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Borderline personality disorder (BPD) is characterized by a heterogeneous clinical phenotype that emerges from interactions among genetic, biological, neurodevelopmental, and psychosocial factors. In the present family study, we evaluated the familial aggregation of key clinical, personality, and neurodevelopmental phenotypes in probands with BPD (n = 103), first-degree biological relatives (n = 74; 43% without a history of psychiatric disorder), and non-psychiatric controls (n = 99).
Participants were assessed on DSM-IV psychiatric diagnoses, symptom dimensions of emotion dysregulation and impulsivity, ‘big five’ personality traits, and neurodevelopmental characteristics, as part of a larger family study on neurocognitive, biological, and genetic markers in BPD.
The most common psychiatric diagnoses in probands and relatives were major depression, substance use disorders, post-traumatic stress disorder, anxiety disorders, and avoidant personality disorder. There was evidence of familial aggregation for specific dimensions of impulsivity and emotion dysregulation, and the big five traits neuroticism and conscientiousness. Both probands and relatives reported an elevated neurodevelopmental history of attentional and behavioral difficulties.
These results support the validity of negative affectivity- and impulse-spectrum phenotypes associated with BPD and its familial risk. Further research is needed to investigate the aggregation of neurocognitive, neural and genetic factors in families with BPD and their associations with core phenotypes underlying the disorder.
BACKGROUND: Meningiomas are the most common primary benign brain tumors in adults. Given the extended life expectancy of most meningiomas, consideration of quality of life (QOL) is important when selecting the optimal management strategy. There is currently a dearth of meningioma-specific QOL tools in the literature. OBJECTIVE: In this systematic review, we analyze the prevailing themes and propose toward building a meningioma-specific QOL assessment tool. METHODS: A systematic search was conducted, and only original studies based on adult patients were considered. QOL tools used in the various studies were analyzed for identification of prevailing themes in the qualitative analysis. The quality of the studies was also assessed. RESULTS: Sixteen articles met all inclusion criteria. Fifteen different QOL assessment tools assessed social and physical functioning, psychological, and emotional well-being. Patient perceptions and support networks had a major impact on QOL scores. Surgery negatively affected social functioning in younger patients, while radiation therapy had a variable impact. Any intervention appeared to have a greater negative impact on physical functioning compared to observation. CONCLUSION: Younger patients with meningiomas appear to be more vulnerable within social and physical functioning domains. All of these findings must be interpreted with great caution due to great clinical heterogeneity, limited generalizability, and risk of bias. For meningioma patients, the ideal QOL questionnaire would present outcomes that can be easily measured, presented, and compared across studies. Existing scales can be the foundation upon which a comprehensive, standard, and simple meningioma-specific survey can be prospectively developed and validated.
Characterizing ruminal parameters in the context of sampling routine and feed efficiency is fundamental to understand the efficiency of feed utilization in the bovine. Therefore, we evaluated microbial and volatile fatty acid (VFA) profiles, rumen papillae epithelial and stratum corneum thickness and rumen pH (RpH) and temperature (RT) in feedlot cattle. In all, 48 cattle (32 steers plus 16 bulls), fed a high moisture corn and haylage-based ration, underwent a productive performance test to determine residual feed intake (RFI) using feed intake, growth, BW and composition traits. Rumen fluid was collected, then RpH and RT logger were inserted 5.5±1 days before slaughter. At slaughter, the logger was recovered and rumen fluid and rumen tissue were sampled. The relative daily time spent in specific RpH and RT ranges were determined. Polynomial regression analysis was used to characterize RpH and RT circadian patterns. Animals were divided into efficient and inefficient groups based on RFI to compare productive performance and ruminal parameters. Efficient animals consumed 1.8 kg/day less dry matter than inefficient cattle (P⩽0.05) while achieving the same productive performance (P⩾0.10). Ruminal bacteria population was higher (P⩽0.05) (7.6×1011v. 4.3×1011 copy number of 16S rRNA gene/ml rumen fluid) and methanogen population was lower (P⩽0.05) (2.3×109v. 4.9×109 copy number of 16S rRNA gene/ml rumen fluid) in efficient compared with inefficient cattle at slaughter with no differences (P⩾0.10) between samples collected on-farm. No differences (P⩾0.10) in rumen fluid VFA were also observed between feed efficiency groups either on-farm or at slaughter. However, increased (P⩽0.05) acetate, and decreased (P⩽0.05) propionate, butyrate, valerate and caproate concentrations were observed at slaughter compared with on-farm. Efficient had increased (P⩽0.05) rumen epithelium thickness (136 v. 126 µm) compared with inefficient cattle. Efficient animals also spent 318% and 93.2% more time (P⩽0.05) in acidotic (4.14% v. 1.30%) (pH⩽5.6) and optimal (5.6<pH<6.0) (8.53% v. 4.42%) RpH range compared with inefficient cattle. The circadian patterns revealed lower (P⩽0.05) RpH and no differences (P⩾0.10) in RT pre-, during, and post-prandial periods in efficient compared with inefficient cattle. In essence, superior feed efficiency in cattle seems linked to rumen features consistent with improved efficiency of feed utilization. Microbial abundance, rumen epithelial histomorphology, and RpH, may serve as indicators for feed efficiency in cattle. The divergences of assessments made on-farm and at slaughter should be considered in the development of proxies for feed efficiency.
