The diagnostic accuracy of telegeriatrics for the diagnosis of dementia via video conferencing

Introduction The suitability of video conferencing (VC) technology for clinical purposes relevant to geriatric medicine is still being established. This project aimed to determine the validity of the diagnosis of dementia via VC. Methods This was a multisite, noninferiority, prospective cohort study. Patients, aged 50 years and older, referred by their primary care physician for cognitive assessment, were assessed at 4 memory disorder clinics. All patients were assessed independently by 2 specialist physicians. They were allocated one face-to-face (FTF) assessment (Reference standard – usual clinical practice) and an additional assessment (either usual FTF assessment or a VC assessment) on the same day. Each specialist physician had access to the patient chart and the results of a battery of standardized cognitive assessments administered FTF by the clinic nurse. Percentage agreement (P0) and the weighted kappa statistic with linear weight (Kw) were used to assess inter-rater reliability across the 2 study groups on the diagnosis of dementia (cognition normal, impaired, or demented). Results The 205 patients were allocated to group: Videoconference (n = 100) or Standard practice (n = 105); 106 were men. The average age was 76 (SD 9, 51–95) and the average Standardized Mini-Mental State Examination Score was 23.9 (SD 4.7, 9–30). Agreement for the Videoconference group (P0= 0.71; Kw = 0.52; P < .0001) and agreement for the Standard Practice group (P0= 0.70; Kw = 0.50; P < .0001) were both statistically significant (P < .05). The summary kappa statistic of 0.51 (P = .84) indicated that VC was not inferior to FTF assessment. Conclusions Previous studies have shown that preliminary standardized assessment tools can be reliably administered and scored via VC. This study focused on the geriatric assessment component of the interview (interpretation of standardized assessments, taking a history and formulating a diagnosis by medical specialist) and identified high levels of agreement for diagnosing dementia. A model of service incorporating either local or remote administered standardized assessments, and remote specialist assessment, is a reliable process for enabling the diagnosis of dementia for isolated older adults.

Effects of oxygen on zonal marker expression in human articular chondrocytes

Articular cartilage is organized in depth zones with phenotypically distinct subpopulations of chondrocytes that are exposed to different oxygen tensions. Despite growing evidence of the critical role for oxygen in chondrogenesis, little is known about its effect on chondrocytes from different zones. This study evaluates zonal marker expression of human articular chondrocytes from different zones under various oxygen tensions. Chondrocytes isolated from full-thickness, superficial, and middle/deep cartilage from knee replacement surgeries were expanded and redifferentiated under hypoxic (5% O 2) or normoxic (20% O 2) conditions. Differentiation under hypoxia increased expression of hypoxia-inducible factors 1alpha and 2alpha and accumulation of extracellular matrix, particularly in middle/deep chondrocytes, and favored re-expression of proteoglycan 4 by superficial chondrocytes compared with middle/deep cells. Zone-dependent expression of clusterin varied with culture duration. These results demonstrate that zonal chondrocytes retain important phenotypic differences during in vitro cultivation, and that these characteristics can be improved by altering the oxygen environment. However, transcript levels for pleiotrophin, cartilage intermediate layer protein, and collagen type X were similar between zones, challenging their reliability as zonal markers for tissue-engineered cartilage from osteoarthritis patients. Key factors including oxygen tension and cell source should be considered to prescribe zone-specific properties to tissue-engineered cartilage. © 2012, Mary Ann Liebert, Inc.

Using optical coherence tomography for differential diagnosis of a pigmented choroidal lesion

Clinicians regularly face the confronting challenge of differentiating a choroidal naevus from a melanoma. Uveal naevi are a relatively common finding during routine eye examinations: a prevalence of 6.5 per cent has been reported.1 In contrast, malignant melanomata are uncommon, being found in six persons per million population, but they can have devastating implications and consequences.2 Differential diagnoses can be difficult to make with certainty; any additional information that can assist in this process is advantageous...

