cannabis more heavily and commence it at a younger age.
We consider peeling of an elastic sheet away from an elastic substrate through propagation of a fluid-filled crack along the interface between the two. The peeling is driven by a bending moment applied to the sheet and is resisted by viscous flow towards the crack tip and by the toughness of any bonding between the sheet and the substrate. Travelling-wave solutions are determined using lubrication theory coupled to the full equations of elasticity and fracture. The propagation speed $v$ scales like $M^{3}/\unicode[STIX]{x1D707}\bar{E}^{2}d^{5}=Bd\unicode[STIX]{x1D705}^{3}/144\unicode[STIX]{x1D707}$, where $d$ is the sheet’s thickness, $B=\bar{E}d^{3}/12$ its stiffness, $\bar{E}=E/(1-\unicode[STIX]{x1D708}^{2})$ its plane-strain modulus, $\unicode[STIX]{x1D707}$ the fluid viscosity, $M$ the applied bending moment and $\unicode[STIX]{x1D705}=M/B$ the sheet’s curvature due to bending; and the prefactor depends on the dimensionless toughness. If the toughness is small then there is a region of dry shear failure ahead of the fluid-filled region. The expressions for the propagation speed have been used to derive new similarity solutions for the spread of an axisymmetric fluid-filled blister in a variety of regimes: constant-flux injection resisted by elastohydrodynamics in the tip leads to spread proportional to $t^{4/13}$, $t^{4/17}$ and $t^{7/19}$ for peeling-by-bending, gravitational spreading and peeling-by-pulling, respectively.
Cancer-related fatigue (CRF) is one of the most commonly reported disease- and treatment-related side effects that impede quality of life. This systematic review and meta-analysis describes the effects of nutrition therapy on CRF and quality of life in people with cancer and cancer survivors. Studies were identified from four electronic databases until September 2017. Eligibility criteria included randomised trials in cancer patients and survivors; any structured dietary intervention describing quantities, proportions, varieties and frequencies of food groups or energy and macronutrient consumption targets; and measures of CRF and quality of life. Standardised mean differences (SMD) were pooled using random-effects models. The American Dietetic Association’s Evidence Analysis Library Quality Checklist for Primary Research was used to evaluate the methodological quality and risk of bias. A total of sixteen papers, of fifteen interventions, were included, comprising 1290 participants. Nutrition therapy offered no definitive effect on CRF (SMD 0·18 (95 % CI –0·02, 0·39)) or quality of life (SMD 0·07 (95 % CI –0·10, 0·24)). Preliminary evidence indicates plant-based dietary pattern nutrition therapy may benefit CRF (SMD 0·62 (95 % CI 0·10, 1·15)). Interventions using the patient-generated subjective global assessment tool and prescribing hypermetabolic energy and protein requirements may improve quality of life. However, the heterogeneity seen in study design, nutrition therapies, quality-of-life measures and cancer types impede definitive dietary recommendations to improve quality of life for cancer patients. There is insufficient evidence to determine the optimal nutrition care plan to improve CRF and/or quality of life in cancer patients and survivors.
The technique of neutron inelastic scattering has demonstrated the presence of longitudinal acoustic phonons in two layer-silicate minerals. Values of the elastic constants determined from the dispersion curves have established the validity of the technique for this class of materials.
In most developed countries, children in lone parent families face a high risk of poverty. A partial solution commonly sought in English-speaking nations is to increase the amounts of private child maintenance paid by the other parent. However, where lone parent families are in receipt of social assistance benefits, some countries hold back a portion of the child maintenance to reduce public expenditures. This partial ‘pass-through’ treats child maintenance as a substitute for cash benefits which conceivably neutralises its poverty reduction potential. Such neutralising effects are not well understood and can be obscured further when more subtle interactions between child maintenance systems and social security systems operate. This research makes a unique contribution to knowledge by exposing the hidden interaction effects operating in similar child maintenance systems across four countries: the United Kingdom, United States (Wisconsin), Australia and New Zealand. We found that when child maintenance is counted as income in calculating benefit entitlements, it can reduce the value of cash benefits. Using model lone parent families with ten different employment and income scenarios, we show how the poverty reduction potential of child maintenance is affected by whether it is treated as a substitute for, or a complement to, cash benefits.
