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Altered DNA methylation in the FK506 binding protein 5 (FKBP5) gene has been shown to regulate stress response, which may serve as a biomarker of depression and a promising candidate for explaining sexual differences. However, there is no consistent conclusion so far.
The present study aimed to test the associations of FKBP5 DNA methylation with depressive symptoms and whether these associations were influenced by sex.
A nested case-control study comprising 87 cases and 151 controls was conducted in South China from January 2019 and December 2019. Peripheral blood for DNA extraction and DNA methylation analysis of FKBP5 gene promoter was collected, and severity of depressive symptoms was assessed at baseline and after one year follow-up.
Compared to healthy controls, lower methylation percentage of FKBP5-12 CpG 1 was observed in adolescents with depressive symptoms after adjusting covariates (case: 0.94 ± 2.00, control: 0.47 ± 0.92; F = 5.41, P = 0.021). In addition, hypomethylation of FKBP5 CpG sites was not an independent risk factor for depressive symptoms after adjustment for environmental stress factors (P > 0.05). No significant sex differences were found in the association of FKBP5 gene methylation with depressive symptoms.
Lower levels of FKBP5 methylation were found in adolescents with depressive symptoms. Our study supported that the epigenetic factors did not act alone in the development of depressive symptoms. Taken together, these findings contribute to a better understanding of complex mechanisms of gene-environment interactions involved in depression.
Adolescents spend more time on the Internet than adults, making them susceptible to problematic Internet use (PIU). Evidence shows that PIU has a negative impact on self-esteem among adolescents, disturbing the development of emotional regulation, which makes them more likely to develop depressive symptoms subsequently. However, there is lack of literature focusing on the process that self-esteem may mediate the association between PIU and depressive symptoms.
This study aimed to examine the prospective links between PIU, self-esteem, and depressive symptoms in adolescence.
A total of 1,736 adolescents completed this longitudinal study. The baseline survey was conducted in 2019, and the follow-up surveys were performed at 1-year and 2-year later. Problematic Internet use, self-esteem, and depressive symptoms were measured. A cascade model was used to examine the longitudinal associations between PIU, self-esteem, and depressive symptoms.
The mean (SD) age of participants was 13.6 (1.5) years at baseline. The final results observed significant within-time associations between PIU, self-esteem, and depressive symptoms at each time point. PIU and low level of self-esteem could predict subsequent depressive symptoms among adolescents, and depressive symptoms were also associated with subsequent PIU and self-esteem.
Both problematic Internet use and self-esteem show bidirectional predictions with depressive symptoms among Chinese adolescents. Health-related professionals, schools and families should be aware of the findings of bidirectional associations. Adolescents with problematic Internet use and lower self-esteem should be paid more attention to attenuate the risk of developing depressive symptoms.
Glutamatergic dysfunction has been implicated in sensory integration deficits in schizophrenia, yet how glutamatergic function contributes to behavioural impairments and neural activities of sensory integration remains unknown.
Fifty schizophrenia patients and 43 healthy controls completed behavioural assessments for sensory integration and underwent magnetic resonance spectroscopy (MRS) for measuring the anterior cingulate cortex (ACC) glutamate levels. The correlation between glutamate levels and behavioural sensory integration deficits was examined in each group. A subsample of 20 pairs of patients and controls further completed an audiovisual sensory integration functional magnetic resonance imaging (fMRI) task. Blood Oxygenation Level Dependent (BOLD) activation and task-dependent functional connectivity (FC) were assessed based on fMRI data. Full factorial analyses were performed to examine the Group-by-Glutamate Level interaction effects on fMRI measurements (group differences in correlation between glutamate levels and fMRI measurements) and the correlation between glutamate levels and fMRI measurements within each group.
We found that schizophrenia patients exhibited impaired sensory integration which was positively correlated with ACC glutamate levels. Multimodal analyses showed significantly Group-by-Glutamate Level interaction effects on BOLD activation as well as task-dependent FC in a ‘cortico-subcortical-cortical’ network (including medial frontal gyrus, precuneus, ACC, middle cingulate gyrus, thalamus and caudate) with positive correlations in patients and negative in controls.
Our findings indicate that ACC glutamate influences neural activities in a large-scale network during sensory integration, but the effects have opposite directionality between schizophrenia patients and healthy people. This implicates the crucial role of glutamatergic system in sensory integration processing in schizophrenia.