Clinical utility of mental state screening as a predictor of intellectual outcomes 6 months after diagnosis of type 1 diabetes

Background Screening tests of basic cognitive status or ‘mental state’ have been shown to predict mortality and functional outcomes in adults. This study examined the relationship between mental state and outcomes in children with type 1 diabetes. Objective We aimed to determine whether mental state at diagnosis predicts longer term cognitive function of children with a new diagnosis of type 1 diabetes. Methods Mental state of 87 patients presenting with newly diagnosed type 1 diabetes was assessed using the School-Years Screening Test for the Evaluation of Mental Status. Cognitive abilities were assessed 1 wk and 6 months postdiagnosis using standardized tests of attention, memory, and intelligence. Results Thirty-seven children (42.5%) had reduced mental state at diagnosis. Children with impaired mental state had poorer attention and memory in the week following diagnosis, and, after controlling for possible confounding factors, significantly lower IQ at 6 months compared to those with unimpaired mental state (p < 0.05). Conclusions Cognition is impaired acutely in a significant number of children presenting with newly diagnosed type 1 diabetes. Mental state screening is an effective method of identifying children at risk of ongoing cognitive difficulties in the days and months following diagnosis. Clinicians may consider mental state screening for all newly diagnosed diabetic children to identify those at risk of cognitive sequelae.

RCA method for fault diagnosis in digital substations of power systems

The authors present a Cause-Effect fault diagnosis model, which utilises the Root Cause Analysis approach and takes into account the technical features of a digital substation. The Dempster/Shafer evidence theory is used to integrate different types of fault information in the diagnosis model so as to implement a hierarchical, systematic and comprehensive diagnosis based on the logic relationship between the parent and child nodes such as transformer/circuit-breaker/transmission-line, and between the root and child causes. A real fault scenario is investigated in the case study to demonstrate the developed approach in diagnosing malfunction of protective relays and/or circuit breakers, miss or false alarms, and other commonly encountered faults at a modern digital substation.

Purine Nucleoside Phosphorylase mediated molecular chemotherapy and conventional chemotherapy: A tangible union against chemoresistant cancer

Background Late stage Ovarian Cancer is essentially incurable primarily due to late diagnosis and its inherent heterogeneity. Single agent treatments are inadequate and generally lead to severe side effects at therapeutic doses. It is crucial to develop clinically relevant novel combination regimens involving synergistic modalities that target a wider repertoire of cells and lead to lowered individual doses. Stemming from this premise, this is the first report of two- and three-way synergies between Adenovirus-mediated Purine Nucleoside Phosphorylase based gene directed enzyme prodrug therapy (PNP-GDEPT), docetaxel and/or carboplatin in multidrug-resistant ovarian cancer cells. Methods The effects of PNP-GDEPT on different cellular processes were determined using Shotgun Proteomics analyses. The in vitro cell growth inhibition in differentially treated drug resistant human ovarian cancer cell lines was established using a cell-viability assay. The extent of synergy, additivity, or antagonism between treatments was evaluated using CalcuSyn statistical analyses. The involvement of apoptosis and implicated proteins in effects of different treatments was established using flow cytometry based detection of M30 (an early marker of apoptosis), cell cycle analyses and finally western blot based analyses. Results Efficacy of the trimodal treatment was significantly greater than that achieved with bimodal- or individual treatments with potential for 10-50 fold dose reduction compared to that required for individual treatments. Of note was the marked enhancement in apoptosis that specifically accompanied the combinations that included PNP-GDEPT and accordingly correlated with a shift in the expression of anti- and pro-apoptotic proteins. PNP-GDEPT mediated enhancement of apoptosis was reinforced by cell cycle analyses. Proteomic analyses of PNP-GDEPT treated cells indicated a dowregulation of proteins involved in oncogenesis or cancer drug resistance in treated cells with accompanying upregulation of apoptotic- and tumour- suppressor proteins. Conclusion Inclusion of PNP-GDEPT in regular chemotherapy regimens can lead to significant enhancement of the cancer cell susceptibility to the combined treatment. Overall, these data will underpin the development of regimens that can benefit patients with late stage ovarian cancer leading to significantly improved efficacy and increased quality of life.

A new analytic approach for power system fault diagnosis employing the temporal information of alarm messages

Traditional analytic models for power system fault diagnosis are usually formulated as an unconstrained 0–1 integer programming problem. The key issue of the models is to seek the fault hypothesis that minimizes the discrepancy between the actual and the expected states of the concerned protective relays and circuit breakers. The temporal information of alarm messages has not been well utilized in these methods, and as a result, the diagnosis results may be not unique and hence indefinite, especially when complicated and multiple faults occur. In order to solve this problem, this paper presents a novel analytic model employing the temporal information of alarm messages along with the concept of related path. The temporal relationship among the actions of protective relays and circuit breakers, and the different protection configurations in a modern power system can be reasonably represented by the developed model, and therefore, the diagnosed results will be more definite under different circumstances of faults. Finally, an actual power system fault was served to verify the proposed method.

