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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.
This rejoinder begins with an expression of gratitude and broad agreement with the two commentaries by Kenneth Levy and Nicholas Salsman. The rejoinder considers three main issues: (1) the fact of the range of psychodynamic treatments that have been found to be effective in the treatment of personality disorder (PD); (2) the value of considering a dimensional approach to psychopathology in general and PD more specifically, particularly in the context of recent work on the general psychopathology factor; and (3), the issue of transference and different ways of approaching it across different psychodynamic treatments.
This chapter gives an account of the different psychoanalytic traditions and their approaches to PD: the Kleinian/Bionian model, the British object relations perspective, Kohut’s self psychology, the structural object relations model, the interpersonal-relational approach, and mentalizing theory. The chapter goes on to describe two contemporary psychodynamic treatments, along with their evidence base: transference-focused therapy and mentalization-based treatment. Recent developments in the authors’ thinking in relation to PD are then described, partly in the context of recent work in the area of a general psychopathology or “p” factor. In particular, the authors discuss personality disorder in relation to epistemic trust, and suggest that psychopathology might be understood as a form of disordered social cognition, perpetuated by the obstacles to communication that these social cognitive difficulties create. It is postulated that effective therapeutic interventions for PD possess the shared characteristic of stimulating epistemic trust and creating a virtuous circle of improved social communication.
Preferential dissolution of the biogenic carbonate polymorph aragonite promotes preservational bias in shelly marine faunas. While field studies have documented the impact of preferential aragonite dissolution on fossil molluscan diversity, its impact on regional and global biodiversity metrics is debated. Epicontinental seas are especially prone to conditions that both promote and inhibit preferential dissolution, which may result in spatially extensive zones with variable preservation. Here we present a multifaceted evaluation of aragonite dissolution within the Late Cretaceous Western Interior Seaway of North America. Occurrence data of mollusks from two time intervals (Cenomanian/Turonian boundary, early Campanian) are plotted on new high-resolution paleogeographies to assess aragonite preservation within the seaway. Fossil occurrences, diversity estimates, and sampling probabilities for calcitic and aragonitic fauna were compared in zones defined by depth and distance from the seaway margins. Apparent range sizes, which could be influenced by differential preservation potential of aragonite between separate localities, were also compared. Our results are consistent with exacerbated aragonite dissolution within specific depth zones for both time slices, with aragonitic bivalves additionally showing a statistically significant decrease in range size compared with calcitic fauna within carbonate-dominated Cenomanian–Turonian strata. However, we are unable to conclusively show that aragonite dissolution impacted diversity estimates. Therefore, while aragonite dissolution is likely to have affected the preservation of fauna in specific localities, time averaging and instantaneous preservation events preserve regional biodiversity. Our results suggest that the spatial expression of taphonomic biases should be an important consideration for paleontologists working on paleobiogeographic problems.
Improving Access to Psychological Therapies (IAPT) services treat most patients in England who present to primary care with major depression. Psychodynamic psychotherapy is one of the psychotherapies offered. Dynamic Interpersonal Therapy (DIT) is a psychodynamic and mentalization-based treatment for depression. 16 sessions are delivered over approximately 5 months. Neither DIT's effectiveness relative to low-intensity treatment (LIT), nor the feasibility of randomizing patients to psychodynamic or cognitive-behavioural treatments (CBT) in an IAPT setting has been demonstrated.
147 patients were randomized in a 3:2:1 ratio to DIT (n = 73), LIT (control intervention; n = 54) or CBT (n = 20) in four IAPT treatment services in a combined superiority and feasibility design. Patients meeting criteria for major depressive disorder were assessed at baseline, mid-treatment (3 months) and post-treatment (6 months) using the Hamilton Rating Scale for Depression (HRSD-17), Beck Depression Inventory-II (BDI-II) and other self-rated questionnaire measures. Patients receiving DIT were also followed up 6 months post-completion.
The DIT arm showed significantly lower HRSD-17 scores at the 6-month primary end-point compared with LIT (d = 0.70). Significantly more DIT patients (51%) showed clinically significant change on the HRSD-17 compared with LIT (9%). The DIT and CBT arms showed equivalence on most outcomes. Results were similar with the BDI-II. DIT showed benefit across a range of secondary outcomes.
DIT delivered in a primary care setting is superior to LIT and can be appropriately compared with CBT in future RCTs.
Functionally graded materials (FGMs) in which the elemental composition intentionally varies with position can be fabricated using directed energy deposition additive manufacturing (AM). This work examines an FGM that is linearly graded from V to Invar 36 (64 wt% Fe, 36 wt% Ni). This FGM cracked during fabrication, indicating the formation of detrimental phases. The microstructure, composition, phases, and microhardness of the gradient zone were analyzed experimentally. The phase composition as a function of chemistry was predicted through thermodynamic calculations. It was determined that a significant amount of the intermetallic σ-FeV phase formed within the gradient zone. When the σ phase constituted the majority phase, catastrophic cracking occurred. The approach presented illustrates the suitability of using equilibrium thermodynamic calculations for the prediction of phase formation in FGMs made by AM despite the nonequilibrium conditions in AM, providing a route for the computationally informed design of FGMs.