Experimental studies of the influence of fluid–structure interaction on cloud cavitation about a stiff stainless steel (SS) and a flexible composite (CF) hydrofoil have been presented in Parts I (Smith et al., J. Fluid Mech., vol. 896, 2020a, p. A1) and II (Smith et al., J. Fluid Mech., vol. 897, 2020b, p. A28). This work further analyses the data and complements the measurements with reduced-order model predictions to explain the complex response. A two degrees-of-freedom steady-state model is used to explain why the tip bending and twisting deformations are much higher for the CF hydrofoil, while the hydrodynamic load coefficients are very similar. A one degree-of-freedom dynamic model, which considers the spanwise bending deflection only, is used to capture the dynamic response of both hydrofoils. Peaks in the frequency response spectrum are observed at the re-entrant jet-driven and shock-wave-driven cavity shedding frequencies, system bending frequency and heterodyne frequencies caused by the mixing of the two cavity shedding frequencies. The predictions capture the increase of the mean system bending frequency and wider bandwidth of frequency modulation with decreasing cavitation number. The results show that, in general, the amplitude of the deformation fluctuation is higher, but the amplitude of the load fluctuation is lower for the CF hydrofoil compared with the SS hydrofoil. Significant dynamic load amplification is observed at subharmonic lock-in when the shock-wave-driven cavity shedding frequency matches with the nearest subharmonic of the system bending frequency of the CF hydrofoil. Both measurements and predictions show an absence of dynamic load amplification at primary lock-in because of the low intensity of cavity load fluctuations with high cavitation number.
Background: Medulloblastoma (MB) is the most common solid malignant pediatric brain neoplasm. Group 3 (G3) MB, particularly MYC amplified G3 MB, is the most aggressive subgroup with the highest frequency of children presenting with metastatic disease, and is associated with a poor prognosis. To further our understanding of the role of MSI1 in MYC amplified G3 MB, we performed an unbiased integrative analysis of eCLIP binding sites, with changes observed at the transcriptome, the translatome, and the proteome after shMSI1 inhibition. Methods: Primary human pediatric MBs, SU_MB002 and HD-MB03 were kind gifts from Dr. Yoon-Jae Cho (Harvard, MS) and Dr. Till Milde (Heidelberg) and cultured for in vitro and in vivo experiments. eCLIP, RNA-seq, Polysome-seq, and TMT-MS were completed as previously described. Results:MSI1 is overexpressed in G3 MB. shRNA Msi1 interference resulted in a reduction in tumour burden conferring a survival advantage to mice injected with shMSI1 G3MB cells. Robust ranked multiomic analysis (RRA) identified an unconventional gene set directly perturbed by MSI1 in G3 MB. Conclusions: Our robust unbiased integrative analysis revealed a distinct role for MSI1 in the maintenance of the stem cell state in G3 MB through post-transcriptional modification of multiple pathways including identification of unconventional targets such as HIPK1.
Major depressive disorder (MDD) is a common, debilitating, phenotypically heterogeneous disorder with heritability ranges from 30% to 50%. Compared to other psychiatric disorders, its high prevalence, moderate heritability, and strong polygenicity have posed major challenges for gene-mapping in MDD. Studies of common genetic variation in MDD, driven by large international collaborations such as the Psychiatric Genomics Consortium, have confirmed the highly polygenic nature of the disorder and implicated over 100 genetic risk loci to date. Rare copy number variants associated with MDD risk were also recently identified. The goal of this review is to present a broad picture of our current understanding of the epidemiology, genetic epidemiology, molecular genetics, and gene–environment interplay in MDD. Insights into the impact of genetic factors on the aetiology of this complex disorder hold great promise for improving clinical care.
Supraglacial lakes and rivers dominate the storage and transport of meltwater on the southwest Greenland Ice Sheet (GrIS) surface. Despite functioning as interconnected hydrologic networks, supraglacial lakes and rivers are commonly studied as independent features, resulting in an incomplete understanding of their collective impact on meltwater storage and routing. We use Landsat 8 satellite imagery to assess the seasonal evolution of supraglacial lakes and rivers on the southwest GrIS during the 2015 melt season. Remotely sensed meltwater areas and volumes are compared with surface runoff simulations from three climate models (MERRA-2, MAR 3.6 and RACMO 2.3), and with in situ observations of proglacial discharge in the Watson River. We find: (1) at elevations >1600 m, 21% of supraglacial lakes and 28% of supraglacial rivers drain into moulins, signifying the presence of high-elevation surface-to-bed meltwater connections even during a colder-than-average melt season; (2) while supraglacial lakes dominate instantaneous surface meltwater storage, supraglacial rivers dominate total surface meltwater area and discharge; (3) the combined surface area of supraglacial lakes and rivers is strongly correlated with modeled surface runoff; and (4) of the three models examined here, MERRA-2 runoff yields the highest overall correlation with observed proglacial discharge in the Watson River.
