First aid treatment of burn injuries

The recommendations for the first aid treatment of burn injuries have previously been based upon conflicting published studies and as a result the recommendations have been vague with respect to optimal first aid treatment modality, temperature, duration and delay after which treatment is still effective. The public have also continued to use treatments such as ice and alternative therapies, however there is little evidence to support their use. Recently there have been several studies conducted by burn researchers in Australia which have enabled the recommendations to be clarified. First aid should consist of cool running water (2-15°C), applied for 20 minutes duration, as soon as possible but for up to 3 hours after the burn injury has occurred. Ice should not be used and alternative therapies should only be used to relieve pain as an adjunct to cold water treatment. Optimal first aid treatment significantly reduces tissue damage, hastens wound re-epithelialisation and reduces scarring and should be promoted widely to the public.

Cisplatin treatment of primary and metastatic epithelial ovarian carcinomas generates residual cells with mesenchymal stem cell-like profile

Epithelial mesenchymal transition (EMT) and cancer stem cells (CSC) have been associated with resistance to chemotherapy. Eighty percent of ovarian cancer patients initially respond to platinum-based combination therapy but most return with recurrence and ultimate demise. To better understand such chemoresistance we have assessed the potential role of EMT in tumor cells collected from advanced-stage ovarian cancer patients and the ovarian cancer cell line OVCA 433 in response to cisplatin in vitro. We demonstrate that cisplatin-induced transition from epithelial to mesenchymal morphology in residual cancer cells correlated with reduced E-cadherin, and increased N-cadherin and vimentin expression. The mRNA expression of Snail, Slug, Twist, and MMP-2 were significantly enhanced in response to cisplatin and correlated with increased migration. This coincided with increased cell surface expression of CSC-like markers such as CD44, α2 integrin subunit, CD117, CD133, EpCAM, and the expression of stem cell factors Nanog and Oct-4. EMT and CSC-like changes in response to cisplatin correlated with enhanced activation of extracellular signal-regulated kinase (ERK)1/2. The selective MEK inhibitor U0126 inhibited ERK2 activation and partially suppressed cisplatin-induced EMT and CSC markers. In vivo xenotransplantation of cisplatin-treated OVCA 433 cells in zebrafish embryos demonstrated significantly enhanced migration of cells compared to control untreated cells. U0126 inhibited cisplatin-induced migration of cells in vivo, suggesting that ERK2 signaling is critical to cisplatin-induced EMT and CSC phenotypes, and that targeting ERK2 in the presence of cisplatin may reduce the burden of residual tumor, the ultimate cause of recurrence in ovarian cancer patients.

Behaviour of natural zeolites used for the treatment of simulated and actual coal seam gas water

Coal seam gas operations produce significant quantities of associated water which often require demineralization. Ion exchange with natural zeolites has been proposed as a possible approach. The interaction of natural zeolites with solutions of sodium chloride and sodium bicarbonate in addition to coal seam gas water is not clear. Hence, we investigated ion exchange kinetics, equilibrium, and column behaviour of an Australian natural zeolite. Kinetic tests suggested that the pseudo first order equation best simulated the data. Intraparticle diffusion was part of the rate limiting step and more than one diffusion process controlled the overall rate of sodium ion uptake. Using a constant mass of zeolite and variable concentration of either sodium chloride or sodium bicarbonate resulted in a convex isotherm which was fitted by a Langmuir model. However, using a variable mass of zeolite and constant concentration of sodium ions revealed that the exchange of sodium ions with the zeolite surface sites was in fact unfavourable. Sodium ion exchange from bicarbonate solutions (10.3 g Na/kg zeolite) was preferred relative to exchange from sodium chloride solutions (6.4 g Na/kg zeolite). The formation of calcium carbonate species was proposed to explain the observed behaviour. Column studies of coal seam gas water showed that natural zeolite had limited ability to reduce the concentration of sodium ions (loading 2.1 g Na/kg zeolite) with rapid breakthrough observed. It was concluded that natural zeolites may not be suitable for the removal of cations from coal seam gas water without improvement of their physical properties.

Promising results with exemestane in the first-line treatment of metastatic breast cancer: a randomized phase II EORTC trial with a tamoxifen control.

