Competing Timescales Lead to Oscillations in Shear-Thickening Suspensions.

Competing timescales generate novelty. Here, we show that a coupling between the timescales imposed by instrument inertia and the formation of interparticle frictional contacts in shear-thickening suspensions leads to highly asymmetric shear-rate oscillations. Experiments tuning the presence of oscillations by varying the two timescales support our model. The observed oscillations give access to a shear-jamming portion of the flow curve that is forbidden in conventional rheometry. Moreover, the oscillation frequency allows us to quantify an intrinsic relaxation time for particle contacts. The coupling of fast contact network dynamics to a slower system variable should be generic to many other areas of dense suspension flow, with instrument inertia providing a paradigmatic example.

Constraint-Based Approach to Granular Dispersion Rheology.

We present a phenomenological model for granular suspension rheology in which particle interactions enter as constraints to relative particle motion. By considering constraints that are formed and released by stress respectively, we derive a range of experimental flow curves in a single treatment and predict singularities in viscosity and yield stress consistent with literature data. Fundamentally, we offer a generic description of suspension flow that is independent of bespoke microphysics.

Automated vocal analysis of naturalistic recordings from children with autism, language delay, and typical development.

For generations the study of vocal development and its role in language has been conducted laboriously, with human transcribers and analysts coding and taking measurements from small recorded samples. Our research illustrates a method to obtain measures of early speech development through automated analysis of massive quantities of day-long audio recordings collected naturalistically in children's homes. A primary goal is to provide insights into the development of infant control over infrastructural characteristics of speech through large-scale statistical analysis of strategically selected acoustic parameters. In pursuit of this goal we have discovered that the first automated approach we implemented is not only able to track children's development on acoustic parameters known to play key roles in speech, but also is able to differentiate vocalizations from typically developing children and children with autism or language delay. The method is totally automated, with no human intervention, allowing efficient sampling and analysis at unprecedented scales. The work shows the potential to fundamentally enhance research in vocal development and to add a fully objective measure to the battery used to detect speech-related disorders in early childhood. Thus, automated analysis should soon be able to contribute to screening and diagnosis procedures for early disorders, and more generally, the findings suggest fundamental methods for the study of language in natural environments.

Plain radiographs for the assessment of coronectomy: not always a case of black or white.

In recent years, coronectomy of impacted lower third molar teeth has become an increasingly popular alternative to removal. Traditionally, orthopantomograms of mandibular third molars have been used to indicate features that show that the tooth is in close proximity to, or in an intimate relation with, the inferior dental nerve. Some authors advocate coronectomy as opposed to surgical removal to reduce the risk of damage to the nerve. In our Trust during the last two years, there has been a noticeable increase in the prescription of coronectomy for the management of pericoronitis associated with mandibular third molars. The purpose of this study therefore was to examine the differences among clinicians in their assessment of the need for coronectomy using plain-view radiographs. An online survey was completed by 25 clinicians with different levels of experience from six units across the UK and Republic of Ireland. We found a wide variation in the number of coronectomies prescribed (intraclass correlation 2.67), and when prescribed, a lack of agreement about the radiographic feature that had influenced the decision. These judgments are not straightforward. They are, to some extent, subjective, and in certain cases may benefit from a team-led approach.

SMAD4 mutations found in unselected HHT patients.

BACKGROUND: Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disease exhibiting multifocal vascular telangiectases and arteriovenous malformations. The majority of cases are caused by mutations in either the endoglin (ENG) or activin receptor-like kinase 1 (ALK1, ACVRL1) genes; both members of the transforming growth factor (TGF)-beta pathway. Mutations in SMAD4, another TGF-beta pathway member, are seen in patients with the combined syndrome of juvenile polyposis (JP) and HHT (JP-HHT). METHODS: We sought to determine if HHT patients without any apparent history of JP, who were undergoing routine diagnostic testing, would have mutations in SMAD4. We tested 30 unrelated HHT patients, all of whom had been referred for DNA based testing for HHT and were found to be negative for mutations in ENG and ALK1. RESULTS: Three of these people harboured mutations in SMAD4, a rate of 10% (3/30). The SMAD4 mutations were similar to those found in other patients with the JP-HHT syndrome. CONCLUSIONS: The identification of SMAD4 mutations in HHT patients without prior diagnosis of JP has significant and immediate clinical implications, as these people are likely to be at risk of having JP-HHT with the associated increased risk of gastrointestinal cancer. We propose that routine DNA based testing for HHT should include SMAD4 for samples in which mutations in neither ENG nor ALK1 are identified. HHT patients with SMAD4 mutations should be screened for colonic and gastric polyps associated with JP.