This research communication addressed the hypothesis that late lactation cows offered an oat-grain-based supplement or a high level of α-TOC supplementation at pasture would have improved milk composition and processability. Over a grazing period of 49 d, 48 Holstein Friesian dairy cows were randomly assigned to one of four dietary treatments. The dietary treatments were: control, pasture only (CTRL), pasture + 2.65 kg DM barley-based concentrate + 350 IU α-TOC/kg (BARLO), pasture + 2.65 kg DM oat-based concentrate + 350 IU α-TOC/kg (OATLO) and pasture + 2.65 kg DM oat-based concentrate + 1050 IU α-TOC/kg (OATHI). Within this randomised complete block design experiment cows were blocked on days in milk (DIM) and balanced for parity, milk yield and composition. Rennet coagulation time (RCT) was reduced in milk from cows offered OATHI compared to CTRL cows and OATLO. Concentration of conjugated linoleic acid (CLA) was increased by OATHI compared to OATLO and in OATLO compared to CTRL. Supplementation with OATHI reduced individual saturated fatty acids (SFAs) in milk compared to OATLO. In conclusion, supplementing grazing dairy cows with an oat-based supplement improved total milk CLA concentration compared to pasture only. Offering a high level of α-TOC (2931 IU/d) to dairy cows reduced RCT, individual SFA and increased total CLA concentration of milk compared to a lower α-TOC level (738 IU α-TOC/d).
Patients with schizophrenia and individuals with schizotypy, a subclinical group at risk for schizophrenia, have been found to have impairments in cognitive control. The Dual Mechanisms of Cognitive Control (DMC) framework hypothesises that cognitive control can be divided into proactive and reactive control. However, it is unclear whether individuals with schizotypy have differential behavioural impairments and neural correlates underlying these two types of cognitive control.
Twenty-five individuals with schizotypy and 26 matched healthy controls (HCs) completed both reactive and proactive control tasks with electroencephalographic data recorded. The proportion of congruent and incongruent trials was manipulated in a classic colour-word Stroop task to induce proactive or reactive control. Proactive control was induced in a context with mostly incongruent (MI) trials and reactive control in a context with mostly congruent (MC) trials. Two event-related potential (ERP) components, medial frontal negativity (MFN, associated with conflict detection) and conflict sustained potential (conflict SP, associated with conflict resolution) were examined.
There was no significant difference between the two groups in terms of behavioural results. In terms of ERP results, in the MC context, HC exhibited significantly larger MFN (360–530 ms) and conflict SP (600–1000 ms) amplitudes than individuals with schizotypy. The two groups did not show any significant difference in MFN or conflict SP in the MI context.
The present findings provide initial evidence for dissociation of neural activation between proactive and reactive cognitive control in individuals with schizotypy. These findings help us understand cognitive control deficits in the schizophrenia spectrum.
The coronavirus disease 2019 (COVID-19) pandemic represents an unprecedented threat to mental health. Herein, we assessed the impact of COVID-19 on subthreshold depressive symptoms and identified potential mitigating factors.
Participants were from Depression Cohort in China (ChiCTR registry number 1900022145). Adults (n = 1722) with subthreshold depressive symptoms were enrolled between March and October 2019 in a 6-month, community-based interventional study that aimed to prevent clinical depression using psychoeducation. A total of 1506 participants completed the study in Shenzhen, China: 726 participants, who completed the study between March 2019 and January 2020 (i.e. before COVID-19), comprised the ‘wave 1’ group; 780 participants, who were enrolled before COVID-19 and completed the 6-month endpoint assessment during COVID-19, comprised ‘wave 2’. Symptoms of depression, anxiety and insomnia were assessed at baseline and endpoint (i.e. 6-month follow-up) using the Patient Health Questionnaire-9 (PHQ-9), Generalised Anxiety Disorder-7 (GAD-7) and Insomnia Severity Index (ISI), respectively. Measures of resilience and regular exercise were assessed at baseline. We compared the mental health outcomes between wave 1 and wave 2 groups. We additionally investigated how mental health outcomes changed across disparate stages of the COVID-19 pandemic in China, i.e. peak (7–13 February), post-peak (14–27 February), remission plateau (28 February−present).
