Although no pharmacological treatment has proved to be highly effective for reducing cocaine dependence, several medications have been tested over the last decade and have shown promising efficacy. Modafinil (Provigil), known as a treatment for day time sleepiness, and Topiramate (Topamax), an anti-epileptic medication also prescribed for migraine, have been shown to be effective in controlled clinical trials. We have recently started a major study utilizing Positron Emission Tomography (PET) brain imaging to monitor the progress of pharmacotherapy with modafinil or topiramate in cocaine-dependent and methadone-maintained cocaine-dependent patients. Patients will be assessed before treatment, and again after 4 weeks of pharmacotherapy. The aims of the project are to study effects of the two medications on cocaine dependence and craving, and on dopamine binding in the brain. At each assessment session, patients will undergo PET with [11C] raclopride to image the dopamine receptor DRD2. To trigger craving, patients will then be exposed to a videotape showing cocaine use; a questionnaire will be used to record their subjective responses, and a second PET scan will be performed with [18F] fluorodeoxyglucose (FDG) to image cerebral glucose metabolism during craving. This protocol was designed to enable us to study changes resulting from pharmacotherapy on dopamine binding in the brain, and on craving as reflected both in subjective measures and regional cerebral glucose metabolism. In addition, we will investigate the association between subjective measures of craving for cocaine and the level of dopamine DRD2 receptor occupancy in the brain before and after treatment. Notwithstanding the complexity of the clinical and therapeutic reality characterizing cocaine dependence, we hope to present preliminary evidence for the relative efficacy of these two promising medications in treatment for cocaine. dependence. This evidence could also elucidate the brain mechanisms underlying cocaine craving and dependence in cocaine-dependent patients.

Introduction: Oxygen is commonly administered to prehospital patients presenting with acute myocardial infarction (AMI). We conducted a systematic review to determine if oxygen administration, in AMI, impacts patient outcomes. Methods: We conducted a systematic search using MeSH terms and keywords in Medline, Embase, Cochrane Database of Systematic Reviews, Cochrane Central, clinicaltrials.gov and ISRCTN for relevant randomized controlled trials and observational studies comparing oxygen administration and no oxygen administration. The outcomes of interest were: mortality (≤30 days, in-hospital, and intermediate 2-11 months), infarct size, and major adverse cardiac events (MACE). Risk of Bias assessments were performed and GRADE methodology was employed to assess quality and overall confidence in the effect estimate. A meta-analysis was performed using RevMan 5 software. Results: Our search yielded 1192 citations of which 48 studies were reviewed as full texts and a total of 8 studies were included in the analysis. All evidence was considered low or very low quality. Five studies reported on mortality finding low quality evidence of no benefit or harm. Low quality evidence demonstrated no benefit or harm from supplemental oxygen administration. Similarly, no benefit or harm was found in MACE or infarct size (very low quality). Normoxia was defined as oxygen saturation measured via pulse oximetry at ≥90% in one recent study and ≥94% in another. Conclusion: We found low and very low quality evidence that the administration of supplemental oxygen to normoxic patients experiencing AMI, provides no clear harm nor benefit for mortality or MACE. The evidence on infarct size was inconsistent and warrants further prospective examination.

Introduction: Opioids are routinely administered for analgesia to prehospital patients experiencing chest discomfort from acute myocardial infarction (AMI). We conducted a systematic review to determine if opioid administration impacts patient outcomes. Methods: We conducted a systematic search using MeSH terms and keywords in Medline, Embase, Cochrane Database of Systematic Reviews, Cochrane Central and Clinicaltrials.gov for relevant randomized controlled trials and observational studies comparing opioid administration in AMI patients from 1990 to 2017. The outcomes of interest were: all-cause short-term mortality (≤30 days), major adverse cardiac events (MACE), platelet activity and aggregation, immediate adverse events, infarct size, and analgesia. Included studies were hand searched for additional citations. Risk of Bias assessments were performed and GRADE methodology was employed to assess quality and overall confidence in the effect estimate. Results: Our search yielded 3001 citations of which 19 studies were reviewed as full texts and a total of 9 studies were included in the analysis. The studies predominantly reported on morphine as the opioid. Five studies reported on mortality (≤30 days), seven on MACE, four on platelet activity and aggregation, two on immediate adverse events, two on infarct size and none on analgesic effect. We found low quality evidence suggesting no benefit or harm in terms of mortality or MACE. However, low quality evidence indicates that opioids increase infarct size. Low-quality evidence also shows reduced serum P2Y12 (eg: clopidogrel and ticagrelor) active metabolite levels and increased platelet reactivity in the first several hours post administration following an increase in vomiting. Conclusion: We find low and very low quality evidence that the administration of opioids in STEMI may be adversely related to vomiting and some surrogate outcomes including increased infarct size, reduced serum P2Y12 levels, and increased platelet activity. We found no clear benefit or harm on patient-oriented clinical outcomes including mortality.

We performed a spatial-temporal analysis to assess household risk factors for Ebola virus disease (Ebola) in a remote, severely-affected village. We defined a household as a family's shared living space and a case-household as a household with at least one resident who became a suspect, probable, or confirmed Ebola case from 1 August 2014 to 10 October 2014. We used Geographic Information System (GIS) software to calculate inter-household distances, performed space-time cluster analyses, and developed Generalized Estimating Equations (GEE). Village X consisted of 64 households; 42% of households became case-households over the observation period. Two significant space-time clusters occurred among households in the village; temporal effects outweighed spatial effects. GEE demonstrated that the odds of becoming a case-household increased by 4·0% for each additional person per household (P < 0·02) and 2·6% per day (P < 0·07). An increasing number of persons per household, and to a lesser extent, the passage of time after onset of the outbreak were risk factors for household Ebola acquisition, emphasizing the importance of prompt public health interventions that prioritize the most populated households. Using GIS with GEE can reveal complex spatial-temporal risk factors, which can inform prioritization of response activities in future outbreaks.

