The effect of multimodal and enriched feedback on SMR-BCI performance.

OBJECTIVE: This study investigated the effect of multimodal (visual and auditory) continuous feedback with information about the uncertainty of the input signal on motor imagery based BCI performance. A liquid floating through a visualization of a funnel (funnel feedback) provided enriched visual or enriched multimodal feedback. METHODS: In a between subject design 30 healthy SMR-BCI naive participants were provided with either conventional bar feedback (CB), or visual funnel feedback (UF), or multimodal (visual and auditory) funnel feedback (MF). Subjects were required to imagine left and right hand movement and were trained to control the SMR based BCI for five sessions on separate days. RESULTS: Feedback accuracy varied largely between participants. The MF feedback lead to a significantly better performance in session 1 as compared to the CB feedback and could significantly enhance motivation and minimize frustration in BCI use across the five training sessions. CONCLUSION: The present study demonstrates that the BCI funnel feedback allows participants to modulate sensorimotor EEG rhythms. Participants were able to control the BCI with the funnel feedback with better performance during the initial session and less frustration compared to the CB feedback. SIGNIFICANCE: The multimodal funnel feedback provides an alternative to the conventional cursorbar feedback for training subjects to modulate their sensorimotor rhythms.

ERK5 signalling in prostate cancer promotes an invasive phenotype.

BACKGROUND: Aberrant mitogen/extracellular signal-regulated kinase 5 (MEK5)-extracellular signal-regulated protein kinase 5 (ERK5)-mediated signalling has been implicated in a number of tumour types including prostate cancer (PCa). The molecular basis of ERK5-driven carcinogenesis and its clinical relevance remain to be fully characterised. METHODS: Modulation of ERK5 expression or function in human PCa PC3 and PC3-ERK5 (stably transfected with ERK5) cells was performed using siRNA-mediated knockdown or the MEK inhibitor PD18435 respectively. In vitro significance of ERK5 signalling was assessed by assays for proliferation, motility, invasion and invadopodia. Expression of matrix metalloproteinases/tissue inhibitors of metalloproteases was determined by Q-RT-PCR. Extracellular signal-regulated protein kinase 5 expression in primary and metastatic PCa was examined using immunohistochemistry. RESULTS: Reduction of ERK5 expression or signalling significantly inhibited the motility and invasive capability of PC3 cells. Extracellular signal-regulated protein kinase 5-mediated signalling significantly promoted formation of in vivo metastasis in an orthotopic PCa model (P<0.05). Invadopodia formation was also enhanced by forced ERK5 expression in PC3 cells. Furthermore, in metastatic PCa, nuclear ERK5 immunoreactivity was significantly upregulated when compared with benign prostatic hyperplasia and primary PCa (P=0.013 and P<0.0001, respectively). CONCLUSION: Our in vitro, in vivo and clinical data support an important role for the MEK5-ERK5 signalling pathway in invasive PCa, which represents a potential target for therapy in primary and metastatic PCa.

Head and neck cancer in the UK: what is expected of cytopathology?

OBJECTIVE: This review highlights the role of cytopathology in cancer management within UK Head and Neck Cancer Networks and informs on the issues raised by recent UK Department of Health documents and other UK professional guidance. UK guidance requires the formal involvement of cytopathologists within multidisciplinary cancer teams, with medical and non-medical cytopathology staff setting up and running rapid access lump clinics, and support for image-guided fine needle aspiration cytology (FNAC) services. UK guidance also makes recommendations for training, resources and quality control. This review also highlights the resource gap between best practice evidence-based guidance for head and neck (HN) cancer services and existing UK provision for cytopathology, as evidenced by lack of availability of experienced staff and adequacy of training and quality control (QC). Finally, it stresses the importance in the UK of the Royal College of Pathologists' guidance, which defines the need for training, the experience needed for new consultants, the requirements for audit and QC. The implications for the additional resources required for HN cancer cytopathology services are discussed. Recent professional guidance specifying the provision of HN cancer services in the UK includes a cytopathology service for cancer networks, such as rapid access FNAC clinics. Although these clinics already operate in some institutions, there are many institutions where they do not and where the provision of cytopathology services would have to be restructured. This would need the support of local cancer networks and their acceptance of the detailed requirements for cytopathology, including resources, training and QC. The standards are not defined locally, as Strategic Health Authorities and Primary Care Trusts have been instructed by the Department of Health to support, invest and implement them.

Carers' perceptions of pain in people with dementia: a grounded theory approach.

The purpose of this Grounded Theory based study was to add to the limited understanding about the perception and observation of pain by the formal and informal carers of people with dementia. Thirty-one carers talked about how they know when their person with dementia has pain. Findings showed there is no one set of signs or behaviours that indicate pain in all people with dementia. However, a common pain assessment process amongst carers involved being able to detect deviation from normal behaviours based upon their intimate knowledge of what is normal for their person. A central hypothesis was thus generated from the data that considered that effective pain assessment for people with dementia is dependent on carers having an intimate knowledge of the individual's normal state of being with dementia. Implications for nursing practice are discussed.