COVID-19 increased the risk for three mental outcomes: (1) depression (odds ratio [OR] = 1.30, 95% confidence interval [CI]: 1.04–1.62); (2) anxiety (OR = 1.47, 95% CI: 1.16–1.88) and (3) insomnia (OR = 1.37, 95% CI: 1.07–1.77). The highest proportion of probable depression and anxiety was observed post-peak, with 52.9% and 41.4%, respectively. Greater baseline resilience scores had a protective effect on the three main outcomes (depression: OR = 0.26, 95% CI: 0.19–0.37; anxiety: OR = 1.22, 95% CI: 0.14–0.33 and insomnia: OR = 0.18, 95% CI: 0.11–0.28). Furthermore, regular physical activity mitigated the risk for depression (OR = 0.79, 95% CI: 0.79–0.99).
The COVID-19 pandemic exerted a highly significant and negative impact on symptoms of depression, anxiety and insomnia. Mental health outcomes fluctuated as a function of the duration of the pandemic and were alleviated to some extent with the observed decline in community-based transmission. Augmenting resiliency and regular exercise provide an opportunity to mitigate the risk for mental health symptoms during this severe public health crisis.
Late-life depression has substantial impacts on individuals, families and society. Knowledge gaps remain in estimating the economic impacts associated with late-life depression by symptom severity, which has implications for resource prioritisation and research design (such as in modelling). This study examined the incremental health and social care expenditure of depressive symptoms by severity.
We analysed data collected from 2707 older adults aged 60 years and over in Hong Kong. The Patient Health Questionnaire-9 (PHQ-9) and the Client Service Receipt Inventory were used, respectively, to measure depressive symptoms and service utilisation as a basis for calculating care expenditure. Two-part models were used to estimate the incremental expenditure associated with symptom severity over 1 year.
The average PHQ-9 score was 6.3 (standard deviation, s.d. = 4.0). The percentages of respondents with mild, moderate and moderately severe symptoms and non-depressed were 51.8%, 13.5%, 3.7% and 31.0%, respectively. Overall, the moderately severe group generated the largest average incremental expenditure (US$5886; 95% CI 1126–10 647 or a 272% increase), followed by the mild group (US$3849; 95% CI 2520–5177 or a 176% increase) and the moderate group (US$1843; 95% CI 854–2831, or 85% increase). Non-psychiatric healthcare was the main cost component in a mild symptom group, after controlling for other chronic conditions and covariates. The average incremental association between PHQ-9 score and overall care expenditure peaked at PHQ-9 score of 4 (US$691; 95% CI 444–939), then gradually fell to negative between scores of 12 (US$ - 35; 95% CI - 530 to 460) and 19 (US$ -171; 95% CI - 417 to 76) and soared to positive and rebounded at the score of 23 (US$601; 95% CI -1652 to 2854).
The association between depressive symptoms and care expenditure is stronger among older adults with mild and moderately severe symptoms. Older adults with the same symptom severity have different care utilisation and expenditure patterns. Non-psychiatric healthcare is the major cost element. These findings inform ways to optimise policy efforts to improve the financial sustainability of health and long-term care systems, including the involvement of primary care physicians and other geriatric healthcare providers in preventing and treating depression among older adults and related budgeting and accounting issues across services.
The present study was undertaken to evaluate the influence of rumen-protected folic acid (RPFA) on slaughter performance, visceral organ and gastrointestinal tract coefficients, and meat quality in lambs. Sixty-six lambs from 120 Hu ewes were selected based on body weight and maternal diets and then assigned to six groups using a randomised block experimental design in a 3 × 2 factorial arrangement. The first factor was folic acid (FA) as RPFA in the maternal diet (0 mg/kg (M0F), 16 mg/kg (M16F) or 32 mg/kg (M32F) on DM basis). The second factor was FA in the lambs’ diet from weaning until slaughter (0 mg/kg (OC) or 4·0 mg/kg (OF)). The results indicated that the addition of 16 mg/kg FA to the maternal diet increased pre-slaughter weight (PSW), dressing and meat percentage, the reticulum and omasum coefficients, length of the jejunum and ileum, tail fat and perirenal fat coefficient and a* value of the meat colour. The addition of RPFA to the lambs’ diet increased PSW, dressing and meat percentage, eye muscle area, abomasum weight, weight and length of the small intestine, but reduced the coefficients of tail fat. An M × O interaction was observed for the weights of heart, lungs, rumen and total stomach, weight and coefficient of omental fat and the girth rib value. Collectively, RPFA in the maternal and lambs’ diet improved slaughter performance and meat quality by stimulating the morphological development of the gastrointestinal tract and the distribution of fat in the body.
