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Although researchers have described numerous risk factors for salmonellosis and for infection with specific common serotypes, the drivers of Salmonella serotype diversity among human populations remain poorly understood. In this retrospective observational study, we partition records of serotyped non-typhoidal Salmonella isolates from human clinical specimens reported to CDC national surveillance by demographic, geographic and seasonal characteristics and adapt sample-based rarefaction methods from the field of community ecology to study how Salmonella serotype diversity varied within and among these populations in the USA during 1996–2016. We observed substantially higher serotype richness in children <2 years old than in older children and adults and steadily increasing richness with age among older adults. Whereas seasonal and regional variation in serotype diversity was highest among infants and young children, variation by specimen source was highest in adults. Our findings suggest that the risk for infection from uncommon serotypes is associated with host and environmental factors, particularly among infants, young children and older adults. These populations may have a higher proportion of illness acquired through environmental transmission pathways than published source attribution models estimate.
To enhance enrollment into randomized clinical trials (RCTs), we proposed electronic health record-based clinical decision support for patient–clinician shared decision-making about care and RCT enrollment, based on “mathematical equipoise.”
As an example, we created the Knee Osteoarthritis Mathematical Equipoise Tool (KOMET) to determine the presence of patient-specific equipoise between treatments for the choice between total knee replacement (TKR) and nonsurgical treatment of advanced knee osteoarthritis.
With input from patients and clinicians about important pain and physical function treatment outcomes, we created a database from non-RCT sources of knee osteoarthritis outcomes. We then developed multivariable linear regression models that predict 1-year individual-patient knee pain and physical function outcomes for TKR and for nonsurgical treatment. These predictions allowed detecting mathematical equipoise between these two options for patients eligible for TKR. Decision support software was developed to graphically illustrate, for a given patient, the degree of overlap of pain and functional outcomes between the treatments and was pilot tested for usability, responsiveness, and as support for shared decision-making.
The KOMET predictive regression model for knee pain had four patient-specific variables, and an r2 value of 0.32, and the model for physical functioning included six patient-specific variables, and an r2 of 0.34. These models were incorporated into prototype KOMET decision support software and pilot tested in clinics, and were generally well received.
Use of predictive models and mathematical equipoise may help discern patient-specific equipoise to support shared decision-making for selecting between alternative treatments and considering enrollment into an RCT.
We present observations of 50 deg2 of the Mopra carbon monoxide (CO) survey of the Southern Galactic Plane, covering Galactic longitudes l = 300–350° and latitudes |b| ⩽ 0.5°. These data have been taken at 0.6 arcmin spatial resolution and 0.1 km s−1spectral resolution, providing an unprecedented view of the molecular clouds and gas of the Southern Galactic Plane in the 109–115 GHz J = 1–0 transitions of 12CO, 13CO, C18O, and C17O.
We present a series of velocity-integrated maps, spectra, and position-velocity plots that illustrate Galactic arm structures and trace masses on the order of ~106 M⊙ deg−2, and include a preliminary catalogue of C18O clumps located between l = 330–340°. Together with the information about the noise statistics of the survey, these data can be retrieved from the Mopra CO website and the PASA data store.
The main goal of this paper is to provide insights into swash flow dynamics, generated by a non-breaking solitary wave on a steep slope. Both laboratory experiments and numerical simulations are conducted to investigate the details of runup and rundown processes. Special attention is given to the evolution of the bottom boundary layer over the slope in terms of flow separation, vortex formation and the development of a hydraulic jump during the rundown phase. Laboratory experiments were performed to measure the flow velocity fields by means of high-speed particle image velocimetry (HSPIV). Detailed pathline patterns of the swash flows and free-surface profiles were also visualized. Highly resolved computational fluid dynamics (CFD) simulations were carried out. Numerical results are compared with laboratory measurements with a focus on the velocities inside the boundary layer. The overall agreement is excellent during the initial stage of the runup process. However, discrepancies in the model/data comparison grow as time advances because the numerical model does not simulate the shoreline dynamics accurately. Introducing small temporal and spatial shifts in the comparison yields adequate agreement during the entire rundown process. Highly resolved numerical solutions are used to study physical variables that are not measured in laboratory experiments (e.g. pressure field and bottom shear stress). It is shown that the main mechanism for vortex shedding is correlated with the large pressure gradient along the slope as the rundown flow transitions from supercritical to subcritical, under the developing hydraulic jump. Furthermore, the bottom shear stress analysis indicates that the largest values occur at the shoreline and that the relatively large bottom shear stress also takes place within the supercritical flow region, being associated with the backwash vortex system rather than the plunging wave. It is clearly demonstrated that the combination of laboratory observations and numerical simulations have indeed provided significant insights into the swash flow processes.
