Apparatus for histological validation of in vivo and ex vivo magnetic resonance imaging of the human prostate

This article describes apparatus to aid histological validation of magnetic resonance imaging studies of the human prostate. The apparatus includes a 3D-printed patientspecific mold that facilitates aligned in vivo and ex vivo imaging, in situ tissue fixation, and tissue sectioning with minimal organ deformation. The mold and a dedicated container include MRI-visible landmarks to enable consistent tissue positioning and minimize image registration complexity. The inclusion of high spatial resolution ex vivo imaging aids in registration of in vivo MRI and histopathology data

Integration across time determines path deviation discrimination for moving objects.

YesBackground: Human vision is vital in determining our interaction with the outside world. In this study we characterize our ability to judge changes in the direction of motion of objects-a common task which can allow us either to intercept moving objects, or else avoid them if they pose a threat. Methodology/Principal Findings: Observers were presented with objects which moved across a computer monitor on a linear path until the midline, at which point they changed their direction of motion, and observers were required to judge the direction of change. In keeping with the variety of objects we encounter in the real world, we varied characteristics of the moving stimuli such as velocity, extent of motion path and the object size. Furthermore, we compared performance for moving objects with the ability of observers to detect a deviation in a line which formed the static trace of the motion path, since it has been suggested that a form of static memory trace may form the basis for these types of judgment. The static line judgments were well described by a 'scale invariant' model in which any two stimuli which possess the same two-dimensional geometry (length/width) result in the same level of performance. Performance for the moving objects was entirely different. Irrespective of the path length, object size or velocity of motion, path deviation thresholds depended simply upon the duration of the motion path in seconds. Conclusions/Significance: Human vision has long been known to integrate information across space in order to solve spatial tasks such as judgment of orientation or position. Here we demonstrate an intriguing mechanism which integrates direction information across time in order to optimize the judgment of path deviation for moving objects.Wellcome Trust, Leverhulme Trust, NI

Genetic relationships and evolution in Cucurbita pepo (pumpkin, squash, gourd) as revealed by simple sequence repeat polymorphisms

Genetic relationships among 104 accessions of Cucurbita pepo were assessed from polymorphisms in 134 SSR (microsatellite) and four SCAR loci, yielding a total of 418 alleles, distributed among all 20 linkage groups. Genetic distance values were calculated, a dendrogram constructed, and principal coordinate analyses conducted. The results showed 100 of the accessions as distributed among three clusters representing each of the recognized subspecies, pepo, texana, and fraterna. The remaining four accessions, all having very small, round, striped fruits, assumed central positions between the two cultivated subspecies, pepo and texana, suggesting that they are relicts of undescribed wild ancestors of the two domesticated subspecies. In both, subsp. texana and subsp. pepo, accessions belonging to the same cultivar-group (fruit shape) associated with one another. Within subsp. pepo, accessions grown for their seeds or that are generalists, used for both seed and fruit consumption, assumed central positions. Specialized accessions, grown exclusively for consumption of their young fruits, or their mature fruit flesh, or seed oil extraction, tended to assume outlying positions, and the different specializations radiated outward from the center in different directions. Accessions of the longest-fruited cultivar-group, Cocozelle, radiated bidirectionally, indicating independent selection events for long fruits in subsp. pepo probably driven by a common desire to consume the young fruits. Among the accessions tested, there was no evidence for crossing between subspecies after domestication

Obesity prevalence estimates in a Canadian regional population of preschool children using variant growth references

<p>Abstract</p> <p>Background</p> <p>Childhood obesity is a public health problem in Canada. Accurate measurement of a health problem is crucial in defining its burden. The objective of this study is to compare the prevalence estimates of overweight and obesity in preschool children using three growth references.</p> <p>Methods</p> <p>Weights and heights were measured on 1026 preschool children born in Newfoundland and Labrador (NL), Canada, and body mass index calculated. The prevalence of overweight and obesity was determined and statistical comparisons conducted among the three growth references; the Centres for Disease Control (CDC), the International Obesity Task Force (IOTF) and the World Health Organization (WHO).</p> <p>Results</p> <p>CDC and IOTF produced similar estimates of the prevalence of overweight, 19.1% versus 18.2% while the WHO reported a higher prevalence 26.7% (p < .001). The CDC classified twice as many children as obese compared to the IOTF 16.6% versus 8.3% (p < .001) and a third more than the WHO 16.6% versus 11.3% (p < .01). There was variable level of agreement between methods.</p> <p>Conclusions</p> <p>The CDC reported a much higher prevalence of obesity compared to the other references. The prevalence of childhood obesity is dependent on the growth reference used.</p