Utility of corneal confocal microscopy for assessing mild diabetic neuropathy: baseline findings of the LANDMark study

Background:  For those in the field of managing diabetic complications, the accurate diagnosis and monitoring of diabetic peripheral neuropathy (DPN) continues to be a challenge. Assessment of sub-basal corneal nerve morphology has recently shown promise as a novel ophthalmic marker for the detection of DPN. Methods:  Two hundred and thirty-one individuals with diabetes with predominantly mild or no neuropathy and 61 controls underwent evaluation of diabetic neuropathy symptom score, neuropathy disability score, testing with 10 g monofilament, quantitative sensory testing (warm, cold, vibration detection) and nerve conduction studies. Corneal nerve fibre length, branch density and tortuosity were measured using corneal confocal microscopy. Differences in corneal nerve morphology between individuals with and without DPN and controls were investigated using analysis of variance and correlations were determined between corneal morphology and established tests of, and risk factors for, DPN. Results:  Corneal nerve fibre length was significantly reduced in diabetic individuals with mild DPN compared with both controls (p < 0.001) and diabetic individuals without DPN (p = 0.012). Corneal nerve branch density was significantly reduced in individuals with mild DPN compared with controls (p = 0.032). Corneal nerve fibre tortuosity did not show significant differences. Corneal nerve fibre length and corneal nerve branch density showed modest correlations to most measures of neuropathy, with the strongest correlations to nerve conduction study parameters (r = 0.15 to 0.25). Corneal nerve fibre tortuosity showed only a weak correlation to the vibration detection threshold. Corneal nerve fibre length was inversely correlated to glycated haemoglobin (r = -0.24) and duration of diabetes (r = -0.20). Conclusion:  Assessment of corneal nerve morphology is a non-invasive, rapid test capable of showing differences between individuals with and without DPN. Corneal nerve fibre length shows the strongest associations with other diagnostic tests of neuropathy and with established risk factors for neuropathy.

Analysis of genome survey sequences and SSR marker development for Siamese Mud Carp, Henicorhynchus siamensis, using 454 Pyrosequencing

Siamese mud carp (Henichorynchus siamensis) is a freshwater teleost of high economic importance in the Mekong River Basin. However, genetic data relevant for delineating wild stocks for management purposes currently are limited for this species. Here, we used 454 pyrosequencing to generate a partial genome survey sequence (GSS) dataset to develop simple sequence repeat (SSR) markers from H. siamensis genomic DNA. Data generated included a total of 65,954 sequence reads with average length of 264 nucleotides, of which 2.79% contain SSR motifs. Based on GSS-BLASTx results, 10.5% of contigs and 8.1% singletons possessed significant similarity (E value < 10–5) with the majority matching well to reported fish sequences. KEGG analysis identified several metabolic pathways that provide insights into specific potential roles and functions of sequences involved in molecular processes in H. siamensis. Top protein domains detected included reverse transcriptase and the top putative functional transcript identified was an ORF2-encoded protein. One thousand eight hundred and thirty seven sequences containing SSR motifs were identified, of which 422 qualified for primer design and eight polymorphic loci have been tested with average observed and expected heterozygosity estimated at 0.75 and 0.83, respectively. Regardless of their relative levels of polymorphism and heterozygosity, microsatellite loci developed here are suitable for further population genetic studies in H. siamensis and may also be applicable to other related taxa.