To determine whether probiotic prophylaxes reduce the odds of Clostridium difficile infection (CDI) in adults and children.
Individual participant data (IPD) meta-analysis of randomized controlled trials (RCTs), adjusting for risk factors.
We searched 6 databases and 11 grey literature sources from inception to April 2016. We identified 32 RCTs (n=8,713); among them, 18 RCTs provided IPD (n=6,851 participants) comparing probiotic prophylaxis to placebo or no treatment (standard care). One reviewer prepared the IPD, and 2 reviewers extracted data, rated study quality, and graded evidence quality.
Probiotics reduced CDI odds in the unadjusted model (n=6,645; odds ratio [OR] 0.37; 95% confidence interval [CI], 0.25–0.55) and the adjusted model (n=5,074; OR, 0.35; 95% CI, 0.23–0.55). Using 2 or more antibiotics increased the odds of CDI (OR, 2.20; 95% CI, 1.11–4.37), whereas age, sex, hospitalization status, and high-risk antibiotic exposure did not. Adjusted subgroup analyses suggested that, compared to no probiotics, multispecies probiotics were more beneficial than single-species probiotics, as was using probiotics in clinical settings where the CDI risk is ≥5%. Of 18 studies, 14 reported adverse events. In 11 of these 14 studies, the adverse events were retained in the adjusted model. Odds for serious adverse events were similar for both groups in the unadjusted analyses (n=4,990; OR, 1.06; 95% CI, 0.89–1.26) and adjusted analyses (n=4,718; OR, 1.06; 95% CI, 0.89–1.28). Missing outcome data for CDI ranged from 0% to 25.8%. Our analyses were robust to a sensitivity analysis for missingness.
Moderate quality (ie, certainty) evidence suggests that probiotic prophylaxis may be a useful and safe CDI prevention strategy, particularly among participants taking 2 or more antibiotics and in hospital settings where the risk of CDI is ≥5%.
Antineuronal antibodies are associated with psychosis, although their clinical significance in first episode of psychosis (FEP) is undetermined.
To examine all patients admitted for treatment of FEP for antineuronal antibodies and describe clinical presentations and treatment outcomes in those who were antibody positive.
Individuals admitted for FEP to six mental health units in Queensland, Australia, were prospectively tested for serum antineuronal antibodies. Antibody-positive patients were referred for neurological and immunological assessment and therapy.
Of 113 consenting participants, six had antineuronal antibodies (anti-N-methyl-D-aspartate receptor antibodies [n = 4], voltage-gated potassium channel antibodies [n = 1] and antibodies against uncharacterised antigen [n = 1]). Five received immunotherapy, which prompted resolution of psychosis in four.
A small subgroup of patients admitted to hospital with FEP have antineuronal antibodies detectable in serum and are responsive to immunotherapy. Early diagnosis and treatment is critical to optimise recovery.
Ultrasound (US) detects synovitis more accurately than clinical examination (CE) in people with rheumatoid arthritis (RA). This review aimed to investigate the use of US, compared to CE alone, in treatment strategies for RA, and to estimate its potential to be cost-effective in making treatment decisions.
A systematic review was conducted of studies: investigating RA treatment response or strategies that compared US with CE-assessed synovitis; and of tapering RA treatment (1). A model was constructed to investigate the potential cost-effectiveness of US in (i) selecting patients suitable for treatment tapering; and (ii) avoiding treatment escalation (2).
Seven prospective cohort studies suggested US-detected synovitis was significantly associated with a treatment response or tapering failure, whereas in most cases clinical examination alone was not. Two randomized controlled trials (RCTs) identified suggested that US added to the Disease Activity Index (DAS)-based treatment strategies but did not significantly improve primary outcomes, but was associated with improved rate of DAS remission. The evidence showed that some patients (proportions varied widely) who had achieved low disease activity could have treatment tapered, with no, or little, short-term harm to the patient.
The model estimated that an average reduction of 2.5 percent in the costs of biological disease-modifying anti-rheumatic drug (bDMARDs) was sufficient to cover the costs of performing US every three months. This value increased to 4 percent and 13 percent for the costs of conventional disease-modifying anti-rheumatic drug (cDMARDs) depending on the assumed regimen.
