Size segregation of irregular granular materials captured by time-resolved 3D imaging.

When opening a box of mixed nuts, a common experience is to find the largest nuts at the top. This well-known effect is the result of size-segregation where differently sized 'particles' sort themselves into distinct layers when shaken, vibrated or sheared. Colloquially this is known as the 'Brazil-nut effect'. While there have been many studies into the phenomena, difficulties observing granular materials mean that we still know relatively little about the process by which irregular larger particles (the Brazil nuts) reach the top. Here, for the first time, we capture the complex dynamics of Brazil nut motion within a sheared nut mixture through time-lapse X-ray Computed Tomography (CT). We have found that the Brazil nuts do not start to rise until they have first rotated sufficiently towards the vertical axis and then ultimately return to a flat orientation when they reach the surface. We also consider why certain Brazil nuts do not rise through the pack. This study highlights the important role of particle shape and orientation in segregation. Further, this ability to track the motion in 3D will pave the way for new experimental studies of segregating mixtures and will open the door to even more realistic simulations and powerful predictive models. Understanding the effect of size and shape on segregation has implications far beyond food products including various anti-mixing behaviors critical to many industries such as pharmaceuticals and mining.

Well-posed continuum equations for granular flow with compressibility and µ(I)-rheology.

Continuum modelling of granular flow has been plagued with the issue of ill-posed dynamic equations for a long time. Equations for incompressible, two-dimensional flow based on the Coulomb friction law are ill-posed regardless of the deformation, whereas the rate-dependent µ(I)-rheology is ill-posed when the non-dimensional inertial number I is too high or too low. Here, incorporating ideas from critical-state soil mechanics, we derive conditions for well-posedness of partial differential equations that combine compressibility with I-dependent rheology. When the I-dependence comes from a specific friction coefficient µ(I), our results show that, with compressibility, the equations are well-posed for all deformation rates provided that µ(I) satisfies certain minimal, physically natural, inequalities.

Deficient adolescent social behavior following early-life inflammation is ameliorated by augmentation of anandamide signaling.

Early-life inflammation has been shown to exert profound effects on brain development and behavior, including altered emotional behavior, stress responsivity and neurochemical/neuropeptide receptor expression and function. The current study extends this research by examining the impact of inflammation, triggered with the bacterial compound lipopolysaccharide (LPS) on postnatal day (P) 14, on social behavior during adolescence. We investigated the role that the endocannabinoid (eCB) system plays in sociability after early-life LPS. To test this, multiple cohorts of Sprague Dawley rats were injected with LPS on P14. In adolescence, rats were subjected to behavioral testing in a reciprocal social interaction paradigm as well as the open field. We quantified eCB levels in the amygdala of P14 and adolescent animals (anandamide and 2-arachidonoylglycerol) as well as adolescent amygdaloid cannabinoid receptor 1 (CB1) binding site density and the hydrolytic activity of the enzyme fatty acid amide hydrolase (FAAH), which metabolizes the eCB anandamide. Additionally, we examined the impact of FAAH inhibition on alterations in social behavior. Our results indicate that P14 LPS decreases adolescent social behavior (play and social non-play) in males and females at P40. This behavioral alteration is accompanied by decreased CB1 binding, increased anandamide levels and increased FAAH activity. Oral administration of the FAAH inhibitor PF-04457845 (1mg/kg) prior to the social interaction task normalizes LPS-induced alterations in social behavior, while not affecting social behavior in the control group. Infusion of 10ng PF-04457845 into the basolateral amygdala normalized social behavior in LPS injected females. These data suggest that alterations in eCB signaling following postnatal inflammation contribute to impairments in social behavior during adolescence and that inhibition of FAAH could be a novel target for disorders involving social deficits such as social anxiety disorders or autism.

Underlying Asymmetry within Particle Size Segregation.