Quantification of relative afferent pupillary defects induced by posterior sub-Tenon's, peribulbar, and retrobulbar anaesthetics.

AIMS: The effect of local anaesthetics on optic nerve function can be investigated by quantifying the relative afferent pupillary defect (RAPD). METHODS: The study compared the depth of induced RAPD following posterior sub-Tenon's, retrobulbar, and peribulbar local anaesthetics using crossed polarising filters before cataract surgery (time 1 = 5 minutes), immediately after surgery (time 2 = 42 minutes (av)), and once again on the ward (time 3 = 107 minutes (av)). RESULTS: All patients developed a RAPD. There was no significant difference in the depth of RAPD between the groups at any one time period. The peribulbar group had a significantly steeper decay in RAPD from time 1 to time 2 (p = 0.014). This effect was reduced when the shorter operation time for this group was entered as a cofactor (p = 0.063). By time 3 the RAPDs for all groups had decayed similarly so that no differences could be detected. CONCLUSION: All three anaesthetic methods caused a similar level of disruption to optic nerve conduction immediately following administration and at the time of day case discharge.

Randomized controlled trial of a drug regimen that includes ciprofloxacin for the treatment of pulmonary tuberculosis.

The fluoroquinolones are promising new antituberculous agents. A randomized controlled trial of 200 adult patients with sputum smear-positive pulmonary tuberculosis was conducted in Tanzania. Patients received either a trial regimen (HRC) consisting of isoniazid (300 mg), rifampin (600 mg), and ciprofloxacin (750 mg) or a control regimen (HRZE) consisting of isoniazid (300 mg), rifampin (600 mg), pyrazinamide (25 mg/kg), and ethambutol (15 mg/kg). The 168 evaluable patients all had negative smears and cultures by month 6, but the time to conversion to negativity was longer for the HRC group than for the HRZE group because of the poor response of patients infected with human immunodeficiency virus (HIV) to the HRC regimen. Relapse was more frequent in the HRC group. The sterilizing activity of ciprofloxacin does not appear to be equal to that of the combination of pyrazinamide and ethambutol, but the difference in outcome was significant only among HIV-infected patients.

Nutritional status and weight gain in patients with pulmonary tuberculosis in Tanzania.

We assessed nutritional status in 200 adult Tanzanian patients with smear-positive pulmonary tuberculosis before, during, and after 6 months of tuberculosis treatment; 148 patients (74%) were successfully followed for 12 months. Marked nutritional impairment was present on admission: 77% of males and 58% of females had a body mass index (BMI) below 18.5; approximately one-fifth had BMI < 16.0. The length of hospital stay and gender, rather than microbiological response, were the major determinants of weight gain during treatment. Patients infected with human immunodeficiency virus (HIV) gained more weight than uninfected patients. Most patients lost weight after completing treatment and returning home. At 12 months, 32% of male and 19% of female patients considered cured of tuberculosis had BMI < 18.5. It is concluded that patients with tuberculosis from this area of Tanzania frequently have evidence of malnutrition both before and after treatment for tuberculosis. Weight gain during therapy appeared to be an unreliable indicator of overall treatment response. However, the results also demonstrated that nutritional rehabilitation can be successfully achieved even in HIV-positive tuberculosis patients and in patients with a suboptimal response to therapy.

PIP: The authors assessed nutritional status in 200 adult Tanzanian patients with smear-positive pulmonary tuberculosis (TB) before, during, and after 6 months of TB treatment. 148 patients were successfully followed for 12 months. Upon admission, 77% of males and 58% of females had a body mass index (BMI) below 18.5, with about 20% having BMI less than 16.0. Most patients lost weight after completing treatment and returning home. At 12 months, 32% of male and 19% of female patients considered cured of TB had BMI less than 18.5. The length of hospital stay and gender, rather than microbiological response, were the major determinants of weight gain during treatment. Patients infected with HIV gained more weight than uninfected patients. The authors conclude that TB patients in Tanzania frequently have evidence of malnutrition both before and after treatment for TB. Weight gain during therapy appeared to be an unreliable indicator of overall treatment response. The study also demonstrated that nutritional rehabilitation can be successfully achieved even in HIV-positive TB patients and in patients with a suboptimal response to therapy.

Effect of indomethacin on blood pressure control during treatment with nitrendipine.