Because tamoxifen (TAM), a nonsteroidal antiestrogen, is routinely used in the adjuvant setting, other hormone therapies are needed as alternatives for first-line treatment of metastatic breast cancer (MBC). Currently, exemestane (EXE) and other antiaromatase agents are indicated for use in patients who experience failure of TAM. In this multicenter, randomized, open-label, TAM-controlled (20 mg/day), phase II trial, we examined the activity and tolerability of EXE 25 mg/day for the first-line treatment of MBC in postmenopausal women. Exemestane was well tolerated and demonstrated substantial first-line antitumor activity based on intent-to-treat analysis of peer-reviewed responses. In the EXE arm, values for complete, partial, and objective response, clinical benefit, and time to tumor progression (TTP) exceeded those reported for TAM although no statistical comparison was made. Based on these encouraging results, a phase III trial will compare EXE and TAM.

Intermittent chemotherapy plus either intermittent or continuous cetuximab for first-line treatment of patients with KRAS wild-type advanced colorectal cancer (COIN-B): a randomised phase 2 trial

Background: Advanced colorectal cancer is treated with a combination of cytotoxic drugs and targeted treatments. However, how best to minimise the time spent taking cytotoxic drugs and whether molecular selection can refine this further is unknown. The primary aim of this study was to establish how cetuximab might be safely and effectively added to intermittent chemotherapy.

Methods: COIN-B was an open-label, multicentre, randomised, exploratory phase 2 trial done at 30 hospitals in the UK and one in Cyprus. We enrolled patients with advanced colorectal cancer who had received no previous chemotherapy for metastases. Randomisation was done centrally (by telephone) by the Medical Research Council Clinical Trials Unit using minimisation with a random element. Treatment allocation was not masked. Patients were assigned (1:1) to intermittent chemotherapy plus intermittent cetuximab or to intermittent chemotherapy plus continuous cetuximab. Chemotherapy was FOLFOX (folinic acid and oxaliplatin followed by bolus and infused fluorouracil). Patients in both groups received FOLFOX and weekly cetuximab for 12 weeks, then either had a planned interruption (those taking intermittent cetuximab) or planned maintenance by continuing on weekly cetuximab (continuous cetuximab). On RECIST progression, FOLFOX plus cetuximab or FOLFOX was recommenced for 12 weeks followed by further interruption or maintenance cetuximab, respectively. The primary outcome was failure-free survival at 10 months. The primary analysis population consisted of patients who completed 12 weeks of treatment without progression, death, or leaving the trial. We tested BRAF and NRAS status retrospectively. The trial was registered, ISRCTN38375681.

Findings: We registered 401 patients, 226 of whom were enrolled. Results for 169 with KRAS wild-type are reported here, 78 (46%) assigned to intermittent cetuximab and 91 (54%) to continuous cetuximab. 64 patients assigned to intermittent cetuximab and 66 of those assigned to continuous cetuximab were included in the primary analysis. 10-month failure-free survival was 50% (lower bound of 95% CI 39) in the intermittent group versus 52% (lower bound of 95% CI 41) in the continuous group; median failure-free survival was 12·2 months (95% CI 8·8–15·6) and 14·3 months (10·7–20·4), respectively. The most common grade 3–4 adverse events were skin rash (21 [27%] of 77 patients vs 20 [22%] of 92 patients), neutropenia (22 [29%] vs 30 [33%]), diarrhoea (14 [18%] vs 23 [25%]), and lethargy (20 [26%] vs 19 [21%]).

Interpretation: Cetuximab was safely incorporated in two first-line intermittent chemotherapy strategies. Maintenance of biological monotherapy, with less cytotoxic chemotherapy within the first 6 months, in molecularly selected patients is promising and should be validated in phase 3 trials.

Selecting the best targeted agent in first-line treatment of unresectable liver metastases from colorectal cancer:does the bench have the answers?