We experimentally study particle scale dynamics during segregation of a bidisperse mixture under oscillatory shear. Large and small particles show an underlying asymmetry that is dependent on the local particle concentration, with small particles segregating faster in regions of many large particles and large particles segregating slower in regions of many small particles. We quantify the asymmetry on bulk and particle scales, and capture it theoretically. This gives new physical insight into segregation and reveals a similarity with sedimentation, traffic flow, and particle diffusion.

A novel method of continuous cage-side monitoring of hyperthyroid cats treated with radio-iodine.

A continuous monitoring system (MGP DM2000X) was assessed for monitoring γ radiation emissions and determining appropriate isolation times for hyperthyroid cats treated with radioactive iodine (I(131)). Daily radiation emitted by 12 cats who had received a range of doses of I(131) (80-200 MBq) was measured and average background radiation readings deducted. The effective half-lives of the I(131) in the cats were found to have a median of 2.54 days (range 1.40-3.24 days). Cats treated with 200 MBq emitted 5 µGy/day more exposure than cats treated with lower doses throughout the study period (P=0.032). All cats were found to emit a total radiation dose exposure less than 100 µGy (range 0-43 µGy) during days 18-21 of isolation. The potential additional dose exposure to owners was calculated at various days that might be considered for the cats to be returned to their owners. Using this provisional data, maximum isolation periods at this institution could be safely reduced to 17 days as long as certain precautions are followed. This preliminary study demonstrated that this novel cage-side monitoring system can be used to calculate the effective half-life of I(131) and to measure γ radiation exposure from treated cats, which may assist other institutions in determining appropriate isolation times for individual cats.

Fractionation of visuo-spatial memory processes in bipolar depression: a cognitive scaffolding account.

BACKGROUND: Previous studies of neurocognitive performance in bipolar disorder (BD) have demonstrated impairments in visuo-spatial memory. The aim of the present study was to use an object-location memory (OLM) paradigm to assess specific, dissociable processes in visuo-spatial memory and examine their relationship with broader neurocognitive performance. METHOD: Fifty participants (25 patients with BD in a current depressive episode and 25 matched healthy controls) completed the OLM paradigm which assessed three different aspects of visuo-spatial memory: positional memory, object-location binding, and a combined process. Secondary neurocognitive measures of visuo-spatial memory, verbal memory, attention and executive function were also administered. RESULTS: BD patients were significantly impaired on all three OLM processes, with the largest effect in exact positional memory (d = 1.18, p < 0.0001). General deficits were also found across the secondary neurocognitive measures. Using hierarchical regression, verbal learning was found to explain significant variance on the OLM measures where object-identity was present (the object-location binding and combined processes) and accounted for the group difference. The group difference in precise positional memory remained intact. CONCLUSIONS: This study demonstrates that patients with bipolar depression manifest deficits in visuo-spatial memory, with substantial impairment in fine-grain, positional memory. The differential profile of processes underpinning the visuo-spatial memory impairment suggests a form of 'cognitive scaffolding', whereby performance on some measures can be supported by verbal memory. These results have important implications for our understanding of the functional cognitive architecture of mood disorder.

Neurocognitive functioning in bipolar depression: a component structure analysis.

BACKGROUND: Previous studies of neurocognitive performance in bipolar disorder (BD) have focused predominantly on euthymia. In this study we aimed to compare the neurocognitive profile of BD patients when depressed with healthy controls and explore the component structure of neurocognitive processes in these populations. METHOD: Cognitive tests of attention and executive function, immediate memory, verbal and visuospatial learning and memory and psychomotor speed were administered to 53 patients with a SCID-verified diagnosis of BD depression and 47 healthy controls. Test performance was assessed in terms of statistical significance, effect size and percentile standing. Principal component analysis (PCA) was used to explore underlying cognitive factor structure. RESULTS: Multivariate analysis revealed an overall group effect, depressed BD patients performing significantly worse than controls. Patients performed significantly worse on 18/26 measures examined, with large effect sizes (d > 0.8) on tests of speed of processing, verbal learning and specific executive/working memory processes. Almost all tests produced at least one outcome measure on which ∼25-50% of the BD sample performed at more than 1 standard deviation (s.d.) below the control mean. Between 20% and 34% of patients performed at or below the fifth percentile of the control group in working memory, verbal learning and memory, and psychomotor/processing speed. PCA highlighted overall differences between groups, with fewer extracted components and less specificity in patients. CONCLUSIONS: Overall, neurocognitive test performance is significantly reduced in BD patients when depressed. The use of different methods of analysing cognitive performance is highlighted, along with the relationship between processes, indicating important directions for future research.