The purpose of this study was to investigate whether significant difference exists on radiation dose delivered to organs at risks in megavoltage computed tomography (MVCT) verification using three predefined scanning modes, namely fine (2 mm), normal (4 mm) and coarse (6 mm). This will provide information for the imaging protocol of tomotherapy for the left breast.
Materials and methods
Organ doses were measured using thermoluminescent dosimeters (TLD-100) placed within a female Rando phantom for MVCT imaging. Kruskal–Wallis test was conducted with p<0·05 to evaluate the significant difference between the three MVCT scanning modes.
Statistically significant difference existed in organ absorbed dose between different scan mode selections (p<0·001). Relative to the normal scan selection (4 mm), the absorbed dose to the organs of interests can be scaled down by 0·7 and scaled up by 2·1 for coarse (6 mm) and fine scans (2 mm) respectively.
Optimisation of imaging protocols is of paramount importance to keep the radiation exposure ‘as low as reasonably achievable’. The recommendation of undergoing daily coarse mode for MVCT verification in breast tomotherapy not only mitigates the radiation exposure to normal tissues, but also trims the scan-acquisition time.
Evidence suggests that autism and schizophrenia share similarities in genetic, neuropsychological and behavioural aspects. Although both disorders are associated with theory of mind (ToM) impairments, a few studies have directly compared ToM between autism patients and schizophrenia patients. This study aimed to investigate to what extent high-functioning autism patients and schizophrenia patients share and differ in ToM performance.
Thirty high-functioning autism patients, 30 schizophrenia patients and 30 healthy individuals were recruited. Participants were matched in age, gender and estimated intelligence quotient. The verbal-based Faux Pas Task and the visual-based Yoni Task were utilised to examine first- and higher-order, affective and cognitive ToM. The task/item difficulty of two paradigms was examined using mixed model analyses of variance (ANOVAs). Multiple ANOVAs and mixed model ANOVAs were used to examine group differences in ToM.
The Faux Pas Task was more difficult than the Yoni Task. High-functioning autism patients showed more severely impaired verbal-based ToM in the Faux Pas Task, but shared similar visual-based ToM impairments in the Yoni Task with schizophrenia patients.
The findings that individuals with high-functioning autism shared similar but more severe impairments in verbal ToM than individuals with schizophrenia support the autism–schizophrenia continuum. The finding that verbal-based but not visual-based ToM was more impaired in high-functioning autism patients than schizophrenia patients could be attributable to the varied task/item difficulty between the two paradigms.
During 1990 we surveyed the southern sky using a multi-beam receiver at frequencies of 4850 and 843 MHz. The half-power beamwidths were 4 and 25 arcmin respectively. The finished surveys cover the declination range between +10 and −90 degrees declination, essentially complete in right ascension, an area of 7.30 steradians. Preliminary analysis of the 4850 MHz data indicates that we will achieve a five sigma flux density limit of about 30 mJy. We estimate that we will find between 80 000 and 90 000 new sources above this limit. This is a revised version of the paper presented at the Regional Meeting by the first four authors; the surveys now have been completed.
Parotid gland tumours are complex neoplasms with a broad histological range. The parotid gland is also a common site of face and scalp skin cancer metastases.
Parotidectomies performed by ENT department in the Gold Coast health district from 2006 to 2013.