For physicians facing patients with organ-limited metastases from colorectal cancer, tumor shrinkage and sterilization of micrometastatic disease is the main goal, giving the opportunity for secondary surgical resection. At the same time, for the majority of patients who will not achieve a sufficient tumor response, disease control remains the predominant objective. Since FOLFOX or FOLFIRI have similar efficacies, the challenge is to define which could be the most effective targeted agent (anti-EGFR or anti-VEGF) to reach these goals. Therefore, a priori molecular identification of patients that could benefit from anti-EGFR or anti-VEGF monoclonal antibodies (i.e. the currently approved targeted therapies for metastatic colorectal cancer) is of critical importance. In this setting, the KRAS mutation status was the first identified predictive marker of response to anti-EGFR therapy. Since it has been demonstrated that tumors with KRAS mutation do not respond to anti-EGFR therapy, KRAS status must be determined prior to treatment. Thus, for KRAS wild-type patients, the choices that remain are either anti-VEGF or anti-EGFR. In this review, we present the most updated data from translational research programs dealing with the identification of biomarkers for response to targeted therapies.

The zooarchaeology of medieval Christendom: ideology, the treatment of animals and the making of medieval Europe

The formation of Christendom – of Europe – was associated with a standardized worldview expressing dominion over the natural world. While some sections of medieval society, specifically monasteries and the aristocratic class, appear to have developed this paradigm, there is also evidence for heterogeneity in practice and belief. Zooarchaeologists have accumulated vast quantities of data from medieval contexts which has enabled the ecological signatures of specific social groups to be identified, and how these developed from the latter centuries of the first millennium ad. It is possible from this to consider whether trends in animal exploitation can be associated with the Christian world view of dominion, and with the very idea of what it meant to be Christian. This may enable zooarchaeologists to situate the ecological trends of the Middle Ages within the context of Europeanization, and the consolidation of a Christian society.

Prevention and treatment of infant and childhood vitamin D deficiency in Australia and New Zealand : a consensus statement

• Vitamin D deficiency has re-emerged as a significant paediatric health issue, with complications including hypocalcaemic seizures, rickets, limb pain and fracture.

• A major risk factor for infants is maternal vitamin D deficiency. For older infants and children, risk factors include dark skin colour, cultural practices, prolonged breastfeeding, restricted sun exposure and certain medical conditions.

• To prevent vitamin D deficiency in infants, pregnant women, especially those who are dark-skinned or veiled, should be screened and treated for vitamin D deficiency, and breastfed infants of dark-skinned or veiled women should be supplemented with vitamin D for the first 12 months of life.

• Regular sunlight exposure can prevent vitamin D deficiency, but the safe exposure time for children is unknown.

• To prevent vitamin D deficiency, at-risk children should receive 400 IU vitamin D daily; if compliance is poor, an annual dose of 150 000 IU may be considered.

• Treatment of vitamin D deficiency involves giving ergocalciferol or cholecalciferol for 3 months (1000 IU/day if < 1 month of age; 3000 IU/ day if 1-12 months of age; 5000 IU/day if > 12 months of age).

• High-dose bolus therapy (300 000-500 000 IU) should be considered for children over 12 months of age if compliance or absorption issues are suspected.

World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Schizophrenia, Part 1: Update 2012 on the acute treatment of schizophrenia and the management of treatment resistance

These updated guidelines are based on a first edition of the World Federation of Societies of Biological Psychiatry Guidelines for Biological Treatment of Schizophrenia published in 2005. For this 2012 revision, all available publications pertaining to the biological treatment of schizophrenia were reviewed systematically to allow for an evidence-based update. These guidelines provide evidence-based practice recommendations that are clinically and scientifically meaningful and these guidelines are intended to be used by all physicians diagnosing and treating people suffering from schizophrenia. Based on the first version of these guidelines, a systematic review of the MEDLINE/PUBMED database and the Cochrane Library, in addition to data extraction from national treatment guidelines, has been performed for this update. The identified literature was evaluated with respect to the strength of evidence for its efficacy and then categorised into six levels of evidence (A-F; Bandelow et al. 2008b, World J Biol Psychiatry 9: 242). This first part of the updated guidelines covers the general descriptions of antipsychotics and their side effects, the biological treatment of acute schizophrenia and the management of treatment-resistant schizophrenia.