Background: Self-report instruments are commonly used to assess for childhood depressive symptoms. Historically, clinicians have relied heavily on parent-reports due to concerns about childrens’ cognitive abilities to understand diagnostic questions. However, parents may also be unreliable reporters due to a lack of understanding of their child's symptomatology, overshadowing by their own problems, and tendencies to promote themselves more favourably in order to achieve desired assessment goals. One such variable that can lead to unreliable reporting is impression management, which is a goal-directed response in which an individual (e.g. mother or father) attempts to represent themselves, or their child, in a socially desirable way to the observer. Aims: This study examined the relationship between mothers who engage in impression management, as measured by the Parenting Stress Index-Short Form defensive responding subscale, and parent-/child-self-reports of depressive symptomatology in 106 mother–child dyads. Methods: 106 clinic-referred children (mean child age = 10.06 years, range 7–16 years) were administered the Child Depression Inventory, and mothers (mean mother age = 40.80 years, range 27–57 years) were administered the Child-Behavior Checklist, Parenting Stress Index-Short Form, and Symptom Checklist-90-Revised. Results: As predicted, mothers who engaged in impression management under-reported their child's symptomatology on the anxious/depressed and withdrawn subscales of the Child Behavior Checklist. Moreover, the relationship between maternal-reported child depressive symptoms and child-reported depressive symptoms was moderated by impression management. Conclusions: These results suggest that children may be more reliable reporters of their own depressive symptomatology when mothers are highly defensive or stressed.
Political scientists frequently use instrumental variables (IV) estimation to estimate the causal effect of an endogenous treatment variable. However, when the treatment effect is heterogeneous, this estimation strategy only recovers the local average treatment effect (LATE). The LATE is an average treatment effect (ATE) for a subset of the population: units that receive treatment if and only if they are induced by an exogenous IV. However, researchers may instead be interested in the ATE for the entire population of interest. In this article, we develop a simple reweighting method for estimating the ATE, shedding light on the identification challenge posed in moving from the LATE to the ATE. We apply our method to two published experiments in political science in which we demonstrate that the LATE has the potential to substantively differ from the ATE.
To investigate relationships between mortality and circulating 25-hydroxyvitamin D (25(OH)D), 25-hydroxycholecalciferol (25(OH)D3) and 25-hydroxyergocalciferol (25(OH)D2).
Case–cohort study within the Melbourne Collaborative Cohort Study (MCCS). We measured 25(OH)D2 and 25(OH)D3 in archived dried blood spots by LC–MS/MS. Cox regression was used to estimate mortality hazard ratios (HR), with adjustment for confounders.
The MCCS included 29 206 participants, who at recruitment in 1990–1994 were aged 40–69 years, had dried blood spots collected and no history of cancer. For the present study we selected participants who died by 31 December 2007 (n 2410) and a random sample (sub-cohort, n 2996).
The HR per 25 nmol/l increment in concentration of 25(OH)D and 25(OH)D3 were 0·86 (95 % CI 0·78, 0·96; P=0·007) and 0·85 (95 % CI 0·77, 0·95; P=0·003), respectively. Of 5108 participants, sixty-three (1·2 %) had detectable 25(OH)D2; their mean 25(OH)D concentration was 11·9 (95 % CI 7·3, 16·6) nmol/l higher (P<0·001). The HR for detectable 25(OH)D2 was 1·80 (95 % CI 1·09, 2·97; P=0·023); for those with detectable 25(OH)D2, the HR per 25 nmol/l increment in 25(OH)D was 1·06 (95 % CI 0·87, 1·29; P interaction=0·02). HR were similar for participants who reported being in good, very good or excellent health four years after recruitment.
Total 25(OH)D and 25(OH)D3 concentrations were inversely associated with mortality. The finding that the inverse association for 25(OH)D was restricted to those with no detectable 25(OH)D2 requires confirmation in populations with higher exposure to ergocalciferol.
Antimicrobial stewardship programs (ASPs) are variably implemented.
To characterize variations of antimicrobial stewardship structure and practices across all inpatient Veterans Affairs facilities in 2012 and correlate key characteristics with antimicrobial usage.
A web-based survey regarding stewardship activities was administered to each facility’s designated contact. Bivariate associations between facility characteristics and inpatient antimicrobial use during 2012 were determined.
Total of 130 Veterans Affairs facilities with inpatient services.
