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Lewy body dementia, consisting of both dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), is considerably under-recognised clinically compared with its frequency in autopsy series.
This study investigated the clinical diagnostic pathways of patients with Lewy body dementia to assess if difficulties in diagnosis may be contributing to these differences.
We reviewed the medical notes of 74 people with DLB and 72 with non-DLB dementia matched for age, gender and cognitive performance, together with 38 people with PDD and 35 with Parkinson's disease, matched for age and gender, from two geographically distinct UK regions.
The cases of individuals with DLB took longer to reach a final diagnosis (1.2 v. 0.6 years, P = 0.017), underwent more scans (1.7 v. 1.2, P = 0.002) and had more alternative prior diagnoses (0.8 v. 0.4, P = 0.002), than the cases of those with non-DLB dementia. Individuals diagnosed in one region of the UK had significantly more core features (2.1 v. 1.5, P = 0.007) than those in the other region, and were less likely to have dopamine transporter imaging (P < 0.001). For patients with PDD, more than 1.4 years prior to receiving a dementia diagnosis: 46% (12 of 26) had documented impaired activities of daily living because of cognitive impairment, 57% (16 of 28) had cognitive impairment in multiple domains, with 38% (6 of 16) having both, and 39% (9 of 23) already receiving anti-dementia drugs.
Our results show the pathway to diagnosis of DLB is longer and more complex than for non-DLB dementia. There were also marked differences between regions in the thresholds clinicians adopt for diagnosing DLB and also in the use of dopamine transporter imaging. For PDD, a diagnosis of dementia was delayed well beyond symptom onset and even treatment.
Results of in situ U–Pb dating of calcite spherulites, cone-in-cone (CIC) calcite and calcite fibres from a calcareous concretion of the upper Ediacaran of Finnmark, Arctic Norway, are reported. Calcite spherulites from the innermost layers of the concretion yielded a lower intercept age of 563 ± 70 Ma, which, although imprecise, is within uncertainty of the age of sedimentation based on fossil assemblages. Non-deformed CIC calcite from the bottom part of the concretion yielded an age of 475 ± 25 Ma, which is interpreted as the age of CIC calcite formation during a period of fluid overpressure induced during burial of the sediments. Deformed CIC calcite from the top part of the concretion yielded an age of 418 ± 23 Ma, which overlaps with a known Caledonian tectono-metamorphic event, and indicates a potential post-depositional overprint at this time. Calcite fibres that grew in small fissures along spherulite rims, which are interpreted as a recrystallization feature during deformation and formation of a cleavage, gave an imprecise age of 486 ± 161 Ma. Our results show that U–Pb dating of calcite can provide age constraints for ancient carbonates and syn- to post-depositional processes that operated during burial and metamorphic overprinting.
At present, analysis of diet and bladder cancer (BC) is mostly based on the intake of individual foods. The examination of food combinations provides a scope to deal with the complexity and unpredictability of the diet and aims to overcome the limitations of the study of nutrients and foods in isolation. This article aims to demonstrate the usability of supervised data mining methods to extract the food groups related to BC. In order to derive key food groups associated with BC risk, we applied the data mining technique C5.0 with 10-fold cross-validation in the BLadder cancer Epidemiology and Nutritional Determinants study, including data from eighteen case–control and one nested case–cohort study, compromising 8320 BC cases out of 31 551 participants. Dietary data, on the eleven main food groups of the Eurocode 2 Core classification codebook, and relevant non-diet data (i.e. sex, age and smoking status) were available. Primarily, five key food groups were extracted; in order of importance, beverages (non-milk); grains and grain products; vegetables and vegetable products; fats, oils and their products; meats and meat products were associated with BC risk. Since these food groups are corresponded with previously proposed BC-related dietary factors, data mining seems to be a promising technique in the field of nutritional epidemiology and deserves further examination.
