Cortical depth dependent functional responses in humans at 7T: improved specificity with 3D GRASE

Ultra high fields (7T and above) allow functional imaging with high contrast-to-noise ratios and improved spatial resolution. This, along with improved hardware and imaging techniques, allow investigating columnar and laminar functional responses. Using gradient-echo (GE) (T2* weighted) based sequences, layer specific responses have been recorded from human (and animal) primary visual areas. However, their increased sensitivity to large surface veins potentially clouds detecting and interpreting layer specific responses. Conversely, spin-echo (SE) (T2 weighted) sequences are less sensitive to large veins and have been used to map cortical columns in humans. T2 weighted 3D GRASE with inner volume selection provides high isotropic resolution over extended volumes, overcoming some of the many technical limitations of conventional 2D SE-EPI, whereby making layer specific investigations feasible. Further, the demonstration of columnar level specificity with 3D GRASE, despite contributions from both stimulated echoes and conventional T2 contrast, has made it an attractive alternative over 2D SE-EPI. Here, we assess the spatial specificity of cortical depth dependent 3D GRASE functional responses in human V1 and hMT by comparing it to GE responses. In doing so we demonstrate that 3D GRASE is less sensitive to contributions from large veins in superficial layers, while showing increased specificity (functional tuning) throughout the cortex compared to GE

Risk-Sensitive Mean-Field Type Control under Partial Observation

We establish a stochastic maximum principle (SMP) for control problems of partially observed diffusions of mean-field type with risk-sensitive performance functionals.Comment: arXiv admin note: text overlap with arXiv:1404.144

Postoperative IOP prophylaxis practice following uncomplicated cataract surgery: a UK-wide consultant survey

BACKGROUND: In order to minimise postoperative intraocular pressure (IOP) rise, after routine uncomplicated cataract surgery, prophylaxis may be adopted. Currently, there are no specific guidelines in this regard resulting in wide variation in practice across the UK. We sought to document these variations through a questionnaire survey. METHODS: A questionnaire was sent to all consultant ophthalmic surgeons in the UK. RESULTS: 62.6% of surgeons did not use any IOP lowering agents. 37.4% surgeons routinely prescribed some form of medication. The majority (86.8%) used oral diamox. 20.6% of surgeons said they based their practice on evidence, 43.3% on personal experience, and 17.6% on unit policy. Surprisingly, among the two groups of surgeons (those who gave routine prophylaxis, and those who did not) the percentages of surgeons quoting personal experience, unit policy, or presence of evidence was strikingly similar. The timing of the first postoperative IOP check varied from the same day to beyond 2 weeks. Only 20.2% of surgeons had ever seen an adverse event related to IOP rise; this complication is thus very rare. CONCLUSION: This survey highlights a wide variation in the practice and postoperative management of phacoemulsification cataract surgery. What is very striking is that there is a similar proportion of surgeons in the diametrically opposite groups (those who give or do not give routine IOP lowering prophylaxis) who believe that there practice is evidence based. The merits of this study suggests that consideration must be given to drafting a uniform guideline in this area of practice

Homeopathic medical practice: Long-term results of a cohort study with 3981 patients

BACKGROUND: On the range of diagnoses, course of treatment, and long-term outcome in patients who chose to receive homeopathic medical treatment very little is known. We investigated homeopathic practice in an industrialized country under everyday conditions. METHODS: In a prospective, multicentre cohort study with 103 primary care practices with additional specialisation in homeopathy in Germany and Switzerland, data from all patients (age >1 year) consulting the physician for the first time were observed. The main outcome measures were: Patient and physician assessments (numeric rating scales from 0 to 10) and quality of life at baseline, and after 3, 12, and 24 months. RESULTS: A total of 3,981 patients were studied including 2,851 adults (29% men, mean age 42.5 ± 13.1 years; 71% women, 39.9 ± 12.4 years) and 1,130 children (52% boys, 6.5 ± 3.9 years; 48% girls, 7.0 ± 4.3 years). Ninety-seven percent of all diagnoses were chronic with an average duration of 8.8 ± 8 years. The most frequent diagnoses were allergic rhinitis in men, headache in women, and atopic dermatitis in children. Disease severity decreased significantly (p < 0.001) between baseline and 24 months (adults from 6.2 ± 1.7 to 3.0 ± 2.2; children from 6.1 ± 1.8 to 2.2 ± 1.9). Physicians' assessments yielded similar results. For adults and young children, major improvements were observed for quality of life, whereas no changes were seen in adolescents. Younger age and more severe disease at baseline were factors predictive of better therapeutic success. CONCLUSION: Disease severity and quality of life demonstrated marked and sustained improvements following homeopathic treatment period. Our findings indicate that homeopathic medical therapy may play a beneficial role in the long-term care of patients with chronic diseases