A total of 158 specimens were examined. Of these, 53.80 per cent were benign and 46.20 per cent were malignant. Pleomorphic adenoma was the most common tumour (29.11 per cent), followed by cutaneous squamous cell carcinoma (23.42 per cent) and Warthin's tumour (12.03 per cent).
Metastatic squamous cell carcinoma accounted for a large proportion of parotid masses in our case series, reflecting the high prevalence of non-melanoma skin cancer in Australia. Primary parotid neoplasms had similar incidence rates to other studies.
In traditional transit timing variations (TTVs) analysis of multi-planetary systems, the individual TTVs are first derived from transit fitting and later modelled using n-body dynamic simulations to constrain planetary masses. We show that fitting simultaneously the transit light curves with the system dynamics (photo-dynamical model) increases the precision of the TTV measurements and helps constrain the system architecture. We exemplify the advantages of applying this photo-dynamical model to a multi-planetary system found in K2 data very close to 3:2 mean motion resonance, K2-19. In this case the period of the larger TTV variations (libration period) is much longer (>1.5 years) than the duration of the K2 observations (80 days). However, our method allows to detect the short period TTVs produced by the orbital conjunctions between the planets that in turn permits to uniquely characterise the system. Therefore, our method can be used to constrain the masses of near-resonant systems even when the full libration curve is not observed.
Some studies demonstrated that physical activity may have beneficial effect on cognitive function. The objective of the study was to estimate the association between physical activity and cognitive function in community-dwelling elderly Chinese in Hong Kong (HK) and Guangzhou (GZ).
In the neighborhood of HK and GZ, a convenience sample of 557 (260 in HK and 297 in GZ) older persons without dementia aged over 60 years (73.4 ± 6.5) was recruited. Physical activity was measured using a checklist. Information on physical activity participation, cognitive function, and other variables were collected. Multivariate linear regression analyses were performed to evaluate the association between physical activity and cognitive function.
Total number of physical activities showed significant association with the delayed recall test (p < 0.01) and category verbal fluency test (CVFT) (p < 0.01). However, with further adjustment for participation in intellectual activity, the coefficients were no longer statistically significant (p > 0.05)
Physical activity may not be associated with better cognitive function among elderly Chinese independently of other factors.
With the proportion of older adults in Hong Kong projected to double in size in the next 30 years, it is important to develop measures for detecting individuals in the earliest stage of Alzheimer's disease (AD, 0.5 in Clinical Dementia Rating, CDR). We tested the utility of a non-verbal prospective memory task (PM, ability to remember what one has to do when a specific event occurs in the future) as an early marker for AD in Hong Kong Chinese.
A large community dwelling sample of older adults who are healthy controls (CDR 0, N = 125), in the earliest stage of AD (CDR 0.5, N = 125), or with mild AD (CDR 1, N = 30) participated in this study. Their reaction time/accuracy data were analyzed by mixed-factor analyses of variance to compare the performance of the three CDR groups. Logistic regression analyses were performed to test the discriminative power of these measures for CDR 0 versus 0.5 participants.
Prospective memory performance declined as a function of AD severity: CDR 0 > CDR 0.5 > CDR 1, suggesting the effects of early-stage AD and AD progression on PM. After partialling out the variance explained by psychometric measures (e.g., ADAS-Cog), reaction time/accuracy measures that reflected the PM still significantly discriminated between CDR 0 versus 0.5 participants in most of the cases.
The effectiveness of PM measures in discriminating individuals in the earliest stage of AD from healthy older adults suggests that these measures should be further developed as tools for early-stage AD discrimination.
Hydrogels are an excellent scaffold structure for numerous applications in tissue engineering and regenerative medicine. In particular, they can be used as cell and drug carriers to deliver such therapeutic components directly and locally . Hydrogels can be injected and crosslinked in situ, reducing the need for risky invasive surgeries . In addition, hydrogels can mimic the natural extracellular matrix (ECM) environment, and allow one to control cellular and tissue functions as well as the transport of nutrients and bioactive molecules [3, 4].