In response to the increasingly popular manipulation argument against compatibilism, some have argued that libertarian accounts of free will are vulnerable to parallel manipulation arguments, and thus manipulation is not uniquely problematic for compatibilists. The main aim of this article is to give this point a more detailed development than it has previously received. Prior attempts to make this point have targeted particular libertarian accounts but cannot be generalized. By contrast, I provide an appropriately modified manipulation that targets all libertarian accounts of freedom and responsibility—an especially tricky task given that libertarian accounts are a motley set. I conclude that if manipulation arguments reveal any theoretical cost then it is one borne by all accounts according to which we are free and responsible, not by compatibilism in particular.
A physical oceanographic, geophysical and marine geological survey of Edward VIII Gulf, Kemp Coast, collected data from conductivity–temperature–depth casts, multi-beam bathymetric swath mapping and 3.5 kHz sub-bottom surveying. Modified circumpolar deep water (mCDW) is observed in Edward VIII Gulf, as well as notable bathymetric features including mega-scale glacial lineations and a 1750 m-deep trough. Sedimentological, geochemical, rock-magnetic and micropalaeontological analysis of two kasten cores document regional palaeoclimate and palaeo-oceanographic conditions over the past 8000 years, with a warm period occurring from c. 8 to 4 ka and a shift to cooler conditions beginning at c. 4 ka and persisting until at least 0.9 ka. Sediment packages > 40 m thick within deep troughs in Edward VIII Gulf present potential targets for higher-resolution Holocene and deglacial climate studies. Despite the presence of mCDW on the shelf, inland bed topography consisting of highland terrain suggests the likelihood of relative stability of this sector of the East Antarctic Ice Sheet.
True Colours is an automated symptom monitoring programme used by National Health Service psychiatric services. This study explored whether patients with unipolar treatment-resistant depression (TRD) found this a useful addition to their treatment regimes. Semi-structured qualitative interviews were conducted with 21 patients with TRD, who had engaged in True Colours monitoring as part of the Lithium versus Quetiapine in Depression study. A thematic analysis was used to assess participant experiences of the system.
Six main themes emerged from the data, the most notable indicating that mood monitoring increased patients' insight into their disorder, but that subsequent behaviour change was absent.
Patients with TRD can benefit from mood monitoring via True Colours, making it a worthwhile addition to treatment. Further development of such systems and additional support may be required for patients with TRD to experience further benefits as reported by other patient groups.
Gut microbiota data obtained by DNA sequencing are not only complex because of the number of taxa that may be detected within human cohorts, but also compositional because characteristics of the microbiota are described in relative terms (e.g., “relative abundance” of particular bacterial taxa expressed as a proportion of the total abundance of taxa). Nutrition researchers often use standard principal component analysis (PCA) to derive dietary patterns from complex food data, enabling each participant's diet to be described in terms of the extent to which it fits their cohort's dietary patterns. However, compositional PCA methods are not commonly used to describe patterns of microbiota in the way that dietary patterns are used to describe diets. This approach would be useful for identifying microbiota patterns that are associated with diet and body composition. The aim of this study is to use compositional PCA to describe gut microbiota profiles in 5 year old children and explore associations between microbiota profiles, diet, body mass index (BMI) z-score, and fat mass index (FMI) z-score. This study uses a cross-sectional data for 319 children who provided a faecal sample at 5 year of age. Their primary caregiver completed a 123-item quantitative food frequency questionnaire validated for foods of relevance to the gut microbiota. Body composition was determined using dual-energy x-ray absorptiometry, and BMI and FMI z-scores calculated. Compositional PCA identified and described gut microbiota profiles at the genus level, and profiles were examined in relation to diet and body size. Three gut microbiota profiles were found. Profile 1 (positive loadings on Blautia and Bifidobacterium; negative loadings on Bacteroides) was not related to diet or body size. Profile 2 (positive loadings on Bacteroides; negative loadings on uncultured Christensenellaceae and Ruminococcaceae) was associated with a lower BMI z-score (r = -0.16, P = 0.003). Profile 3 (positive loadings on Faecalibacterium, Eubacterium and Roseburia) was associated with higher intakes of fibre (r = 0.15, P = 0.007); total (r = 0.15, P = 0.009), and insoluble (r = 0.13, P = 0.021) non-starch polysaccharides; protein (r = 0.12, P = 0.036); meat (r = 0.15, P = 0.010); and nuts, seeds and legumes (r = 0.11, P = 0.047). Further regression analyses found that profile 2 and profile 3 were independently associated with BMI z-score and diet respectively. We encourage fellow researchers to use compositional PCA as a method for identifying further links between the gut, diet and obesity, and for developing the next generation of research in which the impact on body composition of dietary interventions that modify the gut microbiota is determined.