Simultaneous intra/extravascular administration of antiproliferative agents as a new strategy to inhibit restenosis: The peak of reactive cell proliferation as a hallmark for the duration of the treatment

BACKGROUND: Strictly intravascular approaches for the treatment of postangioplasty restenosis are effective in the intima and the inner parts of the media but may be insufficient to control redundant pathways in the more outer parts of the media and the adventitia. An inverse situation may occur subsequently to a strictly extravascular approach, like the recently suggested pericardial approach in pigs. We hypothesized that simultaneous intra/extravascular administration of anti-restenotic agents inhibits restenosis by blocking all stimulatory pathways in the entire arterial wall. METHODS: Fresh hearts of 25 domestic pigs were obtained from a local slaughterhouse. Left anterior descending coronary arteries (LAD) were harvested, cut into cylindric 5 mm segments, and cultured as ex vivo porcine organ cultures (POCs). After 9 bar ballooning simultaneous intra/extravascular administration of high dose diltiazem (50 μg/mL) was carried out for a period of 1, 2, 3, 4, 5, 6, and 7 days. At day 7 and 28 proliferative activity (BrdU), neointimal thickening, and staining against smooth muscle α-actin and vWF was analysed. RESULTS: 7 days after ballooning administration of diltiazem for 4, 5, 6, and 7 days inhibited reactive cell proliferation by more than 50% (n.s.) as compared to control, 28 days after ballooning administration for 6 and 7 days inhibited neointimal thickening by more than 75% (p < 0.05). Simultaneous intra/extravascular administration of high dose diltiazem did not affect the expression of vWF in endothelial cells or smooth muscle α-actin in smooth muscle cells. CONCLUSIONS: Simultaneous intra/extravascular administration of high dose diltiazem (50 μg/mL) has to be maintained for at least 6 days to achieve a significant inhibition of neointimal thickening. The data demonstrate the importance of the maximal reactive cell proliferation (= day 7 in the POC-model) for the calculation of the duration of the treatment period

Towards a General Theory of Neural Computation Based on Prediction by Single Neurons

Although there has been tremendous progress in understanding the mechanics of the nervous system, there has not been a general theory of its computational function. Here I present a theory that relates the established biophysical properties of single generic neurons to principles of Bayesian probability theory, reinforcement learning and efficient coding. I suggest that this theory addresses the general computational problem facing the nervous system. Each neuron is proposed to mirror the function of the whole system in learning to predict aspects of the world related to future reward. According to the model, a typical neuron receives current information about the state of the world from a subset of its excitatory synaptic inputs, and prior information from its other inputs. Prior information would be contributed by synaptic inputs representing distinct regions of space, and by different types of non-synaptic, voltage-regulated channels representing distinct periods of the past. The neuron's membrane voltage is proposed to signal the difference between current and prior information (“prediction error” or “surprise”). A neuron would apply a Hebbian plasticity rule to select those excitatory inputs that are the most closely correlated with reward but are the least predictable, since unpredictable inputs provide the neuron with the most “new” information about future reward. To minimize the error in its predictions and to respond only when excitation is “new and surprising,” the neuron selects amongst its prior information sources through an anti-Hebbian rule. The unique inputs of a mature neuron would therefore result from learning about spatial and temporal patterns in its local environment, and by extension, the external world. Thus the theory describes how the structure of the mature nervous system could reflect the structure of the external world, and how the complexity and intelligence of the system might develop from a population of undifferentiated neurons, each implementing similar learning algorithms

Age-related decline of peripheral visual processing: the role of eye movements

Earlier work suggests that the area of space from which useful visual information can be extracted (useful field of view, UFoV) shrinks in old age. We investigated whether this shrinkage, documented previously with a visual search task, extends to a bimanual tracking task. Young and elderly subjects executed two concurrent tracking tasks with their right and left arms. The separation between tracking displays varied from 3 to 35 cm. Subjects were asked to fixate straight ahead (condition FIX) or were free to move their eyes (condition FREE). Eye position was registered. In FREE, young subjects tracked equally well at all display separations. Elderly subjects produced higher tracking errors, and the difference between age groups increased with display separation. Eye movements were comparable across age groups. In FIX, elderly and young subjects tracked less well at large display separations. Seniors again produced higher tracking errors in FIX, but the difference between age groups did not increase reliably with display separation. However, older subjects produced a substantial number of illicit saccades, and when the effect of those saccades was factored out, the difference between young and older subjects’ tracking did increase significantly with display separation in FIX. We conclude that the age-related shrinkage of UFoV, previously documented with a visual search task, is observable with a manual tracking task as well. Older subjects seem to partly compensate their deficit by illicit saccades. Since the deficit is similar in both conditions, it may be located downstream from the convergence of retinal and oculomotor signals