Field and greenhouse studies were conducted to evaluate selected PRE-applied herbicides for sprangletop control. In greenhouse studies, oxadiazon and dithiopyr provided excellent (> 89%) red sprangletop (L. filiformis) control. Pendimethalin and metolachlor + atrazine provided good (80–89%) to excellent control for 6 mo and 2 mo during studies 1 and 2, respectively. Isoxaben and atrazine provided poor (< 70%) control during both greenhouse studies. In field studies, good to excellent bearded sprangletop (L. fascicularis) control followed dithiopyr, pendimethalin, metolachlor, and metolachlor + atrazine treatments. Dithiopyr at 0.8 kg ai/ha provided best (> 95%) sprangletop control throughout the 6-mo testing period. Under field conditions, control was inconsistent following oxadiazon with good to excellent control during one study and poor control in another study. Better or equal control than metolachlor + atrazine followed dithiopyr, pendimethalin, and metolachlor alone treatments. Oxadiazon also provided similar or better control than metolachlor+atrazine in three of four studies. Over all studies, dithiopyr provided best sprangletop control, followed by metolachlor, metolachlor + atrazine, pendimethalin, and oxadiazon. Isoxaben and atrazine treatments provided poorest or inconsistent sprangletop control.

Pertussis epidemics have displayed substantial spatial heterogeneity in countries with high socioeconomic conditions and high vaccine coverage. This study aims to investigate the relationship between pertussis risk and socio-environmental factors on the spatio-temporal variation underlying pertussis infection. We obtained daily case numbers of pertussis notifications from Queensland Health, Australia by postal area, for the period January 2006 to December 2012. A Bayesian spatio-temporal model was used to quantify the relationship between monthly pertussis incidence and socio-environmental factors. The socio-environmental factors included monthly mean minimum temperature (MIT), monthly mean vapour pressure (VAP), Queensland school calendar pattern (SCP), and socioeconomic index for area (SEIFA). An increase in pertussis incidence was observed from 2006 to 2010 and a slight decrease from 2011 to 2012. Spatial analyses showed pertussis incidence across Queensland postal area to be low and more spatially homogeneous during 2006–2008; incidence was higher and more spatially heterogeneous after 2009. The results also showed that the average decrease in monthly pertussis incidence was 3·1% [95% credible interval (CrI) 1·3–4·8] for each 1 °C increase in monthly MIT, while average increase in monthly pertussis incidences were 6·2% (95% CrI 0·4–12·4) and 2% (95% CrI 1–3) for SCP periods and for each 10-unit increase in SEIFA, respectively. This study demonstrated that pertussis transmission is significantly associated with MIT, SEIFA, and SCP. Mapping derived from this work highlights the potential for future investigation and areas for focusing future control strategies.

We examined functional outcomes and quality of life of whole brain radiotherapy (WBRT) with integrated fractionated stereotactic radiotherapy boost (FSRT) for brain metastases treatment. Methods Eighty seven people with 1-3 brain metastases were enrolled on this Phase II trial of WBRT (30Gy/10)+simultaneous FSRT, (60Gy/10). Results Mean (Min-Max) baseline KPS, Mini Mental Status Exam (MMSE) and FACT-BR quality of life were 83 (70-100), 28 (21-30) and 143 (98-153). Lower baseline MMSE (but not KPS or FACT-Br) was associated with worse survival after adjusting for age, number of metastases, primary and extra-cranial disease status. Crude rates of deterioration (>10 points decrease from baseline for KPS and FACT-Br, MMSE fall to<27) ranged from 26-38% for KPS, 32-59% for FACT-Br and 0-16%for MMSE depending on the time-point assessed with higher rates generally noted at earlier time points (<6months post-treatment). Using a linear mixed models analysis, significant declines from baseline were noted for KPS and FACT-Br (largest effects at 6 weeks to 3 months) with no significant change in MMSE. Conclusions The effects on function and quality of life of this integrated treatment of WBRT+simultaneous FSRT were similar to other published series combining WBRT+SRS.

We report a longitudinal, prospective, multicentre cohort study designed to measure the outcomes of gastrostomy tube feeding in children with cerebral palsy (CP). Fifty-seven children with CP (28 females, 29 males; median age 4y 4mo, range 5mo to 17y 3mo) were assessed before gastrostomy placement, and at 6 and 12 months afterwards. Three-quarters of the children enrolled (43 of 57) had spastic quadriplegia; other diagnoses included mixed CP (6 of 57), hemiplegia (3 of 57), undiagnosed severe neurological impairment (3 of 57), ataxia (1 of 57), and extrapyramidal disorder (1 of 57). Only 7 of 57 (12%) could sit independently, and only 3 of 57 (5%) could walk unaided. Outcome measures included growth/anthropometry, nutritional intake, general health, and complications of gastrostomy feeding. At baseline, half of the children were more than 3SD below the average weight for their age and sex when compared with the standards for typically-developing children. Weight increased substantially over the study period; the median weight z score increased from –3 before gastrostomy placement to –2.2 at 6 months and –1.6 at 12 months. Almost all parents reported a significant improvement in their child's health after this intervention and a significant reduction in time spent feeding. Statistically significant and clinically important increases in weight gain and subcutaneous fat deposition were noted. Serious complications were rare, with no evidence of an increase in respiratory complications.

The aim of this prospective cohort study was to evaluate the impact of gastrostomy tube feeding on the quality of life of carers of children with cerebral palsy (CP). Short-Form 36 version II was used to measure quality of life