Fumarate-based hydrogels are synthetic polymers, allowing flexible control of physical, mechanical, and degradative properties for a desired application . Fumaric acid, the fundamental component of these hydrogel scaffolds, is an unsaturated organic acid that is commonly found in the human body and can be metabolized through the Krebs cycle [5–7]. Polymer chains that contain fumarate units crosslink easily via the unsaturated double bonds and degrade through hydrolysis of the ester bonds in the fumarate group [6–9]. Furthermore, the biodegradable nature of these hydrogels allows neotissue ingrowth and eliminates the need for further surgery to remove the implanted scaffold [5, 10].
Efficient emergency and disaster response is challenged by environmental conditions exceeding test reagent storage and operating specifications. We assessed the effectiveness of vial and foil packaging in preserving point-of-care (POC) glucose and lactate test strip performance in humid conditions.
Glucose and lactate test strips in both packaging were exposed to mean relative humidity of 97.0 ± 1.1% in an environmental chamber for up to 168 hours. At defined time points, stressed strips were removed and tested in pairs with unstressed strips using whole blood samples spiked to glucose concentrations of 60, 100, and 250 mg/dL (n = 20 paired measurements per level). A Wilcoxon signed rank test was used to compare stressed and unstressed test strip measurements.
Stressed glucose and lactate test strip measurements differed significantly from unstressed strips, and were inconsistent between experimental trials. Median glucose paired difference was as high as 12.5 mg/dL at the high glucose test concentration. Median lactate bias was −0.2 mmol/L. Stressed strips from vial (3) and foil (7) packaging failed to produce results.
Both packaging designs appeared to protect glucose and lactate test strips for at least 1 week of high humidity stress. Documented strip failures revealed the need for improved manufacturing process. (Disaster Med Public Health Preparedness. 2014;0:1–7)
Molecular pathways underlying carcinogenesis: signal transduction
Eric W.-F. Lam, Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, London, UK,
Kyle W. Muir, Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, London, UK,
Chuay-Yeng Koo, Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, London, UK
Forkhead box (Fox) proteins belong to a superfamily of transcription factors that is characterized by a highly conserved “winged-helix” DNA-binding domain. Following the discovery of the first Fox transcription factor, FoxA, in Drosophila melanogaster, the identification of Fox genes has hitherto revealed at least 19 subclasses in humans (1). Fox proteins hold tight reins on determining cell fate, in particular cell proliferation, differentiation, and survival; thus it is predictable that the deregulation of these proteins has a major impact in the pathogenesis of cancer. Of the Fox proteins, the subfamilies FoxO, FoxM, FoxP, FoxC, and FoxA have been shown to participate in oncogenesis (2). As these Fox proteins recognize similar promoter elements on genomic DNA, they can potentially regulate the expression of overlapping gene targets. However, this chapter will focus on the involvement of the FoxO and FoxM1 proteins in cancer as there is an increasingly well-established and strong relationship between these two groups of Fox proteins through early tumorigenesis to advanced cancer progression and even chemotherapy response.
An overview of FoxO and FoxM1
The mammalian FoxO proteins, FoxO1, FoxO3a, FoxO4, and FoxO6, are downstream effectors of the PI3K-Akt (also called PKB) signaling pathway, a signaling cascade that is a focal point for deregulation in most cancers (3). The subcellular localization of FoxO, with the exception of the constitutively nuclear FoxO6, is typically dependent on the phosphorylation of these FoxO proteins by several key kinases, namely Akt/PKB, serum glucocorticord-induced protein kinase (SGK), CK1, IκB kinase (IKKβ), C-Jun N-terminal kinase (JNK), and p38 MAPK (4,5). It is well established that Akt-mediated phosphorylation of FoxO proteins results in cytoplasmic relocation and the consequent inability of these proteins to initiate transcription. Upon translocation to the nucleus, activated FoxO proteins are able to control cell fate by transcriptionally activating or repressing target genes by binding to the DNA of consensus sequences, and by interacting with other transcriptional co-activators such as p300/CREB-binding protein (CBP).
Sharper nanotips are required for application in nanoprobing systems due to a shrinking contact size with each new transistor technology node. We describe a two-step etching process to fabricate W nanotips with controllable tip dimensions. The first process is an optimized AC electrochemical etching in KOH to fabricate nanotips with a radius of curvature (ROC) down to 90 nm. This was followed by a secondary nanotip sharpening process by laser irradiation in KOH. High aspect ratio nanotips with ROC close to 20 nm were obtained. Finally we demonstrate the application of the fabricated nanotips for nanoprobing on advanced technology SRAM devices.