Dietary Zn has significant impacts on the growth and development of breeding rams. The objectives of this study were to evaluate the effects of dietary Zn source and concentration on serum Zn concentration, growth performance, wool traits and reproductive performance in rams. Forty-four Targhee rams (14 months; 68 ± 18 kg BW) were used in an 84-day completely randomized design and were fed one of three pelleted dietary treatments: (1) a control without fortified Zn (CON; n = 15; ~1 × NRC); (2) a diet fortified with a Zn amino acid complex (ZnAA; n = 14; ~2 × NRC) and (3) a diet fortified with ZnSO4 (ZnSO4; n = 15; ~2 × NRC). Growth and wool characteristics measured throughout the course of the study were BW, average daily gain (ADG), dry matter intake (DMI), feed efficiency (G : F), longissimus dorsi muscle depth (LMD), back fat (BF), wool staple length (SL) and average fibre diameter (AFD). Blood was collected from each ram at four time periods to quantify serum Zn and testosterone concentrations. Semen was collected 1 to 2 days after the trial was completed. There were no differences in BW (P = 0.45), DMI (P = 0.18), LMD (P = 0.48), BF (P = 0.47) and AFD (P = 0.9) among treatment groups. ZnSO4 had greater (P ≤ 0.03) serum Zn concentrations compared with ZnAA and CON treatments. Rams consuming ZnAA had greater (P ≤ 0.03) ADG than ZnSO4 and CON. There tended to be differences among groups for G : F (P = 0.06), with ZnAA being numerically greater than ZnSO4 and CON. Wool staple length regrowth was greater (P < 0.001) in ZnSO4 and tended to be longer (P = 0.06) in ZnAA treatment group compared with CON. No differences were observed among treatments in scrotal circumference, testosterone, spermatozoa concentration within ram semen, % motility, % live sperm and % sperm abnormalities (P ≥ 0.23). Results indicated beneficial effects of feeding increased Zn concentrations to developing Targhee rams, although Zn source elicited differential responses in performance characteristics measured.
To describe an outbreak of bacteremia caused by vancomycin-sensitive Enterococcus faecalis (VSEfe).
An investigation by retrospective case control and molecular typing by whole-genome sequencing (WGS).
A tertiary-care neonatal unit in Melbourne, Australia.
Risk factors for 30 consecutive neonates with VSEfe bacteremia from June 2011 to December 2014 were analyzed using a case control study. Controls were neonates matched for gestational age, birth weight, and year of birth. Isolates were typed using WGS, and multilocus sequence typing (MLST) was determined.
Bacteremia for case patients occurred at a median time after delivery of 23.5 days (interquartile range, 14.9–35.8). Previous described risk factors for nosocomial bacteremia did not contribute to excess risk for VSEfe. WGS typing results designated 43% ST179 as well as 14 other sequence types, indicating a polyclonal outbreak. A multimodal intervention that included education, insertion checklists, guidelines on maintenance and access of central lines, adjustments to the late onset sepsis antibiotic treatment, and the introduction of diaper bags for disposal of soiled diapers after being handled inside the bed, led to termination of the outbreak.
Typing using WGS identified this outbreak as predominately nonclonal and therefore not due to cross transmission. A multimodal approach was then sought to reduce the incidence of VSEfe bacteremia.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
The Louisville Twin Study (LTS) is nationally recognized as one of the largest and most comprehensive studies of child development related to multiple birth status. The LTS is unique because of the extensive longitudinal face-to-face assessments, the frequency of data collection, the inclusion of data on additional family members (i.e., parents, siblings, grandparents; and later, twins’ own spouses and children), and the variety of data collection methods used. Data preservation efforts began in 2008 and are largely complete, although efforts are ongoing to obtain funding to convert the electronic data to a newer format. A pilot study was completed in the summer of 2018 to bring the twins, who are now middle-aged, back for testing. A grant is currently under review to extend the pilot study to include all former participants who are now ≥40 years of age. Opportunities for collaboration are welcome.
