Development of a reference material for analysing naturally occurring radioactive material from the steel industry.

Accurate measurement of naturally occurring radionuclides in blast furnace slag, a by-product of the steel industry, is required for compliance with building regulations where it is often used as an ingredient in cement. A matrix reference blast furnace slag material has been developed to support traceability in these measurements. Raw material provided by a commercial producer underwent stability and homogeneity testing, as well as characterisation of matrix constituents, to provide a final candidate reference material. The radionuclide content was then determined during a comparison exercise that included 23 laboratories from 14 countries. Participants determined the activity per unit mass for 226Ra, 232Th and 40K using a range of techniques. The consensus values obtained from the power-moderated mean of the reported participant results were used as indicative activity per unit mass values for the three radionuclides: A0(226Ra) = 106.3 (34) Bq·kg-1, A0(232Th) = 130.0 (48) Bq·kg-1 and A0(40K) = 161 (11) Bq·kg-1 (where the number in parentheses is the numerical value of the combined standard uncertainty referred to the corresponding last digits of the quoted result). This exercise helps to address the current shortage of NORM industry reference materials, putting in place infrastructure for production of further reference materials.

Buckling without Bending: A New Paradigm in Morphogenesis.

A curious feature of organ and organoid morphogenesis is that in certain cases, spatial oscillations in the thickness of the growing "film" are out of phase with the deformation of the slower-growing "substrate," while in other cases, the oscillations are in phase. The former cannot be explained by elastic bilayer instability, and contradict the notion that there is a universal mechanism by which brains, intestines, teeth, and other organs develop surface wrinkles and folds. Inspired by the microstructure of the embryonic cerebellum, we develop a new model of 2D morphogenesis in which system-spanning elastic fibers endow the organ with a preferred radius, while a separate fiber network resides in the otherwise fluidlike film at the outer edge of the organ and resists thickness gradients thereof. The tendency of the film to uniformly thicken or thin is described via a "growth potential." Several features of cerebellum, +blebbistatin organoid, and retinal fovea morphogenesis, including out-of-phase behavior and a film thickness amplitude that is comparable to the radius amplitude, are readily explained by our simple analytical model, as may be an observed scale invariance in the number of folds in the cerebellum. We also study a nonlinear variant of the model, propose further biological and bioinspired applications, and address how our model is and is not unique to the developing nervous system.

Angiogenin promotes tumoral growth and angiogenesis by regulating matrix metallopeptidase-2 expression via the ERK1/2 pathway.

Tumor angiogenesis is essential for tumor growth and metastasis and is dependent on key angiogenic factors. Angiogenin (ANG), a 14.2-kDa polypeptide member of the RNase A superfamily, is an angiogenic protein that has been reported to be upregulated and associated with poor prognosis in some human cancers. The mechanisms through which aberrant ANG levels promote specific steps in tumor progression are unknown. Here, we show that ANG expression in human tissues is strongly correlated with an invasive cancer phenotype. We also show that ANG induces cellular survival, proliferation, endothelial tube formation and xenograft angiogenesis and growth. Novel mechanistic investigations revealed that ANG expression stimulated matrix metallopeptidase-2 (MMP2) expression through the phosphorylation of ERK1/2. Targeting ANG in vivo with N65828, a small-molecule inhibitor of the ribonucleolytic activity of human ANG, resulted in the diminution of xenograft tumoral growth through the inhibition of angiogenesis. Our findings support an unrecognized interplay between ANG, ERK1/2 and MMP2 that can impact tumor growth and progression. The targeting of ANG and associated factors could provide a novel strategy to inhibit tumor establishment and growth.

The value of health libraries and librarians to the Irish health system.

Librarians working in the Irish health sector are under threat. This is a relatively young profession in comparison with international counterparts, with a low staffing base even at its peak. The public sector moratorium has led to professionally qualified librarians and library assistants not being replaced right across the health system. Librarians are employed in the HSE, voluntary sector, and university sectors. The value that this profession brings to healthcare has been documented in systematic reviews and literature in other countries. In Ireland this group is represented by the Health Science Libraries Group (HSLG), a section of the Library Association of Ireland. The HSLG commissioned research into the status of the profession as well as Irish health libraries. This resulted in the publication of the "SHeLLI Report" in 2011. Results of the report are outlined here and selected examples of value of librarians to healthcare are described.