Reservoir age offsets are widely used to correct marine and speleothem radiocarbon age measurements for various calibration purposes. They also serve as a powerful tracer for carbon cycle dynamics. However, a clear terminology regarding reservoir age offsets is lacking, sometimes leading to miscalculations. This note seeks to provide consistent conventions for reporting reservoir 14C disequilibria useful to a broad range of environmental sciences. This contribution introduces the F14R and δ14R metrics to express the relative 14C disequilibrium between two contemporaneous reservoirs and the R metric as the associated reservoir age offset.
A new radiocarbon preparation facility was set up in 2010 at the Godwin Laboratory for Palaeoclimate Research, at the University of Cambridge. Samples are graphitized via hydrogen reduction on an iron powder catalyst before being sent to the Chrono Centre, Belfast, or the Australian National University for accelerator mass spectrometry (AMS) analysis. The experimental setup and procedure have recently been developed to investigate the potential for running small samples of foraminiferal carbonate. By analyzing background values of samples ranging from 0.04 to 0.6 mg C along with similar sized secondary standards, the setup and experimental procedures were optimized for small samples. “Background” modern 14C contamination has been minimized through careful selection of iron powder, and graphitization has been optimized through the use of “small volume” reactors, allowing samples containing as little as 0.08 mg C to be graphitized and accurately dated. Graphitization efficiency/fractionation is found not to be the main limitation on the analysis of samples smaller than 0.07 mg C, which rather depends primarily on AMS ion beam optics, suggesting further improvements in small sample analysis might yet be achieved with our methodology.
Methylation of the fragile X mental retardation 1 (FMR1) exon 1/intron 1 boundary positioned fragile X related epigenetic element 2 (FREE2), reveals skewed X-chromosome inactivation (XCI) in fragile X syndrome full mutation (FM: CGG > 200) females. XCI skewing has been also linked to abnormal X-linked gene expression with the broader clinical impact for sex chromosome aneuploidies (SCAs). In this study, 10 FREE2 CpG sites were targeted using methylation specific quantitative melt analysis (MS-QMA), including 3 sites that could not be analysed with previously used EpiTYPER system. The method was applied for detection of skewed XCI in FM females and in different types of SCA. We tested venous blood and saliva DNA collected from 107 controls (CGG < 40), and 148 FM and 90 SCA individuals. MS-QMA identified: (i) most SCAs if combined with a Y chromosome test; (ii) locus-specific XCI skewing towards the hypomethylated state in FM females; and (iii) skewed XCI towards the hypermethylated state in SCA with 3 or more X chromosomes, and in 5% of the 47,XXY individuals. MS-QMA output also showed significant correlation with the EpiTYPER reference method in FM males and females (P < 0.0001) and SCAs (P < 0.05). In conclusion, we demonstrate use of MS-QMA to quantify skewed XCI in two applications with diagnostic utility.
The intent of the paper is to develop the service marketing logic (S-D logic) strategy that is centered on service as a means to differentiate global strategy from those of competitors. The context of the paper is to examine S-D logic in global supply chains.
Design/Methodology:
The paper is a theory driven conceptual piece.
Findings:
Globalization emphasizes complex interconnected systems, while S-D logic emphasizes the importance of leveraging operant resources in order to achieve sustainable competitive advantage. Both S-D logic and globalization apply in the supply chain context. This paper focuses on the global supply chain and the importance of leveraging service based operant resources. Because the focus of management has shifted from a domestic to a more complex, three-dimensional network, it is critical for practitioners and researchers to understand how to optimize service based operant resources in the global marketplace.
Practical Implications:
Because the focus of management has shifted from a domestic to a more complex, three-dimensional global network, it is critical for practitioners and researchers to understand how to optimize service based operant resources in the global marketplace. We suggest that in this dynamic marketplace, both globalization and S-D logic are required to fully explain supply chain performance. Specifically, we suggest that managers develop a global ‘supply-chain management’ perspective allowing for the key operant resource – human capital – to create synergistic partner relationships and customer experiences resulting in superior performance.