Lifelong health is thought to be partially set during intrauterine life by persistent epigenetic changes induced by the prenatal environment. To evaluate this hypothesis, we initiated a prospective longitudinal study in monochorionic (MC) twins: the TwinLIFE study. MC twins are monozygotic, thus in origin genetically identical, and share a single placenta. Although MC twins have many environmental factors in common, in one-third of the MC twin pairs, one fetus has significantly less access to nutrients and resources during pregnancy than its co-twin often resulting in a significant discordance in prenatal growth. Hence, MC twins constitute a unique natural experiment to study the influence of the prenatal environment on health. In TwinLIFE, we will chart intrapair differences in DNA methylation focusing on mesenchymal stromal cells isolated from cord as an advanced proxy of epigenetic dysregulation relevant for long-term health consequences. Next, we will follow up the MC twins for growth, cardiovascular and neurodevelopmental outcomes during childhood and evaluate the impact of an epigenetic signature at birth on future health. The current target is to include 100 MC twin pairs, but we aim to continue enrollment after procuring additional funding. TwinLIFE will not only address an unmet clinical need in the high-risk group of MC twins, but may also advance early-life strategies to prevent adverse growth, cardiovascular and neurodevelopmental outcomes in the general population.
We have observed the G23 field of the Galaxy AndMass Assembly (GAMA) survey using the Australian Square Kilometre Array Pathfinder (ASKAP) in its commissioning phase to validate the performance of the telescope and to characterise the detected galaxy populations. This observation covers ~48 deg2 with synthesised beam of 32.7 arcsec by 17.8 arcsec at 936MHz, and ~39 deg2 with synthesised beam of 15.8 arcsec by 12.0 arcsec at 1320MHz. At both frequencies, the root-mean-square (r.m.s.) noise is ~0.1 mJy/beam. We combine these radio observations with the GAMA galaxy data, which includes spectroscopy of galaxies that are i-band selected with a magnitude limit of 19.2. Wide-field Infrared Survey Explorer (WISE) infrared (IR) photometry is used to determine which galaxies host an active galactic nucleus (AGN). In properties including source counts, mass distributions, and IR versus radio luminosity relation, the ASKAP-detected radio sources behave as expected. Radio galaxies have higher stellar mass and luminosity in IR, optical, and UV than other galaxies. We apply optical and IR AGN diagnostics and find that they disagree for ~30% of the galaxies in our sample. We suggest possible causes for the disagreement. Some cases can be explained by optical extinction of the AGN, but for more than half of the cases we do not find a clear explanation. Radio sources aremore likely (~6%) to have an AGN than radio quiet galaxies (~1%), but the majority of AGN are not detected in radio at this sensitivity.
To determine the impact of pre-operative intratympanic gentamicin injection on the recovery of patients undergoing translabyrinthine resection of vestibular schwannomas.
This prospective, case–control pilot study included eight patients undergoing surgical labyrinthectomy, divided into two groups: four patients who received pre-operative intratympanic gentamicin and four patients who did not. The post-operative six-canal video head impulse test responses and length of in-patient stay were assessed.
The average length of stay was shorter for patients who received intratympanic gentamicin (6.75 days; range, 6–7 days) than for those who did not (9.5 days; range, 8–11 days) (p = 0.0073). Additionally, the gentamicin group had normal post-operative video head impulse test responses in the contralateral ear, while the non-gentamicin group did not.
Pre-operative intratympanic gentamicin improves the recovery following vestibular schwannoma resection, eliminating, as per the video head impulse test, the impact of labyrinthectomy on the contralateral labyrinth.
To examine when cochlear fibrosis occurs following a translabyrinthine approach for vestibular schwannoma resection, and to determine the safest time window for potential cochlear implantation in cases with a preserved cochlear nerve.
This study retrospectively reviewed the post-operative magnetic resonance imaging scans of patients undergoing a translabyrinthine approach for vestibular schwannoma resection, assessing the fluid signal within the cochlea. Cochleae were graded based on the Isaacson et al. system (from grade 0 – no obstruction, to grade 4 – complete obliteration).