Development of a health care personnel handwash with 6-hour persistence.

BACKGROUND: Health care handwashes/sanitizers help prevent the spread of infection. Many are alcohol-based, providing immediate microbial kill. Few contain persistence factors for residual antimicrobial effects. We conducted multiple studies on Viacydin-Containing Alcohol Sanitizer (VCAS) to evaluate antimicrobial properties and skin friendliness. METHODS: The potential of VCAS to cause use related skin problems was examined by repeated applications over a 3-week period. Excessive handwashing compared effects of VCAS on the skin barrier with that of other handwash products. Antimicrobial range, immediate kill rates, and resistance development were assessed as was the potential for continued antimicrobial activity over an extended period following product use. RESULTS: Our data showed the VCAS formula has broad, rapid antimicrobial efficacy without promoting microbial resistance. VCAS is mild to skin. Antimicrobial persistence testing showed that VCAS remained effective up to 6 hours postapplication. CONCLUSION: VCAS was superior to or at parity with on-market products, exhibited substantial residual effects and persistence up to 6 hours, and was safe and well tolerated. These results provide strong evidence for the value of VCAS to help prevent and eliminate pathogen contamination of the hands.

A unique water optional health care personnel handwash provides antimicrobial persistence and residual effects while decreasing the need for additional products.

BACKGROUND: The Centers for Disease Control and Prevention (CDC) has published guidelines for hand hygiene practices, recommending a handwash regimen that alternates between waterless alcohol products and antimicrobial or nonantimicrobial soap and water. The advent of an alcohol-based product that can be used with or without water (ie, water optional) to decontaminate the hands while providing immediacy of kill and antimicrobial persistence could reduce the confusion associated with handwash guidelines. Such a product has been developed, is alcohol-based (61%), and zinc pyrithione (ZPT) preserved (61% alcohol-ZPT) and has proven to be fully compliant with the Food and Drug Administration (FDA) and CDC guidelines. METHODS: FDA-required testing of the 61% alcohol-ZPT product for the health care personnel handwash indication was performed as outlined in the Tentative Final Monograph (TFM) for Health-Care Antiseptic Drug Products, employing waterless and water-aided product applications. It was next assessed for antimicrobial persistence and residual effects by comparing it, in separate waterless and water-aided applications, with commonly available handwashes containing various antimicrobials in a 5-day study employing 49 subjects, in which samples were collected immediately and at 4 hours and 8 hours postapplication. The skin conditioning properties of this formulation were investigated via appropriate methods. RESULTS: The 61% alcohol-ZPT product easily produced >3.0 log 10 reduction in the indicator strain ( Serratia marcescens ) following the first wash, exceeding the 2.0 log 10 FDA requirement. This level of performance was maintained through the tenth wash, surpassing the 3.0 log 10 FDA requirement for the handwash indication. For the assessment of persistence and residual effect in the waterless mode, the water-optional, 61% alcohol-ZPT product consistently produced log 10 reductions of nearly 3.5 or greater at every point over the entire study period. In the water-aided configuration, similar results were obtained as log 10 reductions of 2.5 were observed. The formulation is nonirritating, actually contributing to hand skin condition. CONCLUSIONS: The 61% alcohol-ZPT product exceeds all FDA criteria for the health care personnel handwash indication and is a significant advancement in the concept of skin antisepsis. It represents a single product suitable for use in all hand hygiene settings, demonstrating improved antimicrobial persistence and residual effects. The 61% alcohol-ZPT formulation contributes positively to overall hand conditioning, and a previously reported study has documented it to be virucidal for several DNA and RNA viruses.

Zinc pyrithione in alcohol-based products for skin antisepsis: persistence of antimicrobial effects.

