Vibrational properties of anhydrous and partially hydrated uranyl fluoride.

Uranyl fluoride (UO2F2) is a hygroscopic powder with two main structural phases: an anhydrous crystal and a partially hydrated crystal of the same R3¯m symmetry. The formally closed-shell electron structure of anhydrous UO2F2 is amenable to density functional theory calculations. We use density functional perturbation theory (DFPT) to calculate the vibrational frequencies of the anhydrous crystal structure and employ complementary inelastic neutron scattering and temperature-dependent Raman scattering to validate those frequencies. As a model closed-shell actinide, we investigated the effect of LDA, GGA, and non-local vdW functionals as well as the spherically averaged Hubbard +U correction on vibrational frequencies, electronic structure, and geometry of anhydrous UO2F2. A particular choice of Ueff=5.5 eV yields the correct U-Oyl bond distance and vibrational frequencies for the characteristic Eg and A1g modes that are within the resolution of experiment. Inelastic neutron scattering and Raman scattering suggest a degree of water coupling to the lattice vibrations in the more experimentally accessible partially hydrated UO2F2 system, with the symmetric stretching vibration shifted approximately 47 cm-1 lower in energy compared to the anhydrous structure. Evidence of water interaction with the uranyl ion is present from a two-peak decomposition of the uranyl stretching vibration in the Raman spectra and anion-hydrogen stretching vibrations in the inelastic neutron scattering spectra. A first-order dehydration phase transition temperature is definitively identified to be 125 °C using temperature-dependent Raman scattering.

Development of an ELISA for the Pharmacokinetic Evaluation of a Murine Anti CD66 Monoclonal Antibody in Human Serum.

An enzyme-linked immunosorbent assay (ELISA) was needed to assist in the pharmacokinetic evaluation of the murine antibody conjugate CHX A" DTPA Besilesomab in serum samples in a clinical trial . A search failed to locate a validated assay that quantified murine antibodies in human serum so the purpose of this article was to develop a robust assay, validated against current guidelines. A detailed method for an ELISA to measure a murine antibody in human serum is described. The assay was validated as fit for purpose against the target values of coefficient of variation < 20% and accuracy ± 20%.

Occupational hazard: radiation exposure for the urologist--developing a reference standard.

INTRODUCTION: To date, there is a paucity of literature offering practicing urologists a reference for the amount of radiation exposure received while surgically managing urolithiasis. This study examines the cumulative radiation exposure of an urologist over 9 months. MATERIALS AND METHODS: We present a case series of fluoroscopic exposures of an experienced stone surgeon operating at an academic comprehensive stone center between April and December 2011. Radiation exposure measurements were determined by a thermoluminescent dosimeter worn on the outside of the surgeon's thyroid shield. Estimations of radiation exposure (mrem) per month were charted with fluoroscopy times, using scatter plots to estimate Spearman's rank correlation coefficients. RESULTS: The total 9-month radiation exposure was 87 mrems for deep dose equivalent (DDE), 293 mrem for lens dose equivalent (LDE), and 282 mrem for shallow dose equivalent (SDE). Total fluoroscopy time was 252.44 minutes for 64 ureteroscopies (URSs), 29 percutaneous nephrolithtomies (PNLs), 20 cystoscopies with ureteral stent placements, 9 shock wave lithotripsies (SWLs), 9 retrograde pyelograms (RPGs), 2 endoureterotomies, and 1 ureteral balloon dilation. Spearman's rank correlation coefficients examining the association between fluoroscopy time and radiation exposure were not significant for DDE (p = 0.6, Spearman's rho = 0.2), LDE (p = 0.6, Spearman's rho = 0.2), or SDE (p = 0.6, Spearman's rho = 0.2). CONCLUSIONS: Over a 9-month period, total radiation exposures were well below annual accepted limits (DDE 5000 mrem, LDE 15,000 mrem and SDE 50,000 mrem). Although fluoroscopy time did not correlate with radiation exposure, future prospective studies can account for co-variates such as patient obesity and urologist distance from radiation source.

