To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Systematic, national surveillance of outbreaks of intestinal infectious disease has been undertaken by Public Health England (PHE) since 1992. Between 1992 and 2002, there were 19 outbreaks linked to raw drinking milk (RDM) or products made using raw milk, involving 229 people; 36 of these were hospitalised. There followed an eleven-year period (2003–2013) where no outbreaks linked to RDM were reported. However, since 2014 seven outbreaks of Escherichia coli O157:H7 (n = 3) or Campylobacter jejuni (n = 4) caused by contaminated RDM were investigated and reported. Between 2014 and 2017, there were 114 cases, five reported hospitalisations and one death. The data presented within this review indicated that the risk of RDM has increased since 2014. Despite the labelling requirements and recommendations that children should not consume RDM, almost a third of outbreak cases were children. In addition, there has been an increase in consumer popularity and in registered RDM producers in the UK. The Food Standards Agency (FSA) continue to provide advice on RDM to consumers and have recently made additional recommendations to enhance existing controls around registration and hygiene of RDM producers.
Non-tuberculous mycobacterium encephalitis is rare. Since 2013, a global outbreak of Mycobacterium chimaera infection has been attributed to point-source contamination of heater cooler units used in cardiac surgery. Disseminated M. chimaera infection has presented many unique challenges, including non-specific clinical presentations with delays in diagnosis, and a high mortality rate among predominantly immunocompetent adults. Here, we describe three patients with fatal disseminated Mycobacterium chimaera infection showing initially non-specific, progressively worsening neurocognitive decline, including confusion, delirium, depression and apathy. Autopsy revealed widespread granulomatous encephalitis of the cerebrum, brain stem and spinal cord, along with granulomatous chorioretinitis. Cerebral involvement and differentiation between mycobacterial granulomas and microangiopathic changes can be assessed best on MRI with contrast enhancement. The prognosis of M. chimaera encephalitis appears to be very poor, but might be improved by increased awareness of this new syndrome and timely antimicrobial treatment.
This presentation will enable the learner to:
1.Describe the clinical, radiological and neuropathological findings of Mycobacterium chimaera encephalitis
2.Be aware of this rare form of encephalitis, and explain its diagnosis, prognosis and management
Older adults presenting with mild cognitive impairment (MCI) have a higher risk of developing dementia and also demonstrate impairments in social cognition. This study sought to establish whether in people with MCI, poorer theory of mind (ToM) was associated with volumetric changes in the amygdala and hippocampus, as well as early changes in behaviour.
One hundred and fourteen people with MCI and fifty-two older adult controls completed the Reading the Mind in the Eyes Test (RMET), while close informants (e.g., spouse/family member/friend/carer) described any current behavioural changes using the Revised Cambridge Behavioural Inventory (CBI-R). A subsample of participants completed structural magnetic resonance imaging (MRI).
The MCI group showed poorer performance on all neuropsychological tests administered, and moderate reductions on the RMET compared to the control group (d = .44), with greater reduction observed in those with amnestic compared to non-amnestic MCI (p = .03). While a robust correlation was identified between poorer RMET performance and smaller hippocampal volume in the control group (ρ = .53, p = .01), this relationship was not apparent in the MCI group (ρ = .21, p = .11). In the MCI group, poorer RMET performance was associated with poorer everyday skills (ρ = −.26, p = .01) assessed by the CBI-R.
Our findings cross-validate previous reports that social cognitive deficits in ToM are a feature of MCI and also suggest that disruptions to broader neural networks are likely to be implicated. Furthermore, ToM deficits in MCI are associated with a decline in everyday skills such as writing or paying bills.
Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.
Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.
Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.
This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.