Alcohol-based products for skin antisepsis have a long history of safety and efficacy in the United States and abroad. However, alcohol alone lacks the required antimicrobial persistence to provide for the sustained periods of skin antisepsis desired in the clinical environment. Therefore, alcohol-based products must have a preservative agent such as iodine/iodophor compounds, chlorhexidine gluconate, or zinc pyrithione, to extend its antimicrobial effects. Iodine, iodophors, and chlorhexidine gluconate are well-characterized antimicrobials and preservatives. The thrust of our effort was to examine the characteristics of the lesser-known zinc pyrithione and to evaluate its utility as a preservative in the formulation of alcohol-based products for skin antisepsis. This work includes a literature review of current zinc pyrithione applications in drugs and cosmetics, a safety and toxicity evaluation, consideration of the proposed mechanisms of antimicrobial action, in vitro and in vivo efficacy data, and a discussion of the mechanisms that confer the desired antimicrobial persistence. In addition, alcohol-based, zinc pyrithione-preserved, commercially available products of skin antisepsis are compared with other commercially available antimicrobials used for skin antisepsis and with additional alcohol-based products with different preservatives. The authors' conclusion is that zinc pyrithione is not only a safe and effective antimicrobial but that its use in certain alcohol-based formulations results in antimicrobial efficacy exceeding that of iodine and chlorhexidine gluconate.

A systems approach to preoperative surgical patient skin preparation.

BACKGROUND: The merits of a systems approach to preoperative surgical patient skin preparation are presented. A "system" may be defined as the addition of an antiseptic bath(s) or shower(s) within 24 hours before the application of a Food and Drug Administration-compliant patient preoperative skin preparation at the time of surgery. The expected outcome from this added effort is a further reduction in the transient and normal flora that contaminate the skin surrounding the operative site, and contribute to surgical infections. The Centers for Disease Control and Prevention has recommended the addition of this step to the preoperative site preparation regimen. METHODS: A human in vivo study comparing an alcohol-based (ethanol) system to an iodine-based approach, and 2 sets of clinical observations, are presented here. RESULTS: The data confirm the utility of the systems approach. The in vivo study demonstrates that significant reductions (> or =2 log(10)) in normal and transient flora can be achieved quickly and maintained out to 72 hours after the surgery, allowing for wound closure in a prolonged state of skin antisepsis. Clinical observations support the in vivo findings. After initiation of the system, the infection rates for the monitored procedures have decreased. CONCLUSIONS: The data presented here delineate the merits of a systems approach to preoperative surgical patient skin preparation. This approach has a positive impact on infection rates and may reduce the additional costs associated with this preventable event.

Recurrent pneumococcal arthritis as the presenting manifestation of X-linked agammaglobulinemia.

Pneumococcal arthritis in children older than 24 months is unusual and can suggest underlying immunodeficiency. We report a case of recurrent pneumococcal arthritis as the presenting manifestation of X-linked agammaglobulinemia.

Muscle abnormalities in juvenile dermatomyositis patients: P-31 magnetic resonance spectroscopy studies.

OBJECTIVE: To characterize metabolic abnormalities in the muscles of children with the juvenile variant of dermatomyositis (JDM) by the use of noninvasive P-31 magnetic resonance spectroscopy (MRS). METHODS: Thirteen patients with JDM (ages 4-16 years) were studied. Biochemical status was evaluated with P-31 MRS by determining the concentrations of the high-energy phosphate compounds, ATP and phosphocreatine (PCr), ratios of inorganic phosphate (Pi) to PCr (Pi:PCr ratio), levels of free cytosolic ADP, and phosphorylation potentials (PPs) during rest, exercise, and recovery. RESULTS: Significant metabolic abnormalities were observed in the thigh muscles of 10 severely affected patients during rest, 2 graded levels of exercise, and recovery. Mean ATP and PCr levels in the muscles of JDM patients were 35-40% below the normal control values (P < 0.003). These data, along with elevated Pi:PCr ratios, higher ADP levels, and abnormal values for PPs, indicated defective oxidative phosphorylation in the mitochondria of diseased JDM muscles. MRS findings were normal in 2 additional patients who had improved with prednisone treatment and in 1 patient who had no muscle weakness (amyopathic variant of JDM). CONCLUSION: JDM patients can be monitored with noninvasive P-31 MRS without sedation. Biochemical defects in energy metabolism are concordant with the weakness and fatigue reported by JDM patients. Quantitative MRS data are useful for evaluating patients and optimizing drug treatment regimens.

The role of routine laboratory studies and neuroimaging in the diagnosis of dementia: a clinicopathological study.