Behavioural digital biomarkers enable real-time monitoring of patient-reported outcomes: a substudy of the multicenter, prospective observational SafeHeart study.

INTRODUCTION: Patient-reported outcome measures (PROMs) serve multiple purposes, including shared decision-making and patient communication, treatment monitoring and health-technology assessment. Patient monitoring using PROMs is constrained by recall and non-response bias, respondent burden and missing data. We evaluated the potential of behavioural digital biomarkers obtained from a wearable accelerometer to achieve personalised predictions of PROMs. METHODS: Data from the multicenter, prospective SafeHeart study conducted at Amsterdam University Medical Center in the Netherlands and Copenhagen University Hospital, Rigshospitalet in Copenhagen, Denmark, was used. The study enrolled patients with an implantable cardioverter defibrillator (ICD) between May 2021 and September 2022 who then wore wearable devices with raw acceleration output to capture digital biomarkers reflecting physical behaviour. To collect PROMs, patients received the KCCQ and EQ5D-5 L questionnaire at two instances; baseline and after 6 months. Multivariable Tobit regression models were used to explore associations between digital biomarkers and PROMs, specifically whether digital biomarkers could enable PROM prediction. RESULTS: The study population consisted of 303 patients (mean age 62.9 ± 10.9 years, 81.2% male). Digital biomarkers showed significant correlations to patient-reported physical and social limitations, severity and frequency of symptoms and quality of life. Prospective validation of the Tobit models indicated moderate correlations between the observed and predicted scores for KCCQ (concordance correlation coefficient (CCC) = 0.49, mean difference: 1.07 points) and EQ5D-5 L (CCC = 0.38, mean difference 0.02 points). CONCLUSION: Wearable digital biomarkers correlate with PROMs, and may be leveraged for real-time prediction. These findings hold promise for monitoring of PROMs through wearable accelerometers.

Monobody adapter for functional antibody display on nanoparticles for adaptable targeted delivery applications.

Vascular endothelial cells (ECs) play a central role in the pathophysiology of many diseases. The use of targeted nanoparticles (NPs) to deliver therapeutics to ECs could dramatically improve efficacy by providing elevated and sustained intracellular drug levels. However, achieving sufficient levels of NP targeting in human settings remains elusive. Here, we overcome this barrier by engineering a monobody adapter that presents antibodies on the NP surface in a manner that fully preserves their antigen-binding function. This system improves targeting efficacy in cultured ECs under flow by >1000-fold over conventional antibody immobilization using amine coupling and enables robust delivery of NPs to the ECs of human kidneys undergoing ex vivo perfusion, a clinical setting used for organ transplant. Our monobody adapter also enables a simple plug-and-play capacity that facilitates the evaluation of a diverse array of targeted NPs. This technology has the potential to simplify and possibly accelerate both the development and clinical translation of EC-targeted nanomedicines.

The cysteine-rich domain of human ADAM 12 supports cell adhesion through syndecans and triggers signaling events that lead to beta1 integrin-dependent cell spreading.

The ADAMs (a disintegrin and metalloprotease) family of proteins is involved in a variety of cellular interactions, including cell adhesion and ecto- domain shedding. Here we show that ADAM 12 binds to cell surface syndecans. Three forms of recombinant ADAM 12 were used in these experiments: the cys-teine-rich domain made in Escherichia coli (rADAM 12-cys), the disintegrin-like and cysteine-rich domain made in insect cells (rADAM 12-DC), and full-length human ADAM 12-S tagged with green fluorescent protein made in mammalian cells (rADAM 12-GFP). Mesenchymal cells specifically and in a dose-dependent manner attach to ADAM 12 via members of the syndecan family. After binding to syndecans, mesenchymal cells spread and form focal adhesions and actin stress fibers. Integrin beta1 was responsible for cell spreading because function-blocking monoclonal antibodies completely inhibited cell spreading, and chondroblasts lacking beta1 integrin attached but did not spread. These data suggest that mesenchymal cells use syndecans as the initial receptor for the ADAM 12 cysteine-rich domain-mediated cell adhesion, and then the beta1 integrin to induce cell spreading. Interestingly, carcinoma cells attached but did not spread on ADAM 12. However, spreading could be efficiently induced by the addition of either 1 mM Mn(2+) or the beta1 integrin-activating monoclonal antibody 12G10, suggesting that in these carcinoma cells, the ADAM 12-syndecan complex fails to modulate the function of beta1 integrin.

