Early Machine-Human Interface around Sepsis Severity Identification: From Diagnosis to Improved Management?

OBJECTIVE: To investigate the statistical measures of the performance of 2 interventions: a) early sepsis identification by a computerized sepsis "sniffer" algorithm (CSSA) in the emergency department (ED) and b) human decision to activate a multidisciplinary early resuscitation sepsis and shock response team (SSRT). METHODS: This study used a prospective and historical cohort study design to evaluate the performance of two interventions. INTERVENTION: A computerized sepsis sniffer algorithm (CSSA) to aid in early diagnosis and a multidisciplinary sepsis and shock response team (SSRT) to improve patient care by increasing compliance with Surviving Sepsis Campaign (SSC) bundles. RESULTS: The CSSA yielded a sensitivity of 100% (95% CI, 99.13-100%) and a specificity of 96.2% (95% CI, 95.55-96.45%) to identifying sepsis in the ED (Table 1). The SSRT resource was activated appropriately in 34.1% (86/252) of patients meeting severe sepsis or septic shock criteria; the SSRT was inappropriately activated only three times in sepsis-only patients. In 53% (134/252) of cases meeting criteria for SSRT activation, the critical care team was consulted as opposed to activating the SSRT resource. CONCLUSION: Our two-step machine-human interface approach to patients with sepsis utilized an outstandingly sensitive and specific electronic tool followed by more specific human decision-making.

IRMM-1000a and IRMM-1000b: uranium reference materials certified for the production date based on the 230Th/234U radiochronometer. Part II: certification.

The IRMM-1000a and IRMM-1000b uranium reference materials, of 20 and 50 mg uranium, respectively, were produced by the European Commission Joint Research Centre's Institute for Reference Materials and Measurements (EC-JRC-IRMM) in collaboration with the Institute for Transuranium Elements (EC-JRC-ITU). They are novel uranium reference materials certified for the production date based on the 230Th/234U radiochronometer, i.e. the date of the last chemical separation of these two radionuclides. The certified reference value and its uncertainty, homogeneity and stability of the material were established in accordance with the ISO Guide 34:2009 and the 'Guide to the Expression of Uncertainty in Measurement'.

Dural ectasia in Marfan's syndrome: magnetic resonance imaging appearances and anaesthetic experience of three deliveries.

Neuraxial anaesthetic techniques are considered useful to minimise haemodynamic stress during labour. In Marfan's syndrome, connective tissue abnormalities not only affect the thoracic aorta but also predispose to dural ectasia. A dural ectatic sac may cause difficulties with neuraxial analgesia and anaesthesia. We discuss magnetic resonance imaging appearances and anaesthetic experience of three deliveries in a parturient with stable echocardiographic findings. We consider that epidural analgesia and anaesthesia are a safe and pragmatic solution for labour and delivery. Lumbo-sacral magnetic resonance imaging at presentation will define dural ectasia and assist in management.

Desenvolvimento do software para monitoração neural em hanseníase

No diagnóstico das lesões neurológicas periféricas é usualmente realizado o exame clínico que consta de mapeamento sensitivo, palpação de nervo e teste de força muscular associado a outros métodos como a avaliação analógica da dor. Todos esses exames podem ser graduados numericamente, constituindo assim um Escore Clínico (EC) para o monitoramento da função neural em estudos longitudinais e análises estatísticas. Atualmente os registros são manuais e anexados ao prontuário do paciente dificultando a organização e visualização em longo prazo da função neural.

Structurally diverse peroxisome proliferator-activated receptor agonists induce apoptosis in human uro-epithelial cells by a receptor-independent mechanism involving store-operated calcium channels.