Use of US to monitor synovitis could potentially be a cost-effective approach, given that low proportions of patients for whom clinicians consider amending treatment, would need to taper treatment, or remain on therapy without escalation. US could provide clinicians with more confidence in reducing the drug burden. However, there is considerable uncertainty in this conclusion due to lack of robust data relating to key parameters.
Introduction: Point-of-care ultrasound (POCUS) has been suggested as an initial investigation in the management of renal colic. Our objectives were: 1) to determine the accuracy of POCUS for the diagnosis of nephrolithiasis, and 2) to assess its prognostic value in the management of renal colic (PROSPERO: 42016035331). Methods: An electronic database search of MEDLINE, EMBASE, and PubMed was conducted utilizing subject headings, keywords, and synonyms that address our research question. Bibliographies of included studies and narrative reviews were manually examined. Studies of adult emergency department patients with renal colic symptoms were included. Any degree of hydronephrosis was considered a positive POCUS finding. Accepted criterion standards were CT evidence of renal stone or hydronephrosis, direct stone visualization, or surgical findings. Screening of abstracts, quality assessment with the QUADAS-2 instrument, and data extraction were performed by two reviewers, with discrepancies resolved by conference with a third reviewer.Test performance was assessed by pooled sensitivity and specificity, calculated likelihood ratios, and a summary receiver operator curve (SROC). The secondary outcome of prognostic value was reported as a narrative summary. Results: The electronic search yielded 627 unique titles. After relevance screening, 25 papers underwent full-text review, and 8 articles met all inclusion criteria. Of these, 5 high-quality studies (N=1773) were included in the meta-analysis for diagnostic accuracy, and three yielded data on prognostic value. The pooled results for sensitivity and specificity were 70.2% (95% CI=67.1% to 73.2%) and 75.4% (95% CI=72.5% to 78.2%), respectively. The calculated positive and negative likelihood ratios were 2.85 and 0.39. The SROC generated did not show evidence of a threshold effect.Three studies examining prognostic value noted a higher likelihood of a large stone or surgical intervention with positive POCUS findings. The largest randomized trial showed lower cumulative radiation exposure and no increase in adverse events in those who received POCUS investigation as the initial renal colic investigation. Conclusion: Point-of-care ultrasound is of modest accuracy for the diagnosis of nephrolithiasis. While positive POCUS findings are associated with larger stones and greater likelihood for intervention, the clinical importance of this is unclear.
To measure transmission frequencies and risk factors for household acquisition of community-associated and healthcare-associated (HA-) methicillin-resistant Staphylococcus aureus (MRSA).
Prospective cohort study from October 4, 2008, through December 3, 2012.
Seven acute care hospitals in or near Toronto, Canada.
Total of 99 MRSA-colonized or MRSA-infected case patients and 183 household contacts.
Baseline interviews were conducted, and surveillance cultures were collected monthly for 3 months from household members, pets, and 8 prespecified high-use environmental locations. Isolates underwent pulsed-field gel electrophoresis and staphylococcal cassette chromosome mec typing.
Overall, of 183 household contacts 89 (49%) were MRSA colonized, with 56 (31%) detected at baseline. MRSA transmission from index case to contacts negative at baseline occurred in 27 (40%) of 68 followed-up households. Strains were identical within households. The transmission risk for HA-MRSA was 39% compared with 40% (P=.95) for community-associated MRSA. HA-MRSA index cases were more likely to be older and not practice infection control measures (P=.002–.03). Household acquisition risk factors included requiring assistance and sharing bath towels (P=.001–.03). Environmental contamination was identified in 78 (79%) of 99 households and was more common in HA-MRSA households.
Household transmission of community-associated and HA-MRSA strains was common and the difference in transmission risk was not statistically significant.
Flexible electronics has emerged as a very promising field, in particular,wearable, bendable, and stretchable strain sensors with high sensitivity which could be used for human motion detection, sports performance monitoring, etc. In this paper, a highly stretchable and sensitive strain sensor composed of reduced graphene oxide foam and elastomer composite is fabricated by assembly and followed by a polymer immersing process. The strain sensor has demonstrated high stretchability and sensitivity. Furthermore, the device was employed for gauging muscle-induced strain which results in high sensitivity and reproducibility. The developed strain sensors showed great application potential in fields of biomechanical systems.
Carbapenem-resistant Acinetobacter baumannii (CRAB) with diverse multilocus sequence typing emerged among our nursing home residents (6.5%) with a high background rate of MRSA (32.2%). Rectal swabs yielded a higher rate of CRAB detection than axillary or nasal swabs. Bed-bound status, use of adult diapers, and nasogastric tube were risk factors for CRAB colonization.