Imaging of cellular layers in a gut-on-a-chip system has been confined to two-dimensional (2D)-imaging through conventional light microscopy and confocal laser scanning microscopy (CLSM) yielding three-dimensional- and 2D-cross-sectional reconstructions. However, CLSM requires staining and is unsuitable for longitudinal visualization. Here, we compare merits of optical coherence tomography (OCT) with those of CLSM and light microscopy for visualization of intestinal epithelial layers during protection by a probiotic Bifidobacterium breve strain and a simultaneous pathogen challenge by an Escherichia coli strain. OCT cross-sectional images yielded film thicknesses that coincided with end-point thicknesses derived from cross-sectional CLSM images. Light microscopy on histological sections of epithelial layers at the end-point yielded smaller layer thicknesses than OCT and CLSM. Protective effects of B. breve adhering to an epithelial layer against an E. coli challenge included the preservation of layer thickness and membrane surface coverage by epithelial cells. OCT does not require staining or sectioning, making OCT suitable for longitudinal visualization of biological films, but as a drawback, OCT does not allow an epithelial layer to be distinguished from bacterial biofilms adhering to it. Thus, OCT is ideal to longitudinally evaluate epithelial layers under probiotic protection and pathogen challenges, but proper image interpretation requires the application of a second method at the end-point to distinguish bacterial and epithelial films.
To examine participants’ experiences with nutrition education classes that were implemented with and designed to complement a cost-offset community-supported agriculture (CSA) programme.
Qualitative analysis of data from twenty-eight focus groups with ninety-six participants enrolled in Farm Fresh Foods for Healthy Kids (F3HK). Transcribed data were coded and analysed by a priori and emergent themes.
Rural and micropolitan communities in New York, North Carolina, Vermont and Washington (USA).
Ninety-six F3HK participants.
Participants found recipes and class activities helpful and reported improvements in nutrition knowledge, food preservation skills and home cooking behaviours for themselves and their children; they also reported that classes promoted a sense of community. Some educators better incorporated CSA produce into lessons, which participants reported as beneficial. Other obligations and class logistics were barriers to attendance; participants recommended that lessons be offered multiple times weekly at different times of day. Other suggestions included lengthening class duration to encourage social engagement; emphasising recipes to incorporate that week’s CSA produce and pantry staples and offering additional strategies to incorporate children in classes.
Complementing a cost-offset CSA with nutrition education may enhance programme benefits to low-income families by improving nutrition knowledge and cooking behaviours. However, future interventions will benefit from ongoing coordination between educators and local growing trajectories to maximise timely coverage of unfamiliar produce in lessons; synchronous scheduling of CSA pick-up and classes for participant convenience and creative strategies to engage children and/or provide childcare.
Klebsiella pneumoniae is a common pathogen associated with nosocomial infections and is characterised serologically by capsular polysaccharide (K) and lipopolysaccharide O antigens. We surveyed a total of 348 non-duplicate K. pneumoniae clinical isolates collected over a 1-year period in a tertiary care hospital, and determined their O and K serotypes by sequencing of the wbb Y and wzi gene loci, respectively. Isolates were also screened for antimicrobial resistance and hypervirulent phenotypes; 94 (27.0%) were identified as carbapenem-resistant (CRKP) and 110 (31.6%) as hypervirulent (hvKP). isolates fell into 58 K, and six O types, with 92.0% and 94.2% typeability, respectively. The predominant K types were K14K64 (16.38%), K1 (14.66%), K2 (8.05%) and K57 (5.46%), while O1 (46%), O2a (27.9%) and O3 (11.8%) were the most common. CRKP and hvKP strains had different serotype distributions with O2a:K14K64 (41.0%) being the most frequent among CRKP, and O1:K1 (26.4%) and O1:K2 (17.3%) among hvKP strains. Serotyping by gene sequencing proved to be a useful tool to inform the clinical epidemiology of K. pneumoniae infections and provides valuable data relevant to vaccine design.
Schizotypy refers to schizophrenia-like traits below the clinical threshold in the general population. The pathological development of schizophrenia has been postulated to evolve from the initial coexistence of ‘brain disconnection’ and ‘brain connectivity compensation’ to ‘brain connectivity decompensation’.
