140 research outputs found

    An assessment of the Jenkinson and Collison synoptic classification to a continental mid-latitude location

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    A weather-type catalogue based on the Jenkinson and Collison method was developed for an area in south-west Russia for the period 1961--2010. Gridded sea level pressure data was obtained from the National Centers for Environmental Prediction/National Center for Atmospheric Research (NCEP/NCAR) reanalysis. The resulting catalogue was analysed for frequency of individual types and groups of weather types to characterise long-term atmospheric circulation in this region. Overall, the most frequent type is anticyclonic (A) (23.3 {%}) followed by cyclonic (C) (11.9 {%}); however, there are some key seasonal patterns with westerly circulation being significantly more common in winter than summer. The utility of this synoptic classification is evaluated by modelling daily rainfall amounts. A low level of error is found using a simple model based on the prevailing weather type. Finally, characteristics of the circulation classification are compared to those for the original JC British Isles catalogue and a much more equal distribution of flow types is seen in the former classification

    Phase II study of the oxygen saturation curve left shifting agent BW12C in combination with the hypoxia activated drug mitomycin C in advanced colorectal cancer

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    BW12C (5-[2-formyl-3-hydroxypenoxyl] pentanoic acid) stabilizes oxyhaemoglobin, causing a reversible left-shift of the oxygen saturation curve (OSC) and tissue hypoxia. The activity of mitomycin C (MMC) is enhanced by hypoxia. In this phase II study, 17 patients with metastatic colorectal cancer resistant to 5-fluorouracil (5-FU) received BW12C and MMC. BW12C was given as a bolus loading dose of 45 mg kg−1over 1 h, followed by a maintenance infusion of 4 mg kg−1h−1for 5 h. MMC 6 mg m−2was administered over 15 min immediately after the BW12C bolus. The 15 evaluable patients had progressive disease after a median of 2 (range 1–4) cycles of chemotherapy. Haemoglobin electrophoresis 3 and 5 h after the BW12C bolus dose showed a fast moving band consistent with the BW12C-oxyhaemoglobin complex, accounting for approximately 50% of total haemoglobin. The predominant toxicities – nausea/vomiting and vein pain – were mild and did not exceed CTC grade 2. Liver31P magnetic resonance spectroscopy of patients with hepatic metastases showed no changes consistent with tissue hypoxia. The principle of combining a hypoxically activated drug with an agent that increases tissue hypoxia is clinically feasible, producing an effect equivalent to reducing tumour oxygen delivery by at least 50%. However, BW12C in combination with MMC for 5-FU-resistant colorectal cancer is not an effective regimen. This could be related to drug resistance rather than a failure to enhance cytotoxicity. © 2000 Cancer Research Campaig

    Oocyte–Targeted Deletion Reveals That Hsp90b1 Is Needed for the Completion of First Mitosis in Mouse Zygotes

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    Hsp90b1 is an endoplasmic reticulum (ER) chaperone (also named Grp94, ERp99, gp96,Targ2, Tra-1, Tra1, Hspc4) (MGI:98817) contributing with Hspa5 (also named Grp78, BIP) (MGI:95835) to protein folding in ER compartment. Besides its high protein expression in mouse oocytes, little is known about Hsp90b1 during the transition from oocyte-to-embryo. Because the constitutive knockout of Hsp90b1 is responsible for peri-implantation embryonic lethality, it was not yet known whether Hsp90b1 is a functionally important maternal factor.To circumvent embryonic lethality, we established an oocyte-specific conditional knockout line taking advantage of the more recently created floxed Hsp90b1 line (Hsp90b1(flox), MGI:3700023) in combination with the transgenic mouse line expressing the cre recombinase under the control of zona pellucida 3 (ZP3) promoter (Zp3-cre, MGI:2176187). Altered expression of Hsp90b1 in growing oocytes provoked a limited, albeit significant reduction of the zona pellucida thickness but no obvious anomalies in follicular growth, meiotic maturation or fertilization. Interestingly, mutant zygotes obtained from oocytes lacking Hsp90b1 were unable to reach the 2-cell stage. They exhibited either a G2/M block or, more frequently an abnormal mitotic spindle leading to developmental arrest. Despite the fact that Hspa5 displayed a similar profile of expression as Hsp90b1, we found that HSPA5 and HSP90B1 did not fully colocalize in zygotes suggesting distinct function for the two chaperones. Consequently, even if HSPA5 was overexpressed in Hsp90b1 mutant embryos, it did not compensate for HSP90B1 deficiency. Finally, further characterization of ER compartment and cytoskeleton revealed a defective organization of the cytoplasmic region surrounding the mutant zygotic spindle.Our findings demonstrate that the maternal contribution of Hsp90b1 is critical for the development of murine zygotes. All together our data indicate that Hsp90b1 is involved in unique and specific aspects of the first mitosis, which brings together the maternal and paternal genomes on a single spindle

    Crash characteristics and patterns of injury among hospitalized motorised two-wheeled vehicle users in urban India