A randomized placebo-controlled trial of oxybutynin for the initial treatment of palmar and axillary hyperhidrosis

Introduction: Video-assisted thoracic sympathectomy provides excellent resolution of palmar and axillary hyperhidrosis but is associated with compensatory hyperhidrosis. Low doses of oxybutynin, an anticholinergic medication that competitively antagonizes the muscarinic acetylcholine receptor, can be used to treat palmar hyperhidrosis with fewer side effects. Objective: This study evaluated the effectiveness and patient satisfaction of oral oxybutynin at low doses (5 mg twice daily) compared with placebo for treating palmar hyperhidrosis. Methods: This was prospective, randomized, and controlled study. From December 2010 to February 2011, 50 consecutive patients with palmar hyperhidrosis were treated with oxybutynin or placebo. Data were collected from 50 patients, but 5 (10.0%) were lost to follow-up. During the first week, patients received 2.5 mg of oxybutynin once daily in the evening. From days 8 to 21, they received 2.5 mg twice daily, and from day 22 to the end of week 6, they received 5 mg twice daily. All patients underwent two evaluations, before and after (6 weeks) the oxybutynin treatment, using a clinical questionnaire and a clinical protocol for quality of life. Results: Palmar and axillary hyperhidrosis improved in >70% of the patients, and 47.8% of those presented great improvement. Plantar hyperhidrosis improved in >90% of the patients. Most patients (65.2%) showed improvements in their quality of life. The side effects were minor, with dry mouth being the most frequent (47.8%). Conclusions: Treatment of palmar and axillary hyperhidrosis with oxybutynin is a good initial alternative for treatment given that it presents good results and improves quality of life. (J Vasc Surg 2012;55:1696-700.)

Adding cetuximab to capecitabine plus oxaliplatin (XELOX) in first-line treatment of metastatic colorectal cancer: a randomized phase II trial of the Swiss Group for Clinical Cancer Research SAKK

BACKGROUND: To determine the activity and tolerability of adding cetuximab to the oxaliplatin and capecitabine (XELOX) combination in first-line treatment of metastatic colorectal cancer (MCC). PATIENTS AND METHODS: In a multicenter two-arm phase II trial, patients were randomized to receive oxaliplatin 130 mg/m(2) on day 1 and capecitabine 1000 mg/m(2) twice daily on days 1-14 every 3 weeks alone or in combination with standard dose cetuximab. Treatment was limited to a maximum of six cycles. RESULTS: Seventy-four patients with good performance status entered the trial. Objective partial response rates after external review and radiological confirmation were 14% and 41% in the XELOX and in the XELOX + Cetuximab arm, respectively. Stable disease has been observed in 62% and 35% of the patients, with 76% disease control in both arms. Cetuximab led to skin rash in 65% of the patients. The median overall survival was 16.5 months for arm A and 20.5 months for arm B. The median time to progression was 5.8 months for arm A and 7.2 months for arm B. CONCLUSION: Differences in response rates between the treatment arms indicate that cetuximab may improve outcome with XELOX. The correct place of the cetuximab, oxaliplatin and fluoropyrimidine combinations in first-line treatment of MCC has to be assessed in phase III trials.

Isotopic and chemical compositions of rocks and minerals from the TAG hydrothermal mound, ODP Site 957