This study tested the hypothesis that treatment with a nonsteroidal anti-inflammatory drug will not alter the hypotensive effect of a dihydropyridine calcium channel antagonist. Fifteen essential hypertensives (ages 58-80 years) had a supine diastolic blood pressure (DBP) < 100 mmHg after 4 weeks monotherapy with nitrendipine 5-20 mg twice daily. They entered a double-blind randomised crossover study in which the addition of indomethacin 25 mg three times daily was compared with placebo in treatment phases each of 4 weeks duration. Subjects were seen weekly and measurements in the last 2 weeks of each phase were compared. Supine blood pressure (mean +/- SE) was higher in the indomethacin phase (158 +/- 4/80 +/- 2) than in the placebo phase (154 +/- 4/76 +/- 3) (p < 0.01 for DBP). In 6/15 (40%) of subjects the increase in supine diastolic blood pressure with indomethacin was > 5 mmHg. Plasma urea was also increased in the indomethacin phase: 7.6 +/- 0.6 mmol/l compared with placebo: 6.3 +/- 0.5 mmol/l (p < 0.001). The study has demonstrated that concurrent treatment with the NSAID indomethacin impairs the blood pressure lowering effect of the dihydropyridine calcium channel antagonist nitrendipine. This increase in blood pressure with indomethacin in subjects treated with nitrendipine may represent either an independent pressor effect of indomethacin or a reduced vasodilator prostanoid contribution to the hypotensive effect of nitrendipine. This blood pressure increase may be sufficient to interfere significantly with clinical blood pressure control in some subjects.

Early bactericidal and sterilizing activities of ciprofloxacin in pulmonary tuberculosis.

The early bactericidal and sterilizing activities of ciprofloxacin were evaluated in the treatment of adult patients with smear positive pulmonary tuberculosis. Two randomized prospective studies were performed in Northern Tanzania. In study 1, ten patients received either 750 mg ciprofloxacin or 300 ng isoniazid daily for 7 days. Counts of colony-forming units (cfu) of Mycobacterium tuberculosis in early morning sputum were performed. In study 2, twenty patients received either a standard regimen of rifampin (R), isoniazid (H), pyrazinamide (Z), and ethambutol (E) (regimen HRZE) or a trial regimen of ciprofloxacin (C), isoniazid (H), and rifampin (R) (regimen HRC). Sputum colony counts were performed for 8 wk. Patients were tested for antibodies to human immunodeficiency virus (HIV)-1. The results demonstrate that ciprofloxacin alone has useful early bactericidal activity, resulting in a mean daily fall of 0.20 log10cfu/ml/day during 7 days compared with 0.25 log10cfu/ml/day for isoniazid. When HRZE and HRC regimens were compared, the HRC regimen appeared to be inferior in its sterilizing ability, with a culture conversion rate of 67% at 2 months compared with 100% for HRZE. The difference in outcome was most marked in HIV-1 positive patients. The role of ciprofloxacin in combination regimens may be as a bactericidal rather than a sterilizing agent.

The general practitioner as an effective counsellor.

Counselling is a therapeutic process that takes place during structured conversations between counsellor and client. General practitioners have the opportunity to gain clinical, psychological and social insights about their patients and their patients' problems. Personal and professional preparation must be made to enhance this role.

Calcium oxalate microcrystalline-associated arthritis in end-stage renal disease.

Chronic renal failure is known to be associated with secondary hyperoxalemia and the deposition of calcium oxalate in visceral organs, bones, and cartilage. We report the identification of calcium oxalate crystals in the synovial fluid of three patients with chronic renal failure. In one patient, calcium oxalate crystals were also identified within synovium and cartilage. Crystals were pleomorphic and bipyramidal. Some crystals were rod-like and had positive birefringence, thus tending to be confused with calcium pyrophosphate dihydrate when observed with only compensated polarized light microscopy. In one patients asymptomatic effusions were associated with joint capsule calcification, but otherwise normal knee radiographs. The other two patients had bilateral knee pain, one having coexistent features of osteoarthritis and the other chondrocalcinosis. Samples of proliferative synovium, joint capsule, and cartilage from the patient with chondrocalcinosis showed abundant calcium oxalate crystals, and not calcium pyrophosphate dihydrate or calcium hydroxyapatite. Thus, radiographically typical chondrocalcinosis may be due to calcium oxalate. Joint disease in chronic renal failure may be associated with calcium oxalate as well as the previously recognized apatite deposition.

Effects of phosphate limitation of growth on the cell-wall and lipid composition of Saccharomyces cerevisiae.

The phosphorus content of phosphate-limited Saccharomyces cerevisiae was only 71% of that of non-limited yeast. Walls prepared from phosphate-limited cells contained slightly less phosphorus than control walls. No evidence was obtained for the presence in these walls of uronic acid or succinyl residues. The carbohydrate content of walls of phosphate-limited yeast was less than that of non-limited walls, and this was reflected in a decreased glucan content. There was only a slight decrease in glucosamine content while the protein content increased. The major change in the lipid composition of phosphate-limited yeast was a decrease in both sterol esters and triacylglycerols. There was a decrease in total lipid content, but increased production of phosphatidylethanolamine and phosphatidylcholine. The phosphatidylserine content was decreased. These results suggest that there are fewer intracellular low-density vesicles in phosphate-limited yeast.