Adverse life event reporting and worst illness episodes in unipolar and bipolar affective disorders: measuring environmental risk for genetic research.

BACKGROUND: Studies exploring gene-environment interplay in affective disorders now include very large numbers of participants. Methods for evaluating the role of adversity in such studies need to be developed that do not rely on lengthy and labour-intensive interviews. In the present study, a brief questionnaire method for measuring 11 adverse events reported before interview and before their worst illness episodes by bipolar, unipolar and healthy control participants, participating in genetic association studies, was evaluated. METHOD: Five hundred and twelve bipolar disorder (BD) participants, 1447 participants with recurrent unipolar depression (UPD) and 1346 psychiatrically healthy control participants underwent the researcher-administered version of the List of Threatening Experiences Questionnaire (LTE-Q) for the 6 months before their worst affective episodes for UPD and BD participants, and for the 6 months before interview for the UPD participants and controls. RESULTS: UPD and BD cases were significantly more likely to report at least one event, as well as more events in the 6 months before interview and before their worst illness episodes, than healthy controls. Both manic and depressive episodes were significantly associated with adverse events in the BD cases. Depressed mood at the time of interview influenced event reporting in UPD and control participants but not the BD cases. Age was negatively correlated with the number of events reported by controls. CONCLUSIONS: The researcher-administered LTE-Q provides a measure of case-control differences for adversity that is applicable in large genetic association studies. Confounding factors for event reporting include present mood and age.

Incidence and correlates of radiation dermatitis in children and adolescents receiving radiation therapy for the treatment of paediatric sarcomas.

AIMS: To investigate the relationship between the maximum grade of skin toxicity, radiation dose and clinical variables in children receiving treatment for sarcomas involving the bone and soft tissue. MATERIALS AND METHODS: Between January 2003 and July 2006, 82 patients with musculoskeletal tumours on an Institutional Review Board (IRB)-approved prospective study at St. Jude Children's Research Hospital received three-dimensional conformal or intensity-modulated radiation therapy for local tumour control. Radiation dermatitis was graded according to the National Cancer Institute's Common Toxicity Criteria version 2.0 during and after radiation therapy. The dose to the skin was calculated for each patient from the radiation treatment plan. RESULTS: The radiation doses delivered to the primary tumour ranged from 4140 to 7020cGy, with a mean dose of 5040cGy. The maximum recorded grade of skin toxicity was: grade 0: seven patients (8.6%); grade 1: 26 patients (31.7%); grade 2: 37 patients (45.1%); grade 3: 10 patients (12.2%); grade 4: two patients (2.4%). A significant association for increased grade of skin toxicity was observed between dose (P<0.01), volume of skin treated above 4000cGy (P=0.03), use of a bolus (P<0.01), Caucasian race (P<0.01) and related pain (P<0.01). CONCLUSIONS: These findings suggest that the delivered dose, use of a bolus, the volume treated, and race may be used in the clinical setting to predict patients at risk for skin toxicity. Alterations in treatment technique and early therapeutic intervention may help to reduce or eliminate radiation-induced skin side-effects and associated pain.

The changing natural history of spinal muscular atrophy type 1.