Strontium- and oxygen-isotopic measurements of samples recovered from the Trans-Atlantic Geotraverse (TAG) hydrothermal mound during Leg 158 of the Ocean Drilling Program provide important constraints on the nature of fluid-rock interactions during basalt alteration and mineralization within an active hydrothermal deposit. Fresh Mid-Ocean Ridge Basalt (MORB), with a 87Sr/86Sr of 0.7026, from the basement beneath the TAG mound was altered at both low and high temperatures by seawater and altered at high temperature by near end-member black smoker fluids. Pillow breccias occurring beneath the margins of the mound are locally recrystallized to chlorite by interaction with large volumes of conductively heated seawater (>200°C). The development of a silicified, sulfide-mineralized stockwork within the basaltic basement follows a simple paragenetic sequence of chloritization followed by mineralization and the development of a quartz+pyrite+paragonite stockwork cut by quartz-pyrite veins. Initial alteration involved the development of chloritic alteration halos around basalt clasts by reaction with a Mg-bearing mixture of upwelling, high-temperature (>300°C), black smoker-type fluid with a minor (<10%) proportion of seawater. Continued high-temperature (>300°C) interaction between the wallrock and these Mg-bearing fluids results in the complete recrystallization of the wallrock to chlorite+quartz+pyrite. The quartz+pyrite+paragonite assemblage replaces the chloritized basalts, and developed by reaction at 250-360°C with end-member hydrothermal fluids having 87Sr/86Sr ~0.7038, similar to present-day vent fluids. The uniformity of the 87Sr/86Sr ratios of hydrothermal assemblages throughout the mound and stockwork requires that the 87Sr/86Sr ratio of end-member hydrothermal fluids has remained relatively constant for a time period longer than that required to change the interior thermal structure and plumbing network of the mound and underlying stockwork. Precipitation of anhydrite in breccias and as late-stage veins throughout most of the mound and stockwork, down to at least 125 mbsf, records extensive entrainment of seawater into the hydrothermal deposit. 87Sr/86Sr ratios indicate that most of the anhydrite formed from ~2:1 mixture of seawater and black smoker fluids (65%±15% seawater). Oxygen-isotopic compositions imply that anhydrite precipitated at temperatures between 147°C and 270°C and require that seawater was conductively heated to between 100°C and 180°C before mixing and precipitation occurred. Anhydrite from the TAG mound has a Sr-Ca partition coefficient Kd ~0.60±0.28 (2 sigma). This value is in agreement with the range of experimentally determined partition coefficients (Kd ~0.27-0.73) and is similar to those calculated for anhydrite from active black smoker chimneys from 21°N on the East Pacific Rise. The d18O (for SO4) of TAG anhydrite brackets the value of seawater sulfate oxygen (~9.5?). Dissolution of anhydrite back into the oceans during episodes of hydrothermal quiescence provides a mechanism of buffering seawater sulfate oxygen to an isotopically light composition, in addition to the precipitation and dissolution of anhydrite within the oceanic basement during hydrothermal recharge at the mid-ocean ridges.

Composition of rocks and minerals from the transition zone of the Reykjanes Ridge

Investigations of petrography, mineralogy, and chemical composition of gases and fluids in tuffs and lavas were carried out on samples dredged in the transition zone from the shelf and slope of Iceland to the Reykjanes Ridge. The samples were collected from the depths of 950-720 m during different expeditions of R/V Akademik Kurchatov and Mikhail Lomonosov. Mantle ultrabasite inclusions were first recognized in the region of Iceland. It can be assumed that they are related to eruptive structures formed on the ocean floor during Pliocene and are associated with the Iceland hot spot.

Composition and age of ores and bottom sediments accumulated within and near the Rainbow hydrothermal field

Results of direct geological and geochemical observations of the modern Rainbow hydrothermal field (Mid-Atlantic Ridge, 36°14'N; 33°54'W) carried out from the deep-sea manned Mir submersibles during Cruises 41 and 42 of the R/V Akademik Mstislav Keldysh in 1998-1999 and data of laboratory studies of collected samples are under consideration in the paper. The field lacks neovolcanic rocks and the axial part of the rift is filled in with a serpentinite protrusion. In this field there occur metalliferous sediments, as well as active and relict sulfide edifices composed of sulfide minerals; pyrrhotite, chalcopyrite, isocubanite, sphalerite, marcasite, pyrite, bornite, chalcosine, digenite, magnetite, anhydrite, rare troilite, wurtzite, millerite, and pentlandite have been determined. Sulfide ores are characterized by concentric-zoned textures. During in situ measurements during 35 minutes temperature of hydrothermal fluids was varying within a range from 250 to 350°C. Calculated chemical and isotopic composition of hydrothermal fluid shows elevated concentrations of Cl, Ni, Co, CH4, and H2. Values of d34S of H2S range from +2.4 to +3.1 per mil, of d13C of CH4 from -15.2 to -11.2 per mil, and d13C of CO2 from +1.0 to -4.0 per mil. Fluid inclusions are homogenized at temperatures from 140 to 360°C, whereas salinity of the fluid varies from 4.2 to 8.5 wt %. d34S values of sulfides range from +1.3 to +12.5 per mil. 3He/4He ratio in mineral-forming fluid contained in the fluid inclusions from sulfides of the Rainbow field varies from 0.00000374 to 0.0000101. It is shown that hydrothermal activity in the area continues approximately during 100 ka. It is assumed that the fluid and sulfide edifices contain components from the upper mantle. A hypothesis of phase separation of a supercritical fluid that results in formation of brines is proposed. Hydrothermal activity is related to the tectonic, not volcanic, phase of the Mid-Atlantic Ridge evolution.

Biosystematics of the first-stage larvae of some North American Bruchidae (Coleoptera) /

Includes appendix.