A global geometric framework for nonlinear dimensionality reduction.

Scientists working with large volumes of high-dimensional data, such as global climate patterns, stellar spectra, or human gene distributions, regularly confront the problem of dimensionality reduction: finding meaningful low-dimensional structures hidden in their high-dimensional observations. The human brain confronts the same problem in everyday perception, extracting from its high-dimensional sensory inputs-30,000 auditory nerve fibers or 10(6) optic nerve fibers-a manageably small number of perceptually relevant features. Here we describe an approach to solving dimensionality reduction problems that uses easily measured local metric information to learn the underlying global geometry of a data set. Unlike classical techniques such as principal component analysis (PCA) and multidimensional scaling (MDS), our approach is capable of discovering the nonlinear degrees of freedom that underlie complex natural observations, such as human handwriting or images of a face under different viewing conditions. In contrast to previous algorithms for nonlinear dimensionality reduction, ours efficiently computes a globally optimal solution, and, for an important class of data manifolds, is guaranteed to converge asymptotically to the true structure.

A prospective longitudinal study to assess psychological changes following anterior cruciate ligament reconstruction surgery.

OBJECTIVE: To determine whether the psychological characteristics of athletes who have undergone an anterior cruciate ligament (ACL) reconstruction change during rehabilitation are related to returning to competitive sport. DESIGN: Prospective longitudinal study. METHOD: 87 athletes completed the Emotional Response of Athletes to Injury Questionnaire (ERAIQ) and the ACL Return to Sport after Injury scale (ACL-RSI) at 3, 6 and 12 months following ACL reconstruction surgery. Physical outcome measures were also taken at each time point. RESULTS: At 12 months 44 (51%) participants had returned to competitive sport and 43 (49%) participants had not returned. There were no differences in physical recovery or scores on the ERAIQ between the two groups. Participants who had returned to competitive sport at 12 months, however, scored significantly higher on the ACL-RSI scale (reflecting a more positive psychological response about sport participation) at both 6 and 12 months than participants who had not returned to competitive sport. CONCLUSIONS: During rehabilitation there are significant psychological differences regarding sport resumption between athletes who do, and do not, resume competitive sport 12 months following ACL reconstruction. These differences occur as early as 6 months postoperatively and highlight the importance of addressing all aspects of an athlete's recovery in order to help facilitate the athlete returning to sport.

The distribution of general dental practitioners with NHS contract numbers in relation to the distance of their practices from the seven dental undergraduate teaching hospitals in England outside London.

OBJECTIVE: To examine whether the presence of a dental school acts as an influence on the number of dentists practicing in the surrounding area. RESEARCH DESIGN: The project used Geographical Information Systems (GIS) mapping techniques, along with data on the location of NHS dentists, to plot dentist to population rates at selected distances from dental undergraduate teaching hospitals in England. A GIS map of dentist to population rates was then constructed for each of the dental schools and the rate patterns examined and compared. RESULTS: With the exception of Liverpool, the maps demonstrated higher than average rates up to two miles, and up to five miles for Manchester, from the location of the dental school before falling and then varying around the England and Wales average. No clear pattern emerged between dental schools, and no two schools produced a similar 'footprint'. CONCLUSIONS: Within the constraints of the current study, it appears that for graduates from the seven dental undergraduate teaching hospitals in England outside London, who work as general dental practitioners with NHS contracts, factors other than the distance of a practice from their place of training appear to have a greater influence on their choice of geographical location where they work, than its distance from a dental hospital.

Effects of pore structure and molecular size on diffusion in chromatographic adsorbents.