Bupropion for the treatment of apathy in Huntington's disease:A multicenter, randomised, double-blind, placebo-controlled, prospective crossover trial

OBJECTIVE:To evaluate the efficacy and safety of bupropion in the treatment of apathy in Huntington's disease (HD). METHODS:In this phase 2b multicentre, double-blind, placebo-controlled crossover trial, individuals with HD and clinical signs of apathy according to the Structured Clinical Interview for Apathy-Dementia (SCIA-D), but not depression (n = 40) were randomized to receive either bupropion 150/300mg or placebo daily for 10 weeks. The primary outcome parameter was a significant change of the Apathy Evaluation Scale (AES) score after ten weeks of treatment as judged by an informant (AES-I) living in close proximity with the study participant. The secondary outcome parameters included changes of 1. AES scores determined by the patient (AES-S) or the clinical investigator (AES-C), 2. psychiatric symptoms (NPI, HADS-SIS, UHDRS-Behavior), 3. cognitive performance (SDMT, Stroop, VFT, MMSE), 4. motor symptoms (UHDRS-Motor), 5. activities of daily function (TFC, UHDRS-Function), and 6. caregiver distress (NPI-D). In addition, we investigated the effect of bupropion on brain structure as well as brain responses and functional connectivity during reward processing in a gambling task using magnetic resonance imaging (MRI). RESULTS:At baseline, there were no significant treatment group differences in the clinical primary and secondary outcome parameters. At endpoint, there was no statistically significant difference between treatment groups for all clinical primary and secondary outcome variables. Study participation, irrespective of the intervention, lessened symptoms of apathy according to the informant and the clinical investigator. CONCLUSION:Bupropion does not alleviate apathy in HD. However, study participation/placebo effects were observed, which document the need for carefully controlled trials when investigating therapeutic interventions for the neuropsychiatric symptoms of HD. TRIAL REGISTRATION:ClinicalTrials.gov 01914965

The diagnosis and management of patients with idiopathic osteolysis

Idiopathic osteolysis or disappearing bone disease is a condition characterized by the spontaneous onset of rapid destruction and resorption of a single bone or multiple bones. Disappearing bone disorder is a disease of several diagnostic types. We are presenting three patients with osteolysis who have different underlying pathological features. Detailed phenotypic assessment, radiologic and CT scanning, and histological and genetic testing were the baseline diagnostic tools utilized for diagnosis of each osteolysis syndrome. The first patient was found to have Gorham-Stout syndrome (non-heritable). The complete destruction of pelvic bones associated with aggressive upward extension to adjacent bones (vertebral column and skull base) was notable and skeletal angiomatosis was detected. The second patient showed severe and aggressive non-hereditary multicentric osteolysis with bilateral destruction of the hip bones and the tarsal bones as well as a congenital unilateral solitary kidney and nephropathy. The third patient was phenotypically and genotypically compatible with Winchester syndrome resulting in multicentric osteolysis (autosomal recessive). Proven mutation of the (MMP2-Gen) was detected in this third patient that was associated with 3MCC deficiency (3-Methylcrontonyl CoA Carboxylase deficiency). The correct diagnoses in our 3 patients required the exclusion of malignant osteoclastic tumours, inflammatory disorders of bone, vascular disease, and neurogenic arthropathies using history, physical exam, and appropriate testing and imaging. This review demonstrates how to evaluate and treat these complex and difficult patients. Lastly, we described the various management procedures and treatments utilized for these patients

Anonymisation of geographical distance matrices via Lipschitz embedding

BACKGROUND: Anonymisation of spatially referenced data has received increasing attention in recent years. Whereas the research focus has been on the anonymisation of point locations, the disclosure risk arising from the publishing of inter-point distances and corresponding anonymisation methods have not been studied systematically. METHODS: We propose a new anonymisation method for the release of geographical distances between records of a microdata file-for example patients in a medical database. We discuss a data release scheme in which microdata without coordinates and an additional distance matrix between the corresponding rows of the microdata set are released. In contrast to most other approaches this method preserves small distances better than larger distances. The distances are modified by a variant of Lipschitz embedding. RESULTS: The effects of the embedding parameters on the risk of data disclosure are evaluated by linkage experiments using simulated data. The results indicate small disclosure risks for appropriate embedding parameters. CONCLUSION: The proposed method is useful if published distance information might be misused for the re-identification of records. The method can be used for publishing scientific-use-files and as an additional tool for record-linkage studies