Of 130 responding facilities, 29 (22%) had a formal policy establishing an ASP, and 12 (9%) had an approved ASP business plan. Antimicrobial stewardship teams were present in 49 facilities (38%); 34 teams included a clinical pharmacist with formal infectious diseases (ID) training. Stewardship activities varied across facilities, including development of yearly antibiograms (122 [94%]), formulary restrictions (120 [92%]), stop orders for antimicrobial duration (98 [75%]), and written clinical pathways for specific conditions (96 [74%]). Decreased antimicrobial usage was associated with having at least 1 full-time ID physician (P=.03), an ID fellowship program (P=.003), and a clinical pharmacist with formal ID training (P=.006) as well as frequency of systematic patient-level reviews of antimicrobial use (P=.01) and having a policy to address antimicrobial use in the context of Clostridium difficile infection (P=.01). Stop orders for antimicrobial duration were associated with increased use (P=.03).
ASP-related activities varied considerably. Decreased antibiotic use appeared related to ID presence and certain select practices. Further statistical assessments may help optimize antimicrobial practices.
Several studies have suggested that dairy food may reduce the risk of obesity and metabolic abnormalities but few have been able to conclusively demonstrate that it reduces the risk of diabetes. The aim of the present analysis was to investigate if dairy food intake independently reduces the risk of diabetes.
The Australian Diabetes Obesity and Lifestyle Study (AusDiab) is a national, population-based, prospective survey conducted over 5 years. Baseline measurements included a 121-item FFQ, anthropometrics and an oral glucose tolerance test.
Forty-two randomly selected clusters across Australia.
Adults aged ≥25 years who participated in the baseline survey and returned to follow-up 5 years later.
A total of 5582 participants with complete data were eligible for analysis, 209 of whom had incident diabetes. Compared with men in the first tertile of dairy food intake, men in the third tertile had a significantly reduced risk of developing diabetes after adjustment for age, sex, total energy intake, family history of diabetes, education, physical activity, smoking status, fasting serum TAG and HDL cholesterol, systolic blood pressure, waist circumference and hip circumference (OR = 0·53, 95 % CI 0·29, 0·96; P = 0·033). A similar non-significant association was observed in women.
Dietary patterns that incorporate high intakes of dairy food may reduce the risk of diabetes among men. Further investigation into the relationship between dairy food intake and diabetes needs to be undertaken to fully understand the potential mechanism of this observation.
The future effects of nitrogen in the environment will depend on the extent of nitrogen use and the practical application techniques of nitrogen in a similar way as in the past. Projections and scenarios are appropriate tools for extrapolating current knowledge into the future. However, these tools will not allow future system turnovers to be predicted.
In principle, scenarios of nitrogen use follow the approaches currently used for air pollution, climate, or ecosystem projections. Short-term projections (to 2030) are developed using a ‘baseline’ path of development, which considers abatement options that are consistent with European policy. For medium-term projections (to 2050) and long-term projections, the European Nitrogen Assessment (ENA) applies a ‘storyline’ approach similar to that used in the IPCC SRES scenarios. Beyond 2050 in particular, such storylines also take into account technological and behavioral shifts.
Key findings/state of knowledge
The ENA distinguishes between driver-oriented and effect-oriented factors determining nitrogen use. Parameters that cause changes in nitrogen fixation or application are called drivers. In a driver-based approach, it is assumed that any variation of these parameters will also trigger a change in nitrogen pollution. In an effect-based approach, as the adverse effects of nitrogen become evident in the environment, introduction of nitrogen abatement legislation requiring the application of more efficient abatement measures is expected. This approach needs to rely on a target that is likely to be maintained in the future (e.g. human health). Nitrogen abatement legislation based on such targets will aim to counter any growth in adverse environmental effects that occur as a result of increased nitrogen application.
Heard Island, a heavily glacierized volcanic island in the Southern Ocean, is 80% ice-covered, with glaciers descending from 2,400 m to sea level: major glaciers are up to 7 km long with areas exceeding 10 km. Much of the island was photographed from the air in 1947 and again in early 1980. Photographs and limited ground surveys record changes (mostly retreats) in glacier fronts. Retreat is most marked on the eastern flanks where former tidewater glaciers are now grounded inland. Glaciers on northern and windward western flanks still end in ice cliffs but have narrowed; glaciers and ice caps on Laurens Peninsula (maximum elevation 710 m) are up to 65% smaller. Nearby lies Kerguelen and other southern islands with long climatic records have warrned significantly since the early 1960s. Surface and upper-air climatic data from Heard Island 1947–54 and records from automatic weather stations 1980–82 suggest that Heard too has warmed slightly, concurrently with a possible northward shift of low-pressure system tracks in this region. Temperatures have remained above average through the early 1980s and glacier retreat is expected to continue.