Two computational approaches, namely Brownian dynamics and network modeling, are presented for predicting effective diffusion coefficients of probes of different sizes in three chromatographic adsorbents, the structural properties of which were determined previously using electron tomography. Three-dimensional reconstructions of the adsorbents provide detailed, explicit characteristics of the pore network, so that no assumptions have to be made regarding pore properties such as connectivity, pore radius and pore length. The diffusivity predictions obtained from the two modeling approaches were compared to experimental diffusivities measured for dextran and protein probes. Both computational methods captured the same qualitative results, while their predictive capabilities varied among adsorbents.

Attitudes and opinions of NHS general dental practitioners towards clinical governance.

AIM: To assess the attitudes and opinions of NHS general dental practitioners towards clinical governance. DESIGN: This was a questionnaire based study, sent to NHS principal dentists within the West Midlands area. METHOD: A Likert scale questionnaire was developed, consisting of 26 statements in four subject areas. It was internally and externally validated, and sent to 208 practices within four geographic areas. RESULTS: A total of 150 questionnaires were returned; a response rate of 72%. For each question, no significant difference was found between areas. The cost and time involved with clinical governance emerged as the most important issues, with many respondents considering that costs of implementation might make more dentists leave the NHS. Dentists were largely positive about the principles of clinical governance and evidence based practice, but were concerned about the possibility of increasing complaints and some doubted that it would result in improved patient care. Many respondents claimed to be still confused about clinical governance and the majority considered that more guidance should be available to assist with development within dental practice. CONCLUSIONS: This survey showed that some problems exist around the introduction of clinical governance within NHS general dental practice.

Asbestosis. Bronchoalveolar lavage fluid proteins and their relationship to pulmonary epithelial permeability.

We measured levels of albumin and immunoglobulins in serum and bronchoalveolar lavage (BAL) fluid in 28 men with asbestosis and 11 control subjects. The half-time clearance of inhaled diethylene triamine pentacetate labelled with technetium-99m (99mTc-DTPA) from the lungs (t1/2LB) was measured in 26 patients with asbestosis and in 31 normal nonsmoking controls. In those individuals in whom immunoglobulins were detected in BAL fluid, the mean IgG:albumin ratio in BAL fluid was 0.30 (range, 0.11 to 0.97), significantly less than the ratio of 0.43 (0.28 to 0.66) in control subjects (p less than 0.05). There was no significant difference in IgA:albumin ratios between patients and control subjects. The mean BAL:serum albumin ratio in patients with asbestosis was 2.3 X 10(-3) (range, 0.2 to 9.5 X 10(-3), significantly greater than the ratio of 1.2 X 10(-3) (0.5 to 2.0 X 10(-3] in control subjects (p less than 0.02). The t1/2LB was significantly shorter in both smokers and nonsmokers with asbestosis, compared with 31 normal nonsmoking controls, but there were no relationships between t1/2LB and BAL:serum albumin ratio or any other BAL protein levels in either smokers or nonsmokers with asbestosis.

Ritleng intubation system for treatment of congenital nasolacrimal duct obstruction.

Twenty-eight patients (34 eyes) with congenital nasolacrimal duct obstruction underwent silicone intubation with the Ritleng lacrimal intubation system. The technique involves introduction of a Prolene (Ethicon Inc, Somerville, NJ) monofilament guide thread, securely fastened to the silicone tubing, into a tubular metal probe that opens into the inferior meatus. The outcome was evaluated in terms of ease of intubation and objective success rate. Thirty-two (94%) of the 34 lacrimal systems were successfully intubated with the Ritleng system. Difficulty passing the Prolene thread through the probe and out the tip, necessitating conversion to a Crawford intubation system, was encountered in only 2 eyes (6%). The Prolene spontaneously emerged from the nose in 24 (75%) of 32 eyes, making retrieval simple and uncomplicated. The success rate for relieving signs and symptoms of obstruction was 97% (31/32) for the eyes with the Ritleng system and 100% (2/2) for the eyes with the Crawford system. Bicanalicular silicone intubation with the Ritleng intubation system is an easy and effective technique for treatment of congenital nasolacrimal duct obstruction.