Family-focused treatment of bipolar disorder: 1-year effects of a psychoeducational program in conjunction with pharmacotherapy.

BACKGROUND: Few studies have examined the combined effects of psychosocial treatment and pharmacotherapy for bipolar disorder. This study used a randomized, controlled design to examine a 9-month, manual-based program of family-focused psychoeducational treatment (FFT). METHODS: Bipolar patients (N = 101) were recruited shortly after an illness episode and randomly assigned to 21 sessions of FFT (n = 31) or to a comparison treatment involving two family education sessions and follow-up crisis management (CM; n = 70). Both treatments were delivered over 9 months; patients were simultaneously maintained on mood stabilizing medications. Patients were evaluated every 3 months for 1 year as to relapse status, symptom severity, and medication compliance. RESULTS: Patients assigned to FFT had fewer relapses and longer delays before relapses during the study year than did patients in CM. Patients in FFT also showed greater improvements in depressive (but not manic) symptoms. The most dramatic improvements were among FFT patients whose families were high in expressed emotion. The efficacy of FFT could not be explained by differences among patients in medication regimes or compliance. CONCLUSIONS: Family-focused psychoeducational treatment appears to be an efficacious adjunct to pharmacotherapy for bipolar disorder. Future studies should evaluate family treatment against other forms of psychotherapy matched in amount of therapist-patient contact.

Kinetic evaluation of carrier-mediated transport of ouabain and taurocholic acid in isolated rat hepatocytes. Evidence for independent transport systems.

Ouabain and taurocholic acid (Tch) share in common the cyclopentanophenanthrene (steroid) nucleus, and both are concentrated in the liver by hepatic sinusoidal carrier-mediated transport processes. Multiple transport systems for Tch uptake have been implicated, and Tch is an effective inhibitor of ouabain uptake. To determine if the ouabain transport system is related to transport of Tch, kinetic studies were conducted to examine the nature of cross-inhibition of ouabain and Tch. Tch was found to inhibit ouabain uptake in a competitive manner, with a Ki approximately ten times less than the Km for ouabain. However, ouabain failed to inhibit total Tch uptake in a competitive manner when added to the system at the same time as the Tch substrate. Preincubation of cells with ouabain resulted in noncompetitive inhibition of sodium-dependent Tch uptake but had no effect on sodium-independent Tch uptake. Ouabain had a weak competitive inhibitory effect on sodium-independent transport of Tch, but the Ki was approximately ten times greater than the Km for ouabain. These results demonstrate that the ouabain transport system is distinct from both the sodium-dependent and sodium-independent transport systems for Tch. Tch apparently binds competitively to the ouabain transport system but is not effectively transported across the cell membrane by this system.

Diagnostic and therapeutic dilemmas in the management of pediatric-onset bipolar disorder.

Although the diagnosis of pediatric-onset bipolar disorder is controversial, an increasing literature of systematic research has challenged the traditional view that this disorder is a rare condition. This article summarizes research regarding the atypical presentation of pediatric bipolar disorder and its overlap with attention-deficit/hyperactivity disorder and other comorbid conditions, as well as family-genetic and treatment data. When structured interview data were examined, cases of pediatric mania constituted 16% of referrals to our outpatient clinic. Presentation is atypical by adult standards and includes irritability, chronicity, and mixed state. Family-genetic and treatment data help to establish diagnostic validity. Pediatric bipolar disorder is not a rare condition. Treatment requires a combined pharmacotherapy approach to address issues of comorbidity. Atypical antipsychotic medications have provided promising treatment results, but additional controlled clinical trials are needed.