One major challenge facing policy-makers is to design education and workplace training programs that are appropriately challenging. We review previous research that suggests that difficult training is better than easy training. However, surveys we conducted of students and of expert sport coaches showed that many prescribed easy rather than difficult training for those they coached. We analyzed the performance of National Collegiate Athletic Association (NCAA) basketball teams in postseason tournaments to see whether the existing research, largely on individuals in short-term situations, would generalize to teams in the long run. Indeed, playing difficult nonconference (training) games modestly improved performance for NCAA teams in the postseason. Difficult training particularly benefitted teams that lost many nonconference games, and the effect of difficulty was positive within the range of difficulty NCAA teams actually encounter, making it clear that difficult training is superior. We suggest that our results can be generalized beyond sports, although with careful consideration of differences between NCAA basketball teams and other teams that may limit generalizability. These results suggest that policy-makers might consider amplifying the difficulty of team training exercises under certain conditions.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
Shiga toxin-producing Escherichia coli (STEC) infection can cause serious illness including haemolytic uraemic syndrome. The role of socio-economic status (SES) in differential clinical presentation and exposure to potential risk factors amongst STEC cases has not previously been reported in England. We conducted an observational study using a dataset of all STEC cases identified in England, 2010–2015. Odds ratios for clinical characteristics of cases and foodborne, waterborne and environmental risk factors were estimated using logistic regression, stratified by SES, adjusting for baseline demographic factors. Incidence was higher in the highest SES group compared to the lowest (RR 1.54, 95% CI 1.19–2.00). Odds of Accident and Emergency attendance (OR 1.35, 95% CI 1.10–1.75) and hospitalisation (OR 1.71, 95% CI 1.36–2.15) because of illness were higher in the most disadvantaged compared to the least, suggesting potential lower ascertainment of milder cases or delayed care-seeking behaviour in disadvantaged groups. Advantaged individuals were significantly more likely to report salad/fruit/vegetable/herb consumption (OR 1.59, 95% CI 1.16–2.17), non-UK or UK travel (OR 1.76, 95% CI 1.40–2.27; OR 1.85, 95% CI 1.35–2.56) and environmental exposures (walking in a paddock, OR 1.82, 95% CI 1.22–2.70; soil contact, OR 1.52, 95% CI 2.13–1.09) suggesting other unmeasured risks, such as person-to-person transmission, could be more important in the most disadvantaged group.
The USA is currently enduring an opioid crisis. Identifying cost-effective, easy-to-implement behavioral measures that predict treatment outcomes in opioid misusers is a crucial scientific, therapeutic, and epidemiological goal.
The current study used a mixed cross-sectional and longitudinal design to test whether a behavioral choice task, previously validated in stimulant users, was associated with increased opioid misuse severity at baseline, and whether it predicted change in opioid misuse severity at follow-up. At baseline, data from 100 prescription opioid-treated chronic pain patients were analyzed; at follow-up, data were analyzed in 34 of these participants who were non-misusers at baseline. During the choice task, participants chose under probabilistic contingencies whether to view opioid-related images in comparison with affectively pleasant, unpleasant, and neutral images. Following previous procedures, we also assessed insight into choice behavior, operationalized as whether (yes/no) participants correctly self-reported the image category they chose most often.
At baseline, the higher choice for viewing opioid images in direct comparison with pleasant images was associated with opioid misuse and impaired insight into choice behavior; the combination of these produced especially elevated opioid-related choice behavior. In longitudinal analyses of individuals who were initially non-misusers, higher baseline opioid v. pleasant choice behavior predicted more opioid misuse behaviors at follow-up.
These results indicate that greater relative allocation of behavior toward opioid stimuli and away from stimuli depicting natural reinforcement is associated with concurrent opioid misuse and portends vulnerability toward future misuse. The choice task may provide important medical information to guide opioid-prescribing practices.
Poor compliance of prescription medication is an ongoing public health crisis. Nearly half of patients do not take their medication as prescribed, harming their own health while also increasing public health care costs. Despite these detrimental consequences, prior research has struggled to establish cost-effective and scalable interventions to improve adherence rates. We suggest that one reason for the limited success of prior interventions is that they make the personal health costs of non-adherence insufficiently prominent, while a higher saliency of these costs may motivate patients to adhere more. In the current research, we test whether an intervention that makes the personal health costs of non-compliance more salient for patients will increase their medication adherence. To do so, we conducted a randomized controlled trial with 16,191 patients across 278 UK pharmacies over a 9-month time period and manipulated the perceived consequences of medication non-adherence. We find that patients who received a treatment highlighting the personal health costs of non-compliance were significantly more likely to adhere to their medication than three comparison groups (odds ratio = 1.84, 95% confidence interval = 1.37–2.47). Shifting patients’ focus to the personal health costs of non-compliance may thus offer a potentially cost-effective and scalable approach to improving medication adherence.