In this study, we examined the brain connectivity changes associated with schizotypy by combining brain white matter structural connectivity, static and dynamic functional connectivity analysis of diffusion tensor imaging data and resting-state functional magnetic resonance imaging data. A total of 87 participants with a high level of schizotypal traits and 122 control participants completed the experiment. Group differences in whole-brain white matter structural connectivity probability, static mean functional connectivity strength, dynamic functional connectivity variability and stability among 264 brain sub-regions of interests were investigated.
We found that individuals with high schizotypy exhibited increased structural connectivity probability within the task control network and within the default mode network; increased variability and decreased stability of functional connectivity within the default mode network and between the auditory network and the subcortical network; and decreased static mean functional connectivity strength mainly associated with the sensorimotor network, the default mode network and the task control network.
These findings highlight the specific changes in brain connectivity associated with schizotypy and indicate that both decompensatory and compensatory changes in structural connectivity within the default mode network and the task control network in the context of whole-brain functional disconnection may be an important neurobiological correlate in individuals with high schizotypy.
The dendrite morphologies of the cast nickel-based superalloy CMSX-4® (CMSX-4® is registered trademarks of the Cannon-Muskegon Corporation) and the austenitic stainless steel HP microalloy have been obtained via an automated serial-sectioning process which allows three-dimensional (3D) microstructural characterization. The dendrite arm spacing, volume fraction of segregation, and fraction of porosity have been determined. This technique not only increases the depth, scope, and level of detailed microstructural characterization but also delivers microstructural data for modeling and simulation.
In this paper, the generation of relativistic electron mirrors (REM) and the reflection of an ultra-short laser off the mirrors are discussed, applying two-dimension particle-in-cell simulations. REMs with ultra-high acceleration and expanding velocity can be produced from a solid nanofoil illuminated normally by an ultra-intense femtosecond laser pulse with a sharp rising edge. Chirped attosecond pulse can be produced through the reflection of a counter-propagating probe laser off the accelerating REM. In the electron moving frame, the plasma frequency of the REM keeps decreasing due to its rapid expansion. The laser frequency, on the contrary, keeps increasing due to the acceleration of REM and the relativistic Doppler shift from the lab frame to the electron moving frame. Within an ultra-short time interval, the two frequencies will be equal in the electron moving frame, which leads to the resonance between laser and REM. The reflected radiation near this interval and corresponding spectra will be amplified due to the resonance. Through adjusting the arriving time of the probe laser, a certain part of the reflected field could be selectively amplified or depressed, leading to the selective adjustment of the corresponding spectra.
Introduction: Physician metrics extracted from an electronic medical records (EMR) system can be utilized for practice improvement. One key metric analyzed at many emergency departments (EDs) is ‘patients per hour’ (pts/hr), a proxy for physician productivity. It is often believed that early-career physicians experience rapid growth in efficiency as they acclimatize to a hospital system and develop clinical confidence. This is the first study to evaluate the following question: Do early-career ED physicians increase their productivity when beginning practice? Methods: We performed a retrospective review of EMR data of early-career ED physicians working at one or more urban, academic centers. Early-career physicians must have started practice within three months of residency completion, and were identified by privileging records and provincial medical college registration. Physicians were excluded if they did not have at least 36 months of continuous data. Monthly productivity data (pts/hr) was extracted for each physician for their first 36-months of practice. A ‘performance curve’ or graph with a trendline of productivity as a moving average was created for each physician. Each performance curve was visually evaluated by two independent reviewers to qualitatively identify the general trend as upward, downward, or stable, with disagreements resolved by conference. Each physician's first and third year average productivity was compared quantitatively as well, with a significant upward or downward trend defined as a difference of at least 0.2 pts/hr. Results: A total of 41 physicians met the inclusion and exclusion criteria. Overall monthly pts/hr averages ranged from 1.08 to 7.65. Upon visual inspection, six (14.6%) physicians had upward trends, five (12.2%) had downward trends, and 30 (73.2%) had no discernable pattern. The quantitative analysis comparing first year to third year productivity matched the qualitative inspection exactly, with the same six physicians showing increased productivity, five with decreased, and 30 without significant change. Notably, the majority (30/41) of physicians demonstrated radical productivity variations over short periods with no discernable long-term trends. Conclusion: The majority of early career physicians do not demonstrate sustained early-career productivity changes. Of those that do, an approximately equal number will become faster and slower.
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.