Molecular pharmacology of aromatase and its regulation by endogenous and exogenous agents.

Aromatase (estrogen synthase) is the cytochrome P450 enzyme complex that converts C19 androgens to C18 estrogens. Aromatase activity has been demonstrated in breast tissue in vitro, and expression of aromatase is highest in or near breast tumor sites. Thus, local regulation of aromatase by both endogenous factors as well as exogenous medicinal agents will influence the levels of estrogen available for breast cancer growth. The prostaglandin E2 (PGE2) increases intracellular cAMP levels and stimulates estrogen biosynthesis, and our recent studies have shown a strong linear association between CYP19 expression and the sum of COX-1 and COX-2 expression in breast cancer specimens. PGE2 can bind to four receptor subtypes, EP1-EP4, which are coupled to different intracellular signaling pathways. In primary human breast stromal cell cultures, aromatase activity was significantly induced by PGE2, dexamethasone, and agonists for the EP1 and EP2 receptor subtypes. An EP1 antagonist, SC-19220, inhibited the induction of enzyme activity by PGE2 or 17-phenyltrinor-PGE2, an EP1 agonist. Sulprostone, an EP3 agonist, did not alter aromatase activity levels. Investigations are also underway on the regulation of aromatase by exogenous medicinal agents. Selective steroidal and nonsteroidal agents are effective in inhibiting breast tissue aromatase. The benzopyranone ring system is a molecular scaffold of considerable interest, and this scaffold is found in certain flavonoid natural products that have weak aromatase inhibitory activity. Our novel synthetic route for benzopyranones utilizes readily available salicylic acids and terminal alkynes as starting materials. The synthesis of flavones with diversity on the benzopyranone moiety and at the C-2 position occurs with good to excellent yields using these reaction conditions, resulting in an initial benzopyranone library of thirty compounds exhibiting enhanced and differential aromatase inhibition. Current medicinal chemistry efforts focus on diversifying the benzopyranone scaffold and utilizing combinatorial chemistry approaches to construct small benzopyranone libraries as potential aromatase inhibitors.

Expressed emotion and attributions in the relatives of bipolar patients: an analysis of problem-solving interactions.

Among the relatives of schizophrenic and depressed patients, high expressed emotion (EE) attitudes are associated with "controllability attributions" about the causes of patients' symptoms and problem behaviors. However, previous studies have judged EE attitudes and causal attributions from the same assessment measure, the Camberwell Family Interview (CFI; C. E. Vaughn & J. P. Leff, 1976). The authors examined causal attributions among relatives of 47 bipolar patients, as spontaneously expressed to patients in family problem-solving interactions during a postillness period. Relatives rated high EE during the patients' acute episode (based on the CFI) were more likely than relatives rated low EE to spontaneously attribute patients' symptoms and negative behaviors to personal and controllable factors during the postillness interactional assessment. Thus, the EE-attribution linkage extends to the relatives of bipolar patients evaluated during a family interaction task.

Bipolar disorder and family communication: effects of a psychoeducational treatment program.

Family psychoeducational programs are efficacious adjuncts to pharmacotherapy for patients with schizophrenic and bipolar disorders, but little is known about what these programs change about families. The authors assessed changes in face-to-face interactional behavior over 1 year among families of bipolar patients who received a 9-month family-focused psychoeducational therapy (FFT; n = 22) or crisis management with naturalistic follow-up (CMNF; n = 22), both administered with maintenance pharmacotherapy. Members of families who received FFT showed more positive nonverbal interactional behavior during a 1-year posttreatment problem-solving assessment than families who received CMNF, although no corresponding decreases were seen in negative interactional behaviors. The positive effect of family treatment on patients' symptom trajectories over 1 year was partially mediated by increases in patients' positive nonverbal interactional behaviors during this same interval.

Effect of a single bolus of intracoronary basic fibroblast growth factor on perfusion in an ischemic porcine model.