The current Ebola virus disease (EVD) epidemic in West Africa is unprecedented in scale, and Sierra Leone is the most severely affected country. The case fatality risk (CFR) and hospitalization fatality risk (HFR) were used to characterize the severity of infections in confirmed and probable EVD cases in Sierra Leone. Proportional hazards regression models were used to investigate factors associated with the risk of death in EVD cases. In total, there were 17 318 EVD cases reported in Sierra Leone from 23 May 2014 to 31 January 2015. Of the probable and confirmed EVD cases with a reported final outcome, a total of 2536 deaths and 886 recoveries were reported. CFR and HFR estimates were 74·2% [95% credibility interval (CrI) 72·6–75·5] and 68·9% (95% CrI 66·2–71·6), respectively. Risks of death were higher in the youngest (0–4 years) and oldest (⩾60 years) age groups, and in the calendar month of October 2014. Sex and occupational status did not significantly affect the mortality of EVD. The CFR and HFR estimates of EVD were very high in Sierra Leone.
Therapeutic nihilism on treating psychopathy is widespread and is largely based on many outdated and poorly designed studies. Important recent advances have been made in assessing psychopathy and recidivism risks, as well as in offender rehabilitation to reduce reoffending, all of which are now well supported by a considerable literature based on credible empirical research. A 2-component model to guide risk reduction treatment of psychopathy has been proposed based on the integration of key points from the 3 bodies of literature. Treatment programs in line with the model have been in operation, and the results of early outcome evaluations are encouraging. Important advances also have been made in understanding the possible etiology of mentally disordered offenders with schizophrenia and history of criminality and violence, some with significant features of psychopathy. This article presents a review of recent research on risk reduction treatment of psychopathy with the additional aim to extend the research to the treatment of mentally disordered offenders with schizophrenia, violence, and psychopathy.
We present observations of the first 10° of longitude in the Mopra CO survey of the southern Galactic plane, covering Galactic longitude l = 320–330° and latitude b = ±0.5°, and l = 327–330°, b = +0.5–1.0°. These data have been taken at 35-arcsec spatial resolution and 0.1 km s−1 spectral resolution, providing an unprecedented view of the molecular clouds and gas of the southern Galactic plane in the 109–115 GHz J = 1–0 transitions of 12CO, 13CO, C18O, and C17O. Together with information about the noise statistics from the Mopra telescope, these data can be retrieved from the Mopra CO website and the CSIRO-ATNF data archive.
The Museum of the Great Temple of Tenochtitlan in Mexico City holds a collection of several thousands of polished stone artifacts that were excavated and identified as temple offerings. These can stratigraphically be related to the sequential construction stages (II-VII) of the ceremonial area of the Aztec capital from the foundation of the city in 1325 to 1521, when the Spaniards conquered the city. A non-destructive investigation of the elemental and chemical composition of these archaeological artifacts helps us to understand the provenance of these pieces, their use and the specific mineralogical choice for these artifacts as well as more information regarding trade routes relevant to the development of the Aztec empire. A mineralogical analysis of, in total, 450 stone artifacts was carried out using infrared spectroscopy (FTIR) and X-ray Fluorescence (XRF). From this, eighty-five pieces were selected according to their excavation location, either in the Great Temple itself or in the surrounding buildings, as well as to represent the different construction stages of the area (this is part of a World Heritage Site). The resulting mineralogical and chemical information was related to possible mineral resources that were controlled and used as the empire expanded. Artifacts made from high-status semi-precious minerals, like jadeite and turquoise, are found to be concentrated in the central buildings and in the Great Temple itself, but also in the later construction periods of the area.
Colonial mural painting developed in Mexico in XVI century after the conquest of the pre-Hispanic cultures following the evangelization process little information exists about the chronology of the paintings and workshops, the painters, the pictorial techniques or the materiality of this art work.
In this work, we present the non-invasive methodology of study of the pigments and other components of nine mural paintings in three colonial Augustinian ex-convents located in Epazoyucan, Actopan and Ixmiquilpan, in the state of Hidalgo, central Mexico. These places were selected not only because of the inherent value and iconographic characteristics of the paintings, which date to the XVI and XVII century, but also because they are in the same region and are well preserved and in good condition. Then it is possible to compare their materiality and get new information to answer to some of questions related to these paintings.