OBJECTIVES: Peroxisome proliferator-activated receptors (PPARs) are implicated in epithelial cell proliferation and differentiation, but investigation has been confounded by potential off-target effects of some synthetic PPAR ligands. Our aim was to determine mechanisms underlying the pro-apoptotic effect of synthetic PPAR agonists in normal human bladder uro-epithelial (urothelial) cells and to reconcile this with the role of PPARs in urothelial cytodifferentiation. MATERIALS AND METHODS: Normal human urothelial (NHU) cells were grown as non-immortal lines in vitro and exposed to structurally diverse agonists ciglitazone, troglitazone, rosiglitazone (PPARgamma), ragaglitazar (PPARalpha/gamma), fenofibrate (PPARalpha) and L165041 (PPARbeta/delta). RESULTS: NHU cells underwent apoptosis following acute exposure to ciglitazone, troglitazone or ragaglitazar, but not fenofibrate, L165041 or rosiglitazone, and this was independent of ERK or p38 MAP-kinase activation. Pro-apoptotic agonists induced sustained increases in intracellular calcium, whereas removal of extracellular calcium altered the kinetics of ciglitazone-mediated calcium release from sustained to transient. Cell death was accompanied by plasma-membrane disruption, loss of mitochondrial membrane-potential and caspase-9/caspase-3 activation. PPARgamma-mediated apoptosis was unaffected following pre-treatment with PPARgamma antagonist T0070907 and was strongly attenuated by store-operated calcium channel (SOC) inhibitors 2-APB and SKF-96365. CONCLUSIONS: Our results provide a mechanistic basis for the ability of some PPAR agonists to induce death in NHU cells and demonstrate that apoptosis is mediated via PPAR-independent mechanisms, involving intracellular calcium changes, activation of SOCs and induction of the mitochondrial apoptotic pathway.

Differentiation of an auditory neuronal cell line suitable for cell transplantation.

The auditory neuroblast cell line US/VOT-N33 (N33), which is conditionally immortal, was studied as an in vitro model for the differentiation of spiral ganglion neurons (SGNs) and as a candidate for cell transplantation in rodents. It expresses numerous molecular markers characteristic of auditory neuroblasts, including the transcription factors GATA3, NeuroD, Brn3a and Islet1, as well as the neuronal cytoskeletal protein beta3-tubulin. It displays active migratory behaviour in vitro and in vivo. In the presence of the fibroblast growth factors FGF1 or FGF2 it differentiates bipolar morphologies similar to those of native SGNs. In coculture with neonatal cochlear tissue it is repelled from epithelial surfaces but not from native SGNs, alongside which it extends parallel neuronal processes. When injected into the retina in vivo, EGFP-labelled N33 cells were traced for 1-2 weeks and migrated rapidly within the subretinal space. Cells that found their way into the retinal ganglion cell layer extended multiple processes but did not express beta3-tubulin. The ability of N33 to migrate, to differentiate, to localize with native SGNs in vitro and to survive in vivo suggests that they provide an effective model for SGN differentiation and for cell transplantation into the ear.

Assessment of the exposure of islanders to ash from the Soufriere Hills volcano, Montserrat, British West Indies.

BACKGROUND AND AIMS: The Soufriere Hills volcano, Montserrat, has been erupting since July 1995 and volcanic ash has fallen on the island throughout most of the eruption. The ash contains substantial quantities of respirable particles and unusually large amounts (15-20%) of the crystalline silica mineral, cristobalite. The purpose of the surveys described here, undertaken between December 1996 and April 2000, was to determine levels of personal exposure of islanders to volcanic ash and cristobalite in order to inform advice on the associated risks to health and the measures required to reduce exposure. METHODS: Surveys of personal exposure to respirable dust and cristobalite were undertaken using cyclone samplers. In addition, direct reading instruments (DUSTTRAK) were used to monitor ambient air concentrations of PM(10) at fixed sites and also to provide information about exposures to airborne particles associated with selected activities. RESULTS: Environmental concentrations of airborne ash have been greatest in the areas where the most ash has been deposited and during dry weather. Individual exposure to airborne ash was related to occupation, with the highest exposures among gardeners, cleaners, roadworkers, and police at roadside checkpoints. During 1997 many of these individuals were exposed to concentrations of cristobalite that exceeded the ACGIH recommended occupational exposure limit. Since the population became confined to the north of the island in October 1997, even those in relatively dusty occupations have received exposures to cristobalite well below this limit. CONCLUSIONS: Most of the 4500 people who have remained on island since the eruption began have not been exposed to sufficiently high concentrations of airborne dust for long enough to be at risk of developing silicosis. However, more than a dozen individuals continued to experience frequent high occupational exposures to volcanic ash, some of whom may have had sufficient exposure to crystalline silica to be at risk of developing mild silicosis. If volcanic activity were to deposit further ash over the occupied areas of the island during the coming years, the risks of silicosis will become more substantial.

The role of bicarbonate in regulatory volume decrease (RVD) in the epithelial-derived human breast cancer cell line ZR-75-1.