Basic fibroblast growth factor (bFGF) has been shown to induce angiogenesis in various animal models, but the methods of administration used experimentally are not clinically feasible. The objective of this study was to determine whether a single intracoronary bolus injection of bFGF would improve coronary perfusion in a porcine ischemic model that mimics clinical chronic ischemia. A copper coil studded with gold was delivered into the proximal right coronary artery of juvenile Yorkshire pigs and deployed by interventional techniques. After a four-week interval for stenosis maturation, bFGF (100 micrograms) was administered by bolus injection into the left coronary artery in five animals, and vehicle alone was administered in four animals. Angiogenesis and change in right coronary perfusion area were assessed two weeks later by angiography, myocardial contrast echocardiography and immunohistochemistry. The right coronary perfusion area increased significantly after treatment in all but one of the animals that received bFGF but not in any of the controls. Intimal hyperplasia was not induced by bFGF. Capillary density determined histochemically was not different in the two groups. In conclusion, in a porcine ischemic model, bFGF administered by a single bolus intracoronary injection into the contralateral artery improved antegrade perfusion into the ischemic territory although without histological evidence of angiogenesis. This preliminary work merits further investigation.

Pixel labeling by supervised probabilistic relaxation.

A simple modification to existing probabilistic relaxation procedures is suggested which allows the information contained in initial labels to exert an influence on the direction of relaxation throughout the process. In this manner, the initial labels assume more importance than with conventional algorithms and are used in combination with the outcome of relaxation at each iteration to produce a cooperative estimate of the correct label for a particular object. Pixel labeling examples are presented which show the performance that can be obtained with the modified algorithm. The procedure is readily generalized to allow other data to influence the process.

High performance liquid chromatography assay for piroxicam in pharmaceutical products.

A high performance liquid chromatographic assay for piroxicam in pharmaceutical preparations is described. The method uses a reversed-phase C18 column with pH 3 aqueous buffer/methanol, 55:45, v/v mobile phase, and is selective for piroxicam in the presence of other "oxicams," synthetic precursors, by-products, degradation products, metabolites, and related compounds. Applications to capsules, tablets, ointments, suppositories, ophthalmic suspensions, and rodent feeds are cited.

Battering in a population of adolescent females.

The purpose of this study was to assess the prevalence of battering in a population of adolescent females, to gain information regarding the impact of battering on their health, and to test a portion of the Campbell and Humphreys (1984) framework, which states that our patriarchal society and the resulting machismo attitudes toward women are the cause of battering. If the framework is correct, partners who batter would possess characteristics indicative of machismo. The sample for this descriptive study consisted of a convenience sample of 59 females from a shelter for displaced teens. The subjects provided information on themselves and 92 male partners via interviews. Of 59 subjects, 69% had been battered before the age of 18 and 41.5% had been battered during pregnancy. Health care problems were frequent in all the subjects, especially depression and suicidal ideation. The nonbattered and battered subjects as well as their partners were compared with respect to several demographic variables. There was a statistically significant higher rate of reported qualities of machismo among batterers when compared with nonbatterers. Recommendations include suggestions for further research.

Comparison of the hospital cost of primary and revision total hip arthroplasty after cost containment.

This study compared the hospital cost of primary and revision total hip arthroplasty (THA) after the introduction of cost-containment programs (clinical pathway, hip implant standardization, and competitive bid purchasing of hip implants). Hospital financial records for 290 primary and 85 revision THAs performed from October 1993 through September 1995 were analyzed. A cost-accounting system provided actual hospital cost data for each procedure. Accurate calculation of hospital income or loss was determined. Average hospital length of stay was 4.9 days for primary THA and 5.9 days for revision THA. Average hospital cost was $11,104 for primary THA and $14,935 for revision THA. Average net income (hospital revenue hospital expense) for primary THA was $2486. Average loss from revision THA was $401. The payer mix included commercial insurance, Blue Cross/Blue Shield, managed care, Medicare, Medicaid, and workmen's compensation. For primary THA, all payers were profitable except Medicaid and selected managed care contracts. For revision THA, profit was achieved with payment from commercial insurance only. Despite the introduction of cost-containment programs, revision THA did not achieve profitability at our institution.