OBJECTIVE: To determine the neuropathological diagnoses of longitudinally followed patients with potentially reversible causes of dementia and to examine the results of the "dementia work-up," especially neuroimaging, by comparison with the pathological diagnosis. DESIGN: A neuropathologic series of 61 consecutive patients, with review of clinical, laboratory, neuroimaging, and pathological results. RESULTS: Of the 61 patients, forty-eight (79%) had a clinical diagnosis of probable or possible Alzheimer's disease (AD). Compared with the pathological diagnosis, the sensitivity and specificity of the clinical diagnosis of AD were 96% and 79%, respectively. Of the 61 patients, 9 had abnormal laboratory tests, the correction of which did not improve the subsequent course. These patients were found to have AD8 and frontotemporal dementia on pathology. In two patients, neuroimaging was helpful in the clinical diagnoses of frontotemporal dementia and progressive supranuclear palsy (PSP). Neuroimaging revealed cerebrovascular disease in 18 patients, only two of whom were suspected clinically. Pathology confirmed AD in 17 and PSP in 1 of these patients. Sensitivity and specificity for the clinical diagnosis of cerebrovascular disease in comparison with pathology were 6% and 98%, respectively. With the added information from neuroimaging, that sensitivity increased to 59% and specificity decreased to 81%. CONCLUSIONS: All cases with abnormal laboratory or neuroimaging results had AD or some other neurodegenerative disease on pathology. The "dementia work-up" did not reveal any reversible causes for dementia in this group of patients. Neuroimaging may have a role, especially in the diagnosis of possible AD with concomitant cerebrovascular disease.

Staging and prognostic factors in testicular cancer.

Germ cell cancers of the testis are rare malignancies that occur most commonly in young adult male life. These malignancies are highly curable, and adoption of sophisticated treatment strategies, related to known prognostic-based variables, has resulted in overall cure rates of approximately 95% with acceptable morbidity. These treatment approaches require a thorough knowledge of the underlying pathology and patterns of tumour spread. In recent years a number of prognostic factor-based staging classifications have evolved, each of which can accurately predict prognosis. However, in 1997, an internationally agreed-upon consensus classification applicable to both seminoma and non-seminoma was published. This classification was well validated and has now been incorporated into the TNM and American Joint Committee on Cancer (AJCC) staging systems.

A clinicopathological comparison of community-based and clinic-based cohorts of patients with dementia.

OBJECTIVES: To compare the sensitivity and specificity of the clinical diagnosis of Alzheimer disease, the distribution of pathological causes, and the demographic and clinical characteristics of 2 different groups of patients with dementia. DESIGN: Retrospective clinicopathological study. SETTING: A memory disorder clinic in a university hospital and a multiethnic community. PATIENTS: Sixty-three patients from a memory disorder clinic and 26 patients from a large community-based study who underwent autopsy after clinical evaluation. MAIN OUTCOME MEASURES: Differential distribution of clinical and pathological findings, with clinicopathological correlations. RESULTS: Clinic patients were younger at diagnosis, more educated, and more likely to be white. Of the 63 clinic patients we evaluated, 29 (46%) had a pathological diagnosis of definite AD, 15 (24%) had a diagnosis of mixed AD, and 19 (30%) had a diagnosis of another type of dementia. The pathological diagnoses in the community patients were distributed as follows: 6 (23%) had definite AD, 6 (23%) had mixed AD, 6 (23%) had cerebrovascular disease, and 8 (31%) had another type of dementia. The difference in distribution of pathological diagnoses between these 2 groups was only significant for cerebrovascular diseases. For patients seen at the clinic, the sensitivity of the clinical diagnosis of AD was 98% and the specificity was 84%; for the community group, the sensitivity was 92% and the specificity was 79%. CONCLUSIONS: The difference in sensitivity and specificity of clinical diagnosis was not statistically significant between the groups of clinic patients and community patients. Dementia associated with cerebrovascular disease was more prevalent in the community sample. This difference may be attributable to clinical and demographic differences between the 2 groups.

Periodic fever syndrome in children.

OBJECTIVES: To describe the presentation, clinical course, therapeutic response, and long-term follow-up of patients with a syndrome of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA). STUDY DESIGN: Patients with PFAPA (n = 94) referred over a 10-year period completed a registry form and provided medical records. Follow-up telephone calls were made in late 1997 to determine the persistence of episodes and sequelae. RESULTS: PFAPA episodes lasted 4.8 days (95% confidence interval 4.5 to 5.1) and recurred every 28 days (confidence interval 26 to 30), with a maximal temperature of 40.5 degrees C (confidence interval 40. 4 degrees to 40.6 degrees ). Of the 83 children available for follow-up, 34 no longer had episodes. In the remainder the episodes did not differ in character but recurred less frequently over time. The affected children had no long-term sequelae. Glucocorticoids were highly effective in controlling symptoms. Tonsillectomy and cimetidine treatment were associated with remission in a small number of patients. CONCLUSIONS: PFAPA is a not uncommon cause of periodic fever in children. In some children the syndrome resolves, whereas symptoms in others persist. Long-term sequelae do not develop. The syndrome is easily diagnosed when regularly recurring episodes of fever are associated with aphthous stomatitis, pharyngitis, or cervical adenitis.