Thirty-nine patients fulfilled the inclusion criteria. The cochleae showed no evidence of obliteration in: 75 per cent of patients at six months, 38.5 per cent at one year and 27 per cent beyond one year. Most changes happened between 6 and 12 months after vestibular schwannoma resection, with cases of an unobstructed cochlear decreasing dramatically, from 75 per cent to 38.5 per cent, within this time.
The progress of cochlear obliteration that occurred between 6 and 12 months following vestibular schwannoma resection indicates that the first 6 months provides a safer time window for cochlear patency.
Wave run-up phenomena driven by nonlinear wave interactions with a fixed rectangular box are investigated. Experiments are carried out in different types of uni-directional waves with normal incidence. Significant wave run-ups featuring tertiary interaction effects, similar to those reported by Molin et al. (J. Fluid Mech., vol. 528, 2005, pp. 323–354) for a fixed vertical plate, are observed in regular wave tests. Transient wave group tests are conducted for comparison, to facilitate the analysis of the tertiary interactions in irregular waves. The most striking observation is that the wave surface elevations at the centre of the front face of the fixed box can reach
the incident waves even in irregular waves, much larger than the
predicted from linear theory and observed for the transient groups. The extra amplification builds up slowly and is localized on the weather side of the box. It is believed to result from tertiary interactions between the incident and reflected wave fields upstream, which induce a local lensing effect and thus wave focusing on the weather side. These interactions, though a nonlinear process, occur at the first harmonic quantities rather than high harmonics. Supporting evidence is extracted from random wave runs using NewWave analysis, where surface amplifications and phase lag – both key characteristics of tertiary wave interactions – are identified. The identification of these tertiary interactions in irregular waves is new, and may be of practical importance.
Major depressive disorder (MDD) commonly co-occurs with clinically significant levels of anxiety. However, anxiety symptoms are varied and have been inconsistently associated with clinical, functional, and antidepressant treatment outcomes. We aimed to identify and characterise dimensions of anxiety in people with MDD and their use in predicting antidepressant treatment outcome.
1008 adults with a current diagnosis of single-episode or recurrent, nonpsychotic, MDD were assessed at baseline on clinical features and cognitive/physiological functioning. Participants were then randomised to one of three commonly prescribed antidepressants and reassessed at 8 weeks regarding symptom change, as well as remission and response, on the 17-item Hamilton Rating Scale Depression (HRSD17) and the 16-item Quick Inventory of Depressive Symptomatology (QIDS-SR16). Exploratory factor analysis was used on items from scales assessing anxiety symptoms, and resulting factors were assessed against clinical features and cognitive/physiological functioning. Factors were also assessed on their ability to predict treatment outcome.
Three factors emerged relating to stress, cognitive anxiety, and somatic anxiety. All factors showed high internal consistency, minimal cross-loadings, and unique clinical and functional profiles. Furthermore, only higher somatic anxiety was associated with poorer QIDS-SR16 remission, even after adjusting for covariates and multiple comparisons.
Anxiety symptoms in people with MDD can be separated onto distinct factors that differentially respond to treatment outcome. Furthermore, these factors do not align with subscales of established measures of anxiety. Future research should consider cognitive and somatic symptoms of anxiety separately when assessing anxiety in MDD and their use in predicting treatment outcome.
The 1983 case Racine v Woods is the leading child protection case from the Supreme Court of Canada, distinguishing bonding and/or attachment as a more important determinant of best interest for an Indigenous child than cultural connection. Using this case, courts are upholding the permanent placement of Indigenous children in non-Indigenous homes as opposed to placement within their culture. Racine v Woods reflected knowledge of attachment and family at that time but runs counter to current knowledge. Reconsideration of the factors to decide cross-cultural adoption is needed. The essential point is that attachment assessment draws from a dyadic relational theory and is being applied to communal family systems, such as Indigenous systems. Such a review is consistent with the calls to action of the Truth and Reconciliation Commission (TRC) as well as its predecessor, the Royal Commission on Aboriginal Peoples (RCAP), and recent Canadian Human Rights Tribunal (CHRT) decisions.