Frozen section--guided surgical debridement for management of rhino-orbital mucormycosis.

PURPOSE: To present a new method of surgical treatment for rhino-orbital mucormycosis. METHOD: We treated a patient with extensive surgical debridement of mucormycosis with intraoperative frozen section guidance. The patient did not require exenteration. RESULT: Our patient survived with normal vision and no diplopia. CONCLUSIONS: Frozen section-guided surgical debridement in rhino-orbital mucormycosis may provide an alternative to traditional radical surgical excision. In selected cases, this new method of treatment may cause less morbidity than do traditional treatments.

Effect of thyroid hormone on the myosin heavy chain isoforms in slow and fast muscles of the rat.

The myosin heavy chain (MHC) was studied by biochemical methods in the slow-twitch (soleus) and two fast-twitch leg muscles of the triiodothyronine treated (hyperthyroid), thyroidectomized (hypothyroid) and euthyroid (control) rats. The changes in the contents of individual MHC isoforms(MHC-1, MHC-2A, MHC-2B and MHC-2X) were evaluated in relation to the muscle mass and the total MHC content. The MHC-1 content decreased in hyperthyreosis, while it increased in hypothyreosis in the soleus and in the fast muscles. The MHC-2A content increased in hyperthyreosis and it decreased in hypothyreosis in the soleus muscle. In the fast muscles hyperthyreosis did not affect the MHC-2A content, whereas hypothyreosis caused an increase in this MHC isoform content. The MHC-2X, present only in traces or undetected in the control soleus muscle, was synthesised in considerable amount in hyperthyreosis; in hypothyreosis the MHC-2X was not detected in the soleus. In the fast muscles the content of MHC-2X was not affected by any changes in the thyroid hormone level. The MHC-2B seemed to be not influenced by hyperthyreosis in the fast muscles, whereas the hypothyreosis caused a decrease of its content. In the soleus muscle the MHC-2B was not detected in any groups of rats. The results suggest that the amount of each of the four MHC isoforms expressed in the mature rat leg muscles is influenced by the thyroid hormone in a different way. The MHC-2A and the MHC-2X are differently regulated in the soleus and in the fast muscles; thyroid hormone seems to be necessary for expression of those isoforms in the soleus muscle.

Economic impact of increased clinical intervention rates in community pharmacy. A randomised trial of the effect of education and a professional allowance.

OBJECTIVE: To determine the economic impact of an interventional programme aimed to increase the rate of clinical interventions undertaken in community pharmacy. STUDY DESIGN AND PERSPECTIVE: A randomised controlled trial of 4 parallel groups of pharmacies, conducted from a government perspective. Economic evaluations were based on savings/costs attributable to healthcare costs avoided, healthcare costs incurred by the pharmacists' actions, change in medication costs, pharmacy time and telephone calls made by the pharmacist. The study was conducted during November and December 1996 and costings were based on 1997 figures. INTERVENTIONS: A professional fee-for-service [10 Australian dollars ($A; $A1 = 6.50 US dollars) per intervention] and education (an intensive 1-week course or advanced education) were implemented in an attempt to increase clinical interventions by the pharmacists. Group A pharmacies (n = 10) served as a control group and received neither education nor remuneration; group B received education and professional remuneration (n = 9); group C had received prior continued education and now received advanced education and professional remuneration (n = 11); and group D received professional remuneration with no education. MAIN OUTCOME MEASURES AND RESULTS: The proactive clinical interventions in group C saved a mean of $A85.35 per 1000 prescriptions [95% confidence interval (CI)-$A157.11 to $A24.95). This was 4 times greater than savings generated by pharmacies in group B (mean savings of $A25.65 per 1000 prescriptions) and 6 times greater than control pharmacies. A sensitivity analysis which extrapolated results to Australian prescription figures showed that the control group was capable of generating savings in the order of $A2.4 million per year while pharmacists in group C would save the healthcare system $A15 million per year. CONCLUSIONS: These results provide the first economic estimates for the provision of clinical interventions in Australian community pharmacies. It is believed that they illustrate the value of pharmaceutical services to the healthcare system and to the Australian community in terms of both quality of care and savings.