The morphogenesis of mouse vallate gustatory epithelium and taste buds requires BDNF-dependent taste neurons.

The developmental absence of brain-derived neurotrophic factor (BDNF) in null mutant mice caused three interrelated defects in the vallate gustatory papilla: sparse innervation, a reduction in the area of the gustatory epithelium, and fewer taste buds. On postnatal day 7, the stunted vallate papilla of bdnf null mutant mice was 30% narrower, the trench walls 35% reduced in area, and the taste buds 75% less abundant compared with wild-type controls. Quantitative assessment of innervation density was carried out to determine if the small trench walls and shortage of taste buds could be secondary consequences of the depletion of gustatory neurons. The diminished gustatory innervation was linearly associated with a reduced trench wall area (r = +0.94) and fewer taste buds (r = +0.96). Residual taste buds were smaller than normal and were innervated by a few surviving taste neurons. We conclude that BDNF-dependent taste neurons contribute to the morphogenesis of lingual gustatory epithelia and are necessary for both prenatal and postnatal mammalian taste bud formation. The gustatory system provides a conspicuous example of impaired sense organ morphogenesis that is secondary to sensory neuron depletion by neurotrophin gene null mutation.

The morphogenesis of mouse vallate gustatory epithelium and taste buds requires BDNF-dependent taste neurons

The developmental absence of brain-derived neurotrophic factor (BDNF) in null mutant mice caused three interrelated defects in the vallate gustatory papilla: sparse innervation, a reduction in the area of the gustatory epithelium, and fewer taste buds. On postnatal day 7, the stunted vallate papilla of bdnf null mutant mice was 30% narrower, the trench walls 35% reduced in area, and the taste buds 75% less abundant compared with wild-type controls. Quantitative assessment of innervation density was carried out to determine if the small trench walls and shortage of taste buds could be secondary consequences of the depletion of gustatory neurons. The diminished gustatory innervation was linearly associated with a reduced trench wall area (r=+0.94) and fewer taste buds (r=+0.96). Residual taste buds were smaller than normal and were innervated by a few surviving taste neurons. We conclude that BDNF-dependent taste neurons contribute to the morphogenesis of lingual gustatory epithelia and are necessary for both prenatal and postnatal mammalian taste bud formation. The gustatory system provides a conspicuous example of impaired sense organ morphogenesis that is secondary to sensory neuron depletion by neurotrophin gene null mutation.

BDNF is required for the normal development of taste neurons in vivo.

The vallate gustatory epithelium of neonatal trkB null mutant mice (-/-) lacked innervation. This prompted the evaluation of null mutant mice corresponding to the three neurotrophin ligands for tyrosine kinase receptor B (TrkB): brain-derived neurotrophic factor (BDNF), neurotrophin (NT)3, NT4. The vallate gustatory epithelium of nt3-/- mice and of nt4-/- mice appeared normal. Only bdnf-/- mice had a vallate papilla that was stunted, sparsely innervated, and lacked up to 98% of its taste buds. All three defects persisted. For example, the vallate papilla of 12-day-old bdnf-/- mice remained markedly less well innervated than the vallate of 7-day-old or newborn bdnf+/+ mice. The foliate taste papillae of neonatal bdnf-/- mice had similar defects. We conclude that the normal development of taste neurons requires BDNF.

Sickle cell and the eye.

Sickle cell anemia and trait are highly prevalent within the African-American and other minority populations in the United States. As treatment modalities improve, these individuals will live longer, increasing the incidence of sickle-related eye disease. As blinding or life-threatening damage may occur to the retina, optic nerve and central nervous system, any nurse involved in the management of sickle cell must be aware of this critical public health issue. Appropriate screening and patient management are vital to the continued quality of life of these patients.