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    <p>Abstract</p> <p>Background</p> <p>Traffic crashes and consequent injuries represent a growing public health concern in India, particularly in light of increasing motorization. Motorised two-wheeled vehicles (MTV) constitute a large portion of the vehicle fleet in India. We report the crash characteristics and injury patterns among a cohort of MTV riders and pillions presenting to hospital post-crash.</p> <p>Methods</p> <p>Consecutive MTV riders and pillions, whether alive or dead, injured in a road traffic crash presenting to the emergency departments of two government hospitals and three branches of a private hospital in urban Hyderabad, India, were recruited to this study.</p> <p>Results</p> <p>378 MTV users were enrolled to the study of whom 333 (88.1%) were male, 252 (66.7%) were riders and median age was 31.3 years. A total of 223 (59%) MTV users were injured in multi-vehicle crashes while one-third had a frontal impact. The majority (77%) were assessed as having a Glasgow coma score (GCS) of 13–15, 12% a GCS of 9–12 and 11% a GCS of 3–8. No difference was seen in the severity distribution of injuries based on GCS among riders and pillions. Open wounds and superficial injuries to the head (69.3%) and upper extremity (27%) and lower extremity (24%) were the most common injuries. 43 (11%) sustained an intracranial injury, including 12 (28%) with associated fracture of the bones of the head. There were few differences in types of injuries sustained by riders and pillions though riders had a significantly lower risk of crush injuries of the lower extremity than pillions (relative risk, RR 0.25, 95% CI 0.08–0.81) and female pillions were at a significantly lower risk of sustaining fractures of the lower extremity than male pillions (RR 0.30, 95% CI 0.09 – 0.94). Overall, 42 (11%) MTV users died, of which 42.8% died before reaching the hospital. Only 74 (19.6%) MTV users had worn a helmet correctly and failure to wear a helmet was associated with a five times greater risk of intracranial injury (RR 4.99, 95% CI 1.23–20.1). Of the 19 pre-hospital deaths, 16 (84%) had not worn a helmet.</p> <p>Conclusion</p> <p>Head injuries accounted for the major proportion of injuries sustained in MTV users. Non-helmet use was associated with increased risk of serious head injuries. The data presented on the nature and severity of injuries sustained by MTV users can assist with planning to deal with these consequences as well as prevention of these injuries given the high use of MTV in India.</p

    Injury in China: a systematic review of injury surveillance studies conducted in Chinese hospital emergency departments

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    <p>Abstract</p> <p>Background</p> <p>Injuries represent a significant and growing public health concern in China. This <it>Review </it>was conducted to document the characteristics of injured patients presenting to the emergency department of Chinese hospitals and to assess of the nature of information collected and reported in published surveillance studies.</p> <p>Methods</p> <p>A systematic search of MEDLINE and China Academic Journals supplemented with a hand search of journals was performed. Studies published in the period 1997 to 2007 were included and research published in Chinese was the focus. Search terms included emergency, injury, medical care.</p> <p>Results</p> <p>Of the 268 studies identified, 13 were injury surveillance studies set in the emergency department. Nine were collaborative studies of which eight were prospective studies. Of the five single centre studies only one was of a prospective design. Transport, falls and industrial injuries were common mechanisms of injury. Study strengths were large patient sample sizes and for the collaborative studies a large number of participating hospitals. There was however limited use of internationally recognised injury classification and severity coding indices.</p> <p>Conclusion</p> <p>Despite the limited number of studies identified, the scope of each highlights the willingness and the capacity to conduct surveillance studies in the emergency department. This <it>Review </it>highlights the need for the adoption of standardized injury coding indices in the collection and reporting of patient health data. While high level injury surveillance systems focus on population-based priority setting, this <it>Review </it>demonstrates the need to establish an internationally comparable trauma registry that would permit monitoring of the trauma system and would by extension facilitate the optimal care of the injured patient through the development of informed quality assurance programs and the implementation of evidence-based health policy.</p

    Endoplasmic Reticulum Remodeling Tunes IP3-Dependent Ca2+ Release Sensitivity

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    The activation of vertebrate development at fertilization relies on IP3-dependent Ca2+ release, a pathway that is sensitized during oocyte maturation. This sensitization has been shown to correlate with the remodeling of the endoplasmic reticulum into large ER patches, however the mechanisms involved are not clear. Here we show that IP3 receptors within ER patches have a higher sensitivity to IP3 than those in the neighboring reticular ER. The lateral diffusion rate of IP3 receptors in both ER domains is similar, and ER patches dynamically fuse with reticular ER, arguing that IP3 receptors exchange freely between the two ER compartments. These results suggest that increasing the density of IP3 receptors through ER remodeling is sufficient to sensitize IP3-dependent Ca2+ release. Mathematical modeling supports this concept of ‘geometric sensitization’ of IP3 receptors as a population, and argues that it depends on enhanced Ca2+-dependent cooperativity at sub-threshold IP3 concentrations. This represents a novel mechanism of tuning the sensitivity of IP3 receptors through ER remodeling during meiosis
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