BACKGROUND: Noninvasive ventilation has become increasingly available to spinal muscular atrophy (SMA) patients since the early 1990 s. This is expected to have improved survival for SMA type 1 patients. OBJECTIVE: To assess whether there has been a change in survival in patients with SMA type 1 between 1980 and 2006. METHODS: We used deidentified, family-reported data from participants in the International Spinal Muscular Atrophy Patient Registry and obtained additional clinical information through a mail-in questionnaire. One hundred forty-three patients with SMA type 1 were included in the analysis. Survival of patients born in 1995-2006 (n = 78) was compared with that of patients born in 1980-1994 (n = 65), using the Kaplan-Meier method and Cox proportional hazards models with age at death as the outcome. RESULTS: Patients born in 1995 though 2006 had significantly increased survival compared with those born in 1980-1994 (log-rank test, p < 0.001). In a Cox model, patients born in 1995-2006 had a 70% reduction in the risk of death compared with those born in 1980-1994 (hazard ratio [HR] 0.3, 95% CI 0.2-0.5, p < 0.001) over a mean follow-up of 49.9 months (SD 61.1, median 22.0). However, when controlling for demographic and clinical care variables, year of birth was no longer significantly associated with age at death (HR 1.0, 95% CI 0.6-1.8, p = 0.9), whereas ventilation for more than 16 h/d, use of a mechanical insufflation-exsufflation device, and gastrostomy tube feeding showed a significant effect in reducing the risk of death. CONCLUSION: Survival in spinal muscular atrophy type 1 patients has increased in recent years, in relation to the growing trend toward more proactive clinical care.

Occurrence of proteolytic activity and N-acyl-homoserine lactone signals in the spoilage of aerobically chill-stored proteinaceous raw foods.

Proteolytic pseudomonads dominate the spoilage flora of aerobically chill-stored proteinaceous raw foods. Proteolysis during spoilage of these food systems affects both food quality and the dynamics of the bacterial community because it increases the availability of nutrients to the community as a whole. Quorum sensing, or cell-cell signaling, is associated closely with ecological interactions among bacteria in mixed communities. The potential role of quorum sensing in proteolytic food spoilage was examined, based on the evaluation of N-acyl-homoserine lactone (AHL) signal molecules. The occurrence of proteolytic activity and AHL signals was studied during spoilage of aerobically chill-stored ground beef, fish, chicken, and raw milk. Pseudomonads dominated the psychrotrophic flora, followed distantly by members of the Enterobacteriaceae. The growth of pseudomonads was correlated with the occurrence of proteolytic activity in all food systems. AHL concentration began increasing significantly only after the onset of proteolytic activity. Widely divergent AHL profiles were revealed by thin-layer chromatography analysis of the different food samples, and these profiles were likely determined by the undefined bacterial flora in these systems and by the characterized pseudomonads and Enterobacteriaceae. Although Hafnia alvei was a major component of the Enterobacteriaceae flora in all foods tested and a strong AHL producer, the signal molecules produced by H. alvei strain EB1 did not influence protease production by Pseudomonas fluorescens strain 395 in vitro. These results do not indicate any clear correlation between the overall detectable AHL signal molecules accumulated in the food samples and proteolytic activity.

Pattern selection by a granular wave in a rotating drum.

The results of an experimental investigation of granular segregation in a thin rotating drum are presented. A mechanism based on the presence of an uphill wave of particles has been found to govern the observed pattern of petals. Specifically we develop a simple model that captures the essential physics of the segregation and yields an algebraic expression that predicts the number of petals in the pattern.

The distribution of cement penetration into bovine acetabular bone utilising various pressurisation techniques.

Most mechanical failures of acetabular fixation within ten years of primary cemented hip replacement are attributable to a failure to achieve good initial fixation of bone and cement. Several studies have suggested that to achieve good fixation between bone and cement between 3 mm and 5 mm of cement penetration into bone is desirable. Whilst several acetabular cement pressurisation systems exist, little is known about the effects of cement pressurisation on the pattern of penetration of cement into cancellous bone within the pelvis. The current paper assesses the penetration of bone cement into bovine acetabular bone by various pressurisation techniques. We found that pressurisation with the use of a swab in glove or the DePuy pressuriser led to improvement in cement penetration both in terms of maximum depth and also percentage cover of the cup by cement (p<0.05). There was no significant difference in mean maximal penetration between the use of the pressuriser and the swab in a glove technique (p=0.3). If only a plain cup was used as a pressuriser, the penetration achieved was significantly lower in comparison to use of a pressuriser (p<0.02). When compared to previously documented acrylic models, the pattern of intrusion noted in the bovine model was different: penetration was lower at the equatorial and base regions of the acetabulum.