This study investigates the mechanisms involved in the regulatory volume decrease (RVD) in ZR-75-1 epithelial-derived human breast cancer cells. Cell volume changes were measured during osmotic shock using video imaging. In HEPES-buffered hypotonic solutions no RVD was observed; however, RVD was observed in HCO(3)(-)-buffered hypotonic solutions. Inhibition of RVD by 10 microM tamoxifen and 100 microM DIDS (inhibitors of volume-regulated anion channels; VRAC) and 2 mM TEA(+) (inhibitor of K(+) channels) indicates a role for these channels. In HCO(3)(-)-buffered Cl(-)-free solutions RVD was partially abolished indicating that HCO(3)(-) efflux can support RVD but also may have another role. Further experiments investigated whether HCO(3)(-) assists in the accumulation of Cl(-) via Cl(-)-HCO(3)(-) exchange. Regulatory volume increase (RVI) was also HCO(3)(-)-dependent and was inhibited by 500 microM DIDS and 10 microM 5-( N, N-dimethyl)-amiloride (DMA) indicating a role for coupled Cl(-)-HCO(3)(-) and Na(+)-H(+) exchange. Finally, in the presence of 10 microM DMA, RVD was partially inhibited providing further evidence for a role of Cl(-)-HCO(3)(-) exchange. Thus RVD in ZR-75-1 cells involves the activation of VRAC and K(+) channels. RVD is HCO(3)(-)-dependent and HCO(3)(-) efflux through VRAC appears to contribute directly to RVD. HCO(3)(-), however, also has another role in facilitating Cl(-) accumulation via Cl(-)-HCO(3)(-) exchange.

The development and adaptation of the Semmes-Weinstein monofilaments in Brazil.

The purpose of this article is to demonstrate the complexities of adapting technology and developing the sensory testing technique of the Semmes-Weinstein (S-W) monofilaments in Brazil to enable early detection and monitoring of peripheral nerve function in Hansen's disease (Hd). This history of the adoption and implementation of the use of the S-W monofilaments in Brazil follows the sequence described in adoption and diffusion theory of innovations. As a result, the availability of the S-W monofilaments produced in Brazil facilitated the utilization of this sensory testing technique in Brazil. In addition, the Brazilian model proved to be more accessible, durable, portable, and practical in meeting local needs. It improved health care worker awareness of and desire to use better sensory testing technology, making it possible to prevent disability.

Vertically transmitted HIV infection in the British Isles.

OBJECTIVE: To describe the epidemiology of vertically acquired HIV infection in the British Isles, the level of underreporting, the vertical transmission rate, and clinical spectrum of paediatric AIDS. DESIGN: Confidential, linked registers based on reporting from obstetricians and paediatricians; anonymous unlinked neonatal HIV serosurveys. SETTING: British Isles. SUBJECTS: Children born to mothers with HIV infection. MAIN OUTCOME MEASURES: Trends in HIV infection and vertical transmission rate. RESULTS: In Scotland and the Irish Republic, where most maternal HIV infection is related to drug misuse, the annual number of reports of children born to infected mothers has fallen since 1989. In England and Wales nearly half of maternal infections have been acquired overseas, and the number of children born to these women, and to women who became infected in Britain, is increasing. In south east England the proportion of live births to women whose infection was identified before delivery was only 17% (50/287), compared with 68% (26/38) in Scotland. The vertical transmission rate was 13.7% (23/168), and 23% of infected children developed AIDS in the first year of life. 41% (38/92) of children born to infected mothers who were ascertained after delivery were breast fed, compared with 5% (12/236) of those ascertained before delivery. CONCLUSIONS: The incidence of vertically transmitted HIV infection is increasing in England and Wales. More extensive antenatal testing would enable infected women to be counselled against breast feeding, which could prevent a substantial proportion of vertical transmission in some areas, and would increase opportunities for early diagnosis and treatment of infected children.

The development and adaptation of the Semmes-Weinstein monofilaments in Brazil / ?

The purpose of this article is to demonstrate the complexities of adapting technology and developing the sensory testing technique of the Semmes-Weinstein (S-W) monofilaments in Brazil to enable early detection and monitoring of peripheral nerve function in Hansen's disease(Hd). This history of the adoption and implementation of the use of theS-Wmonofilaments in Brazil follows the sequence described in adoption and diffusion theory of innovations.As a result, the availability of the S-W monofilaments produced in Brazil facilitated the utilization of this sensory testing technique in Brazil. In addition, the Brazilian model proved to be more accessible, durable, portable, and practical in meeting local needs. It improved health care worker awareness of and desire to use better sensory testing technology, making it possible to prevent disability

User tests of ear defenders.

Ten different common muff-type ear defenders were tested by 50 potential users for comfort and ease of use. Results showed short-term (3 min) impressions to be a good predictor of long-term comfort; defenders were ranked for comfort and pointers are given for important design features. Only comfortable ear defenders will be worn properly.