Kallikrein 14 is down-regulated by androgen receptor signalling and harbours genetic variation that is associated with prostate tumour aggressiveness

Kallikrein 14 (KLK14) has been proposed as a useful prognostic marker in prostate cancer, with expression reported to be associated with tumour characteristics such as higher stage and Gleason score. KLK14 tumour expression has also shown the potential to predict prostate cancer patients at risk of disease recurrence after radical prostatectomy. The KLKs are a remarkably hormone-responsive family of genes, although detailed studies of androgen regulation of KLK14 in prostate cancer have not been undertaken to date. Using in vitro studies, we have demonstrated that unlike many other prostatic KLK genes that are strictly androgen responsive, KLK14 is more broadly expressed and inversely androgen regulated in prostate cancer cells. Given these results and evidence that KLK14 may play a role in prostate cancer prognosis, we also investigated whether common genetic variants in the KLK14 locus are associated with risk and/or aggressiveness of prostate cancer in approximately 1200 prostate cancer cases and 1300 male controls. Of 41 single nucleotide polymorphisms assessed, three were associated with higher Gleason score (≥7): rs17728459 and rs4802765, both located upstream of KLK14, and rs35287116, which encodes a p.Gln33Arg substitution in the KLK14 signal peptide region. Our findings provide further support for KLK14 as a marker of prognosis in prostate cancer.

Pregnancy as public property: The experience of couples following diagnosis of a foetal anomaly

Background: Pregnant women find themselves subject to comments and questions from people in public areas. Normally, becoming ‘public property’ is considered friendly and is relatively easy for pregnant women to deal with. However, following diagnosis of a fetal anomaly, the experience of being public property can exacerbate the emotional turmoil experienced by couples. Original research question: What is the experience of couples who continue pregnancy following the diagnosis of a fetal anomaly? Method: The study used an interpretive design informed by Merleau-Ponty and this paper reports on a subset of findings. Thirty-one interviews with pregnant women and their partners were undertaken following the diagnosis of a serious or lethal fetal anomaly. Women were between 25 and 38 weeks gestation at the time of their first interview. The non-directive interviews were audiotaped, transcribed verbatim and the transcripts were thematically analysed. Findings: A prominent theme that emerged during data analysis was that pregnancy is embodied therefore physically evident and ‘public’. Women found it difficult to deal with being public property when the fetus had a serious or lethal anomaly. Some women avoided social situations; others did not disclose the fetal condition but gave minimal or avoidant answers to minimise distress to themselves and others. The male participants were not visibly pregnant and they could continue life in public without being subject to the public’s gaze, but they were very aware and concerned about its impact on their partner. Conclusion: The public tend to assume that pregnancy is normal and will produce a healthy baby. This becomes problematic for women who have a fetus with an anomaly. Women use strategies to help them cope with becoming public property during pregnancy. Midwives can play an important role in reducing the negative consequences of a woman becoming public property following the diagnosis of a fetal anomaly.

Circulating tumour cells, their role in metastasis and their clinical utility in lung cancer

Circulating tumour cells (CTCs) have attracted much recent interest in cancer research as a potential biomarker and as a means of studying the process of metastasis. It has long been understood that metastasis is a hallmark of malignancy, and conceptual theories on the basis of metastasis from the nineteenth century foretold the existence of a tumour "seed" which is capable of establishing discrete tumours in the "soil" of distant organs. This prescient "seed and soil" hypothesis accurately predicted the existence of CTCs; microscopic tumour fragments in the blood, at least some of which are capable of forming metastases. However, it is only in recent years that reliable, reproducible methods of CTC detection and analysis have been developed. To date, the majority of studies have employed the CellSearch™ system (Veridex LLC), which is an immunomagnetic purification method. Other promising techniques include microfluidic filters, isolation of tumour cells by size using microporous polycarbonate filters and flow cytometry-based approaches. While many challenges still exist, the detection of CTCs in blood is becoming increasingly feasible, giving rise to some tantalizing questions about the use of CTCs as a potential biomarker. CTC enumeration has been used to guide prognosis in patients with metastatic disease, and to act as a surrogate marker for disease response during therapy. Other possible uses for CTC detection include prognostication in early stage patients, identifying patients requiring adjuvant therapy, or in surveillance, for the detection of relapsing disease. Another exciting possible use for CTC detection assays is the molecular and genetic characterization of CTCs to act as a "liquid biopsy" representative of the primary tumour. Indeed it has already been demonstrated that it is possible to detect HER2, KRAS and EGFR mutation status in breast, colon and lung cancer CTCs respectively. In the course of this review, we shall discuss the biology of CTCs and their role in metastagenesis, the most commonly used techniques for their detection and the evidence to date of their clinical utility, with particular reference to lung cancer.