Originality/Value:
This is one of the first (if not the first) paper that examines S-D logic in a global context. This move forward from the domestic orientation of many/most of the recent literature provides the foundation for future global research into the S-D logic.
Drugs that kill or inhibit the sexual stages of Plasmodium in order to prevent transmission are important components of malaria control programmes. Reducing gametocyte carriage is central to the control of Plasmodium falciparum transmission as infection can result in extended periods of gametocytaemia. Unfortunately the number of drugs with activity against gametocytes is limited. Primaquine is currently the only licensed drug with activity against the sexual stages of malaria parasites and its use is hampered by safety concerns. This shortcoming is likely the result of the technical challenges associated with gametocyte studies together with the focus of previous drug discovery campaigns on asexual parasite stages. However recent emphasis on malaria eradication has resulted in an upsurge of interest in identifying compounds with activity against gametocytes. This review examines the gametocytocidal properties of currently available drugs as well as those in the development pipeline and examines the prospects for discovery of new anti-gametocyte compounds.
For some while there has been a growing awareness from both internal and external stakeholders that the governance and risk management in United Kingdom (U.K.) insurance companies needed to be enhanced. The proposed European Union Solvency II Directive makes this very explicit and the current economic turmoil has put a much stronger emphasis on the whole process: it is being seen as the right thing to do, rather than simply a regulatory requirement. In this paper, we set out the background to and recent history of governance for U.K. insurance companies, and consider how enterprise risk management can bring together the various control frameworks needed to support that governance. Whilst no two companies are the same, and hence the solutions to these issues will vary, there are several common themes linked to successful implementation. Similarly, various barriers to success are identified, together with solutions to resolve them.
Teflon amorphous fluoropolymer (TAF) multi-walled carbon nanotube (MWCNT) suspensions have the potential for creating conductive coatings on insulating films for numerous applications. However, there are few studies on polymer MWCNT suspension properties and even fewer that use Teflon. To define mechanical and electrical property relationships, bilayer films of TAF-MWCNT were created with differing concentrations of MWCNTs. Nanoindentation revealed that addition of 8 wt% MWCNTs to TAF increased the elastic modulus by about 25% and hardness by about 15%. Conducting indentation showed 8 wt% MWCNT films exhibit uniform stable conductance once indentation depth exceeds several hundred nanometers. Films with lower concentrations of CNTs were insulating. The two techniques provide a unique description of structure property relationships in this suspension film system.
The draft paper sets out the authors' views of what good practice for the actuarial aspects of internal models will look like in 2012, the year Solvency II is expected to be implemented. Actuaries working on internal models can expect to have to follow such practices if their internal models are to be approved for use in calculating regulatory capital. The paper is therefore relevant for actuaries who plan to work on internal model implementation for Solvency II.
Moreover, the risk quantification techniques discussed in the paper can also be used in the Own Risk Solvency Assessment (ORSA) process also required by Solvency II. The paper is therefore relevant to actuaries working in companies that are not planning to apply to use an internal model.
The paper covers both life and non-life insurance and reinsurance, and reviews current practice as well as setting out possible future practice. This leads to identification of areas for research by the Profession to prepare for 2012 and an indication of the directions this work might take.
The paper is effectively a work in progress, and readers should ask themselves what they should do in response to the ideas discussed.
Outcomes following admission to residential alternatives to standard in-patient mental health services are underresearched.
Aims
To explore short-term outcomes and costs of admission to alternative and standard services.
Method
Health of the Nation Outcome Scales (HoNOS), Threshold Assessment Grid (TAG), Global Assessment of Functioning (GAF) and admission cost data were collected for six alternative services and six standard services.
Results
All outcomes improved during admission for both types of service (n = 433). Adjusted improvement was greater for standard services in scores on HoNOS (difference 1.99, 95% CI 1.12–2.86), TAG (difference 1.40, 95% CI 0.39–2.51) and GAF functioning (difference 4.15, 95% CI 1.08–7.22) but not GAF symptoms. Admissions to alternatives were 20.6 days shorter, and hence cheaper (UK£3832 v. £9850). Standard services cost an additional £2939 per unit HoNOS improvement.
Conclusions
The absence of clear-cut advantage for either type of service highlights the importance of the subjective experience and longer-term costs.