Thin malignant melanomas of the head and neck.

Historically, Breslow classified thin melanomas as invasive lesions less than 0.76 mm in depth with rare instances of recurrence and mortality. From 1970 to 1990, 87 patients with thin head and neck melanoma were treated at Duke Medical Center. A computer-aided retrospective analysis was performed. Recurrence occurred in 30% of these patients; however, of the 66 patients seen at this institution prior to recurrence, only 8% recurred. Recurrence significantly shortened survival. Compared to an overall 84% 5-year survival, there was less than a 50% 5-year survival after recurrence. For thin melanomas, thickness did not affect survival. There was no difference in survival between thin melanomas and those ranging from 0.76 to 1.5 mm. A multivariate analysis was performed. The data suggest that thin melanomas of the head and neck may recur at a higher rate than previously reported and in addition, that they can be lethal.

Pulmonary epithelial permeability: vascular background effects on whole lung and regional half-time values.

Pulmonary epithelial permeability was first measured by Jones et al. We have adapted their technique for use with a gamma camera. Both regional half-time values and background correction factors vary from apex to base in the lung. Examination of two methods of background correction show: that inter-segmental half-time comparison is possible without applying individual correction factors to regions. the use of a region of interest with similar vascular supply to that of the lung eliminates the need for a background correction technique that relies upon an intravenous injection of radioisotope. The inter-renal area provides such a vascular area.

Technetium-99m-glucoheptonate lung imaging; has it a role in the diagnosis of bronchial carcinoma?

It has been shown by Vorne et al. and Passamonte et al. that technetium-99m-glucoheptonate (Tc-GH) concentrates in bronchial carcinomas. The two studies reported similar sensitivities (88 and 91%, respectively) but discordant specificities (88 and 10%, respectively). In order to assess the uptake of Tc-GH in bronchial carcinomas we performed lung imaging on patients with an abnormal chest radiograph who were undergoing routine investigations for bronchial carcinoma. 108 patients (85 carcinoma, 23 non-carcinoma) were given 555 MBq (15 mCi) Tc-GH intravenously and scanned 5 h later. Images were assessed by one investigator (J.A.L.) without knowledge of the patient's clinical details or other results. Localized uptake of Tc-GH was seen in 71 out of 85 patients who proved to have bronchial carcinoma. Uptake was also seen in 16 out of 23 patients with a variety of non-malignant lung conditions. Sensitivity for bronchial carcinoma was 84%, and specificity 30%. Uptake did not vary significantly with histology. Eleven out of 12 patients with proven tuberculosis had increased uptake of Tc-GH; two of those patients also had inactive lesions which did not concentrate the tracer. In conclusion, Tc-GH is of limited value in the diagnosis of bronchial carcinoma, because of its low specificity. A possible role in the diagnosis of active tuberculosis may exist, following further assessment.

Drowning fatalities of children in Tasmania: differences from national data.

All drownings of people under 15 years of age in Tasmania from 1981 to 1993 were identified from the Tasmanian coroner's case files. Age- and sex-specific mortality rates were calculated and found to be similar to Australian drowning mortality rates. An exception was the lower drowning rate for Tasmanian females aged 0 to 4 years. Only 9 per cent of drowning deaths were caused by immersion in a swimming pool, 32 per cent of deaths occurred in dams and ponds and 21 per cent occurred in a river. Most drownings (88 per cent) associated with dams, ponds, swimming pools and baths were in the 0-to-4-year age group. Compared with Australia as a whole, toddlers drowning in swimming pools is uncommon in Tasmania; however, there are relatively more drownings in dams and ponds. Strategies for the prevention of drowning in childhood in Tasmania should consider the hazards associated with rural living.