X-ray Fluorescence (XRF) and Raman spectroscopy were conducted using portable equipment on scaffolds after a global examination under ultraviolet light. We were able to distinguish between different pigments used for different colors such as vermillion, orpiment, and a copper pigment, for the bright red, gold yellow, and green, respectively. These pigments are characteristic of the known Mexican Colonial color palette. Apart from this, we also found the presence of indigo in the blues, minium, and cochineal. A first comparison among the mural paintings of the three sites indicates different palettes and painting periods.
To assess the effectiveness of infection control preparedness for human infection with influenza A H7N9 in Hong Kong.
A descriptive study of responses to the emergence of influenza A H7N9.
A university-affiliated teaching hospital.
Healthcare workers (HCWs) with unprotected exposure (not wearing N95 respirator during aerosol-generating procedure) to a patient with influenza A H7N9.
A bundle approach including active and enhanced surveillance, early airborne infection isolation, rapid molecular diagnostic testing, and extensive contact tracing for HCWs with unprotected exposure was implemented. Seventy HCWs with unprotected exposure to an index case were interviewed especially regarding their patient care activities.
From April 1, 2013, through May 31, 2014, a total of 126 (0.08%) of 163,456 admitted patients were tested for the H7 gene by reverse transcription-polymerase chain reaction per protocol. Two confirmed cases were identified. Seventy (53.8%) of 130 HCWs had unprotected exposure to an index case, whereas 41 (58.6%) and 58 (82.9%) of 70 HCWs wore surgical masks and practiced hand hygiene after patient care, respectively. Sixteen (22.9%) of 70 HCWs were involved in high-risk patient contacts. More HCWs with high-risk patient contacts received oseltamivir prophylaxis (P=0.088) and significantly more had paired sera collected for H7 antibody testing (P<0.001). Ten (14.3%) of 70 HCWs developed influenza-like illness during medical surveillance, but none had positive results by reverse transcription-polymerase chain reaction. Paired sera was available from 33 of 70 HCWs with unprotected exposure, and none showed seroconversion against H7N9.
Despite the delay in airborne precautions implementation, no patient-to-HCW transmission of influenza A H7N9 was demonstrated.
Medicine is a science of uncertainty and an art of probability.
Sir William Osler
Decision trees and Markov cohort models, as described and illustrated in the previous chapters, are essentially macrosimulation models. Such models simulate cohorts or groups of subjects. A number of limitations exist to the use of these models. Markov cohort models, for example, have ‘no memory’, implying that subjects in a particular state are a homogeneous group. Techniques to overcome these limitations, such as expanding the number of states, using tunnel states, or using alternative modeling techniques, were discussed in Chapter 10. These techniques can get very complex when dealing with extensive heterogeneity within a population. Microsimulation using Monte Carlo analysis provides another powerful technique to account for heterogeneity across subjects. Microsimulation with Monte Carlo analysis was introduced in Chapter 10 as an alternative method for evaluating a Markov model. In this chapter it will be discussed at greater length in the context of simulating heterogeneity.
In the previous chapters we represented uncertainty with probabilities. Implicitly the assumption was that, even though we were unsure of whether an event would take place, we could nevertheless predict or estimate the probability (or relative frequency) that it would occur. In essence we were using deterministic models. In reality, however, we are also uncertain of the degree of uncertainty. In other words, rather than dealing with a fixed probability we are actually dealing with a distribution of possible values of probabilities. Not only are we uncertain about the probabilities we use in our models, but we are also uncertain about the effectiveness outcomes and cost estimates included in the analysis. Thus, every parameter value we enter into our models is better represented as a probabilistic variable rather than a deterministic variable. If there is a single uncertain parameter, e.g., the relative risk reduction of an intervention, then the 95% confidence interval (CI) of this parameter is commonly used to indicate the uncertainty of the effect. Uncertainty in two or more components requires more complex methods, such as Monte Carlo probabilistic sensitivity analysis, which we will also discuss in this chapter.
Values are what we care about. As such, values should be the driving force for our decision making. They should be the basis for the time and effort we spend thinking about decisions. But this is not the way it is. It is not even close to the way it is.
Value judgments underlie virtually all clinical decisions. Sometimes the decision rests on a comparison of probability alone, such as the probability of surviving an acute episode of illness. In such cases, there is a single outcome measure – the probability of immediate survival – that can be averaged out to arrive at an optimal decision. In most cases, however, decisions between alternative strategies require not only estimates of the probabilities of the associated outcomes, but also value judgments about how to weigh the benefits versus the harms, and how to incorporate other factors like individual preferences for convenience, timing, who makes decisions, who else is affected by the decision, and the like. Consider the following examples.