The Effect of Viewing Eccentricity on Enumeration

Visual acuity and contrast sensitivity progressively diminish with increasing viewing eccentricity. Here we evaluated how visual enumeration is affected by visual eccentricity, and whether subitizing capacity, the accurate enumeration of a small number (∼3) of items, decreases with more eccentric viewing. Participants enumerated gratings whose (1) stimulus size was constant across eccentricity, and (2) whose stimulus size scaled by a cortical magnification factor across eccentricity. While we found that enumeration accuracy and precision decreased with increasing eccentricity, cortical magnification scaling of size neutralized the deleterious effects of increasing eccentricity. We found that size scaling did not affect subitizing capacities, which were nearly constant across all eccentricities. We also found that size scaling modulated the variation coefficients, a normalized metric of enumeration precision, defined as the standard deviation divided by the mean response. Our results show that the inaccuracy and imprecision associated with increasing viewing eccentricity is due to limitations in spatial resolution. Moreover, our results also support the notion that the precise number system is restricted to small numerosities (represented by the subitizing limit), while the approximate number system extends across both small and large numerosities (indexed by variation coefficients) at large eccentricities

Clinical experience with the Bicarbon heart valve prosthesis

BACGROUND: We have previously reported mid-term results of a study, which ended in January 2000, on the Bicarbon valve. The study concluded that the valve showed excellent clinical results, associated with a low incidence of valve-related complications. In the present study, the same patients were prospectively followed for an additional 5 years. METHODS: Forty-four patients had aortic valve replacement (AVR), 48 had mitral valve replacement (MVR), and 13 had both aortic and mitral valve replacement (DVR). The mean age of the 105 patients was 61.2 ± 11.3 years. The mean follow-up was 6.1 ± 1.9 years with a cumulative follow-up of 616 patient-years. RESULTS: There were 5 early deaths (4.7%: 4 in the AVR group and 1 in the MVR group) and 21 late deaths (3.4%/patient-year: 5 valve related deaths and 16 valve unrelated deaths). Survival at 8 years was 75.2 ± 7.0% in the AVR group, 76.6 ± 6.2% in the MVR group, and 55.4 ± 16.1% in the DVR group. The linearized incidence of thrombo-embolic complications, hemorrhagic complications, and paravalvular leaks in all patients was 0.65 ± 1.48%, 0.81 ± 1.69%, and 0.16 ± 0.54%/patient-year respectively. No other complications were observed. CONCLUSION: The Bicarbon prosthetic heart valve has shown excellent long-term clinical results, associated with a low incidence of valve-related complications

Hereditary sensory neuropathy type I

Hereditary sensory neuropathy type I (HSN I) is a slowly progressive neurological disorder characterised by prominent predominantly distal sensory loss, autonomic disturbances, autosomal dominant inheritance, and juvenile or adulthood disease onset. The exact prevalence is unknown, but is estimated as very low. Disease onset varies between the 2nd and 5th decade of life. The main clinical feature of HSN I is the reduction of sensation sense mainly distributed to the distal parts of the upper and lower limbs. Variable distal muscle weakness and wasting, and chronic skin ulcers are characteristic. Autonomic features (usually sweating disturbances) are invariably observed. Serious and common complications are spontaneous fractures, osteomyelitis and necrosis, as well as neuropathic arthropathy which may even necessitate amputations. Some patients suffer from severe pain attacks. Hypacusis or deafness, or cough and gastrooesophageal reflux have been observed in rare cases. HSN I is a genetically heterogenous condition with three loci and mutations in two genes (SPTLC1 and RAB7) identified so far. Diagnosis is based on the clinical observation and is supported by a family history. Nerve conduction studies confirm a sensory and motor neuropathy predominantly affecting the lower limbs. Radiological studies, including magnetic resonance imaging, are useful when bone infections or necrosis are suspected. Definitive diagnosis is based on the detection of mutations by direct sequencing of the SPTLC1 and RAB7 genes. Correct clinical assessment and genetic confirmation of the diagnosis are important for appropriate genetic counselling and prognosis. Differential diagnosis includes the other hereditary sensory and autonomic neuropathies (HSAN), especially HSAN II, as well as diabetic foot syndrome, alcoholic neuropathy, neuropathies caused by other neurotoxins/drugs, immune mediated neuropathy, amyloidosis, spinal cord diseases, tabes dorsalis, lepra neuropathy, or decaying skin tumours like amelanotic melanoma. Management of HSN I follows the guidelines given for diabetic foot care (removal of pressure to the ulcer and eradication of infection, followed by the use of specific protective footwear) and starts with early and accurate counselling of patients about risk factors for developing foot ulcerations. The disorder is slowly progressive and does not influence life expectancy but is often severely disabling after a long duration of the disease