Management of the giant-cell tumours of the distal radius.

BACKGROUND: Giant-cell tumour of the distal radius is a rare neoplasm that affects the peri-articular metaphysial region of the bone. Curettage alone or with bone grafting has been reported to be associated with high incidence of local recurrence in these tumours. In the present series, we report the results of curettage only as the treatment for primary giant-cell tumour of the distal radius carried out at a single centre. PATIENTS AND RESULTS: A total of 287 patients with giant-cell tumour have been referred to us for treatment over the last 28 years; 24 of these were found to have lesion in the distal radius. One patient underwent endoprosthetic replacement of the distal radius. The remaining 23 patients underwent curettage of the primary neoplasm. Four out of the 23 (17%) patients developed local recurrence of disease, The mean time to local recurrence was 17 months (range, 9-27 months). Complications such as collapse of the articular cartilage are more common in patients with an extensive soft tissue component of the tumour. CONCLUSIONS: Curettage alone is adequate treatment for the majority of patients with giant-cell tumours of the distal radius but some form of stabilisation may be required in the presence of extensive bone destruction.

Peroneal tenosynovitis following ankle sprains.

Peroneal tenosynovitis has a variety of causes which include inversion injury of the ankle. It is rarely reported and frequently misdiagnosed. We report the operative findings and outcome of surgical decompression in 19 patients who clinically presented following inversion injury with features suggestive of peroneal tenosynovitis. A review of the literature of this pathology is presented.

Cognitive deficit induced by acute tryptophan depletion in patients with Alzheimer's disease.

OBJECTIVE: The study assessed the effects on global cognitive function and mood of a reduction of brain serotonin by means of acute tryptophan depletion in 16 patients with dementia of the Alzheimer type and in 16 cognitively intact comparison subjects. METHOD: In a double-blind, crossover design, subjects received a tryptophan-free amino acid drink to induce acute tryptophan depletion and, on a separate occasion, a placebo drink containing a balanced mixture of amino acids. On each occasion, ratings of depressed mood were made at baseline and 4 and 7 hours later, and the Modified Mini-Mental State was administered at baseline and 4 hours later. RESULTS: Patients with dementia of the Alzheimer type had a significantly lower mean score on the Modified Mini-Mental State after acute tryptophan depletion than after receiving placebo. The comparison group showed no difference in mean score on the Modified Mini-Mental State after acute tryptophan depletion and after receiving placebo. No significant changes in mood were found in either group. CONCLUSIONS: Acute tryptophan depletion significantly impaired cognitive function in patients with dementia of the Alzheimer type. Compromised serotonergic function, in combination with cholinergic deficit, may make an important contribution to cognitive decline in dementia of the Alzheimer type.

The standardized family: an innovation in primary care education at the University of Massachusetts.

In 1995 as part of The Robert Wood Johnson Foundation's Generalist Physician Initiative, the University of Massachusetts (UMass) Medical School developed the "standardized family" as a new model for teaching the essential elements of primary care in a core curriculum format outside of the clinical setting. Using this model, a hypothetical family unit (the "McQ Family") serves as the focus for case-based clinical problem solving. This paper describes the standardized family model and provides two years of evaluation outcomes such as curriculum assessments, student performance outcomes, and correlation with external measures of clinical performance to support the effectiveness of this educational model. It discusses the transferability of the standardized family model from UMass Medical School to Pennsylvania State University College of Medicine and uses Pennsylvania State's adaptation (the "Hershey-Penn Family") to illustrate how the standardized family can be customized to integrate a core curriculum into a three-year longitudinal primary care program. The authors suggest that the standardized family model has the potential to meet a broad range of primary care teaching needs at other institutions.