We sought to define the prevalence of echocardiographic abnormalities in long-term survivors of paediatric hematopoietic stem cell transplantation and determine the utility of screening in asymptomatic patients. We analysed echocardiograms performed on survivors who underwent hematopoietic stem cell transplantation from 1982 to 2006. A total of 389 patients were alive in 2017, with 114 having an echocardiogram obtained ⩾5 years post-infusion. A total of 95 patients had echocardiogram performed for routine surveillance. The mean time post-hematopoietic stem cell transplantation was 13 years. Of 95 patients, 77 (82.1%) had ejection fraction measured, and 10/77 (13.0%) had ejection fraction z-scores ⩽−2.0, which is abnormally low. Those patients with abnormal ejection fraction were significantly more likely to have been exposed to anthracyclines or total body irradiation. Among individuals who received neither anthracyclines nor total body irradiation, only 1/31 (3.2%) was found to have an abnormal ejection fraction of 51.4%, z-score −2.73. In the cohort of 77 patients, the negative predictive value of having a normal ejection fraction given no exposure to total body irradiation or anthracyclines was 96.7% at 95% confidence interval (83.3–99.8%). Systolic dysfunction is relatively common in long-term survivors of paediatric hematopoietic stem cell transplantation who have received anthracyclines or total body irradiation. Survivors who are asymptomatic and did not receive radiation or anthracyclines likely do not require surveillance echocardiograms, unless otherwise indicated.
This work reports by the first time a method to control the geometry of Ga2O3 films nanocrystallites at 350 °C. The formation of controlled shaped nano-crystallites of γ-Ga2O3 from amorphous Ga2O3 films grown by RF-Sputtering at room temperature driven by nano-layers of group IB metals (Cu, Ag or Au) is studied. The reported results can be explained by the role of subsurface metal nano-layers and the non-equilibrium nature of the sputtering processes. To study the effects on the surface structure and their optical properties arrays of amorphous-Ga2O3/IB-metal/amorphous-Ga2O3 were annealed in dry N2 atmosphere at 350 °C by 50, 100 and 150 min. The experimental results can be explained by the evolution of the amorphous character of the films amorphous films towards the nanocrystalline γ-Ga2O3 phase driven by the metal nano-layer seed nature. As the annealing time was increased the transition from amorphous-Ga2O3 to the nanocrystalline γ-Ga2O3 phase was detected by X-ray diffraction analysis. The transition to the nanocrystalline γ-Ga2O3 is demonstrated by the formation of octahedral, triangle and ball shape nanocrystallites with sizes of ∼5 to 50 nm according to FE-SEM analysis. The influence of the metal nano-layer is clearly seen by the shift of the plasmon frequency resonance produced by the Ga2O3/IB-metal/Ga2O3 arrays in the region from 400 to 600 nm caused by the modification of the interface Ga2O3/IB-metal produced by the applied annealing stages.
A linear stability analysis of a two-layer plane Couette flow of two immiscible fluid layers with different densities, viscosities and thicknesses, bounded by two infinite parallel plates moving at a constant relative velocity to each other, with an insoluble surfactant monolayer along the interface and in the presence of gravity is carried out. The normal modes approach is applied to the equations governing flow disturbances in the two layers. These equations, together with boundary conditions at the plates and the interface, yield a linear eigenvalue problem. When inertia is neglected the velocity amplitudes are the linear combinations of certain hyperbolic functions, and a quadratic dispersion equation for the increment, that is the complex growth rate, is obtained, where coefficients depend on the aspect ratio, the viscosity ratio, the basic velocity shear, the Marangoni number
that measures the effects of surfactant and the Bond number
that measures the influence of gravity. An extensive investigation is carried out that examines the stabilizing or destabilizing influences of these parameters. Since the dispersion equation is quadratic in the growth rate, there are two continuous branches of the normal modes: a robust branch that exists even with no surfactant, and a surfactant branch that, to the contrary, vanishes when
. Regimes have been uncovered with crossings of the two dispersion curves, their reconnections at the point of crossing and separations as
changes. Due to the availability of the explicit forms for the growth rates, in many instances the numerical results are corroborated with analytical asymptotics.
The joint effects of an insoluble surfactant and gravity on the linear stability of a two-layer Couette flow in a horizontal channel are investigated. The inertialess instability regimes are studied for arbitrary wavelengths and with no simplifying requirements on the system parameters: the ratio of thicknesses of the two fluid layers; the viscosity ratio; the base shear rate; the Marangoni number
; and the Bond number
. As was established in the first part of this investigation (Frenkel, Halpern & Schweiger, J. Fluid Mech., vol. 863, 2019, pp. 150–184), a quadratic dispersion equation for the complex growth rate yields two, largely continuous, branches of the normal modes, which are responsible for the flow stability properties. This is consistent with the surfactant instability case of zero gravity studied in Halpern & Frenkel (J. Fluid Mech., vol. 485, 2003, pp. 191–220). The present paper focuses on the mid-wave regimes of instability, defined as those having a finite interval of unstable wavenumbers bounded away from zero. In particular, the location of the mid-wave instability regions in the (
)-plane, bounded by their critical curves, depending on the other system parameters, is considered. The changes of the extremal points of these critical curves with the variation of external parameters are investigated, including the bifurcation points at which new extrema emerge. Also, it is found that for the less unstable branch of normal modes, a mid-wave interval of unstable wavenumbers may sometimes coexist with a long-wave one, defined as an interval having a zero-wavenumber endpoint.