Evaluation of PSA and PSA Density in a Multiparametric Magnetic Resonance Imaging-Directed Diagnostic Pathway for Suspected Prostate Cancer: The INNOVATE Trial

OBJECTIVES: To assess the clinical outcomes of mpMRI before biopsy and evaluate the space remaining for novel biomarkers. METHODS: The INNOVATE study was set up to evaluate the validity of novel fluidic biomarkers in men with suspected prostate cancer who undergo pre-biopsy mpMRI. We report the characteristics of this clinical cohort, the distribution of clinical serum biomarkers, PSA and PSA density (PSAD), and compare the mpMRI Likert scoring system to the Prostate Imaging–Reporting and Data System v2.1 (PI-RADS) in men undergoing biopsy. RESULTS: 340 men underwent mpMRI to evaluate suspected prostate cancer. 193/340 (57%) men had subsequent MRI-targeted prostate biopsy. Clinically significant prostate cancer (csigPCa), i.e., overall Gleason ≥ 3 + 4 of any length OR maximum cancer core length (MCCL) ≥4 mm of any grade including any 3 + 3, was found in 96/195 (49%) of biopsied patients. Median PSA (and PSAD) was 4.7 (0.20), 8.0 (0.17), and 9.7 (0.31) ng/mL (ng/mL/mL) in mpMRI scored Likert 3,4,5 respectively for men with csigPCa on biopsy. The space for novel biomarkers was shown to be within the group of men with mpMRI scored Likert3 (178/340) and 4 (70/350), in whom an additional of 40% (70/178) men with mpMRI-scored Likert3, and 37% (26/70) Likert4 could have been spared biopsy. PSAD is already considered clinically in this cohort to risk stratify patients for biopsy, despite this 67% (55/82) of men with mpMRI-scored Likert3, and 55% (36/65) Likert4, who underwent prostate biopsy had a PSAD below a clinical threshold of 0.15 (or 0.12 for men aged <50 years). Different thresholds of PSA and PSAD were assessed in mpMRI-scored Likert4 to predict csigPCa on biopsy, to achieve false negative levels of ≤5% the proportion of patients whom who test as above the threshold were unsuitably high at 86 and 92% of patients for PSAD and PSA respectively. When PSA was re tested in a sub cohort of men repeated PSAD showed its poor reproducibility with 43% (41/95) of patients being reclassified. After PI-RADS rescoring of the biopsied lesions, 66% (54/82) of the Likert3 lesions received a different PI-RADS score. CONCLUSIONS: The addition of simple biochemical and radiological markers (Likert and PSAD) facilitate the streamlining of the mpMRI-diagnostic pathway for suspected prostate cancer but there remains scope for improvement, in the introduction of novel biomarkers for risk assessment in Likert3 and 4 patients, future application of novel biomarkers tested in a Likert cohort would also require re-optimization around Likert3/PI-RADS2, as well as reproducibility testing

Aging and Visual Counting

Much previous work on how normal aging affects visual enumeration has been focused on the response time required to enumerate, with unlimited stimulus duration. There is a fundamental question, not yet addressed, of how many visual items the aging visual system can enumerate in a "single glance", without the confounding influence of eye movements.We recruited 104 observers with normal vision across the age span (age 21-85). They were briefly (200 ms) presented with a number of well- separated black dots against a gray background on a monitor screen, and were asked to judge the number of dots. By limiting the stimulus presentation time, we can determine the maximum number of visual items an observer can correctly enumerate at a criterion level of performance (counting threshold, defined as the number of visual items at which ≈63% correct rate on a psychometric curve), without confounding by eye movements. Our findings reveal a 30% decrease in the mean counting threshold of the oldest group (age 61-85: ∼5 dots) when compared with the youngest groups (age 21-40: 7 dots). Surprisingly, despite decreased counting threshold, on average counting accuracy function (defined as the mean number of dots reported for each number tested) is largely unaffected by age, reflecting that the threshold loss can be primarily attributed to increased random errors. We further expanded this interesting finding to show that both young and old adults tend to over-count small numbers, but older observers over-count more.Here we show that age reduces the ability to correctly enumerate in a glance, but the accuracy (veridicality), on average, remains unchanged with advancing age. Control experiments indicate that the degraded performance cannot be explained by optical, retinal or other perceptual factors, but is cortical in origin