The forward rate of dissolution of the International Simple Glass (ISG) was determined under alkaline conditions at 40 °C using the Single Pass Flow Through (SPFT) method. Forward rates were consistent with those obtained in the literature for this glass composition. The formation of altered gel layers and surface pits was observed on the surface of glass particles, especially at the very highest pH values, despite the application of high flow rates to prevent the build-up of solubility limiting phases. These features could be attributed to preferential localized dissolution at sites with a higher alkali concentration or from a separate, less durable, vitreous phase. These results may indicate that surface pit and altered gel formation occurs under the forward rate of dissolution as imposed by the SPFT method, particularly for simplified borosilicate glass materials.
The effects of growing pinto peanut mixed with elephant grass-based pastures are still little known. The aim of the current research was to evaluate the performance of herbage yield, nutritive value of forage and animal responses to levels of pinto peanut forage mass mixed with elephant grass in low-input systems. Three grazing systems were evaluated: (i) elephant grass-based (control); (ii) pinto peanut, low-density forage yield (63 g/kg of dry matter – DM) + elephant grass; and (iii) pinto peanut, high-density dry matter forage yield (206 g/kg DM) + elephant grass. The experimental design was completely randomized with the three treatments (grazing systems) and three replicates (paddocks) in split-plot grazing cycles. Forage samples were collected to evaluate the pasture and animal responses. Leaf blades of elephant grass and the other companion grasses of pinto peanut were collected to analyse the crude protein, in vitro digestible organic matter and total digestible nutrients. The pinto peanut, high-density dry matter forage yield + elephant grass treatment was found to give the best results in terms of herbage yield, forage intake and stocking rate, as well as having higher crude protein contents for both elephant grass and the other grasses, followed by pinto peanut with low-density forage yield + elephant grass and finally elephant grass alone. Better results were found with the grass–legume system for pasture and animal responses.
Antarctic silverfish (Pleuragramma antarctica Boulenger) are a keystone species in the Ross Sea. Silverfish eggs and larvae are abundant during spring amongst the sub-surface platelet ice in Terra Nova Bay. It is not known whether the eggs are spawned elsewhere and accumulate under the ice or whether there is mass migration of silverfish to coastal spawning sites in winter. To test the latter hypothesis, an upward-looking 67 kHz echo sounder was moored in Terra Nova Bay to observe potential silverfish migration. The echo sounder was deployed at 380 m in a seabed depth of 550 m and ran for 210 days from 15 May until 11 December 2015. Acoustic reflections consistent with silverfish were observed at depths of 230–380 m during 9–22 September. This timing is consistent with the presence of eggs typically observed in October. Adult silverfish were also detected with an echo sounder and camera deployed through the ice in McMurdo Sound on 10 November 2015. Juvenile silverfish, but not adults, were observed through the ice in Terra Nova Bay during 11–16 November 2017. This paper provides a proof of concept, showing that innovative use of acoustics may help fill important observation gaps in the life history of silverfish.
The current study examined the concurrent and prospective associations of ethnic–racial identity content (i.e., centrality, private regard, and public regard) and depressive symptomatology among Latino adolescents. Data were drawn from a longitudinal study of Latino adolescents (N = 148, 53.4% girls) who were 13–14 years old at Wave 1. Results indicated that higher ethnic–racial centrality at Waves 1 and 2 predicted fewer depressive symptoms at Waves 2 and 3, respectively. In addition, more positive private regard at Wave 1 predicted fewer depressive symptoms at Wave 2, and more positive public regard at Wave 2 predicted fewer symptoms at Wave 3. Thus, ethnic–racial identity content may serve as a cultural protective factor that is linked to diminished depressive symptomatology among Latino youth.
We observed pediatric S. aureus hospitalizations decreased 36% from 26.3 to 16.8 infections per 1,000 admissions from 2009 to 2016, with methicillin-resistant S. aureus (MRSA) decreasing by 52% and methicillin-susceptible S. aureus decreasing by 17%, among 39 pediatric hospitals. Similar decreases were observed for days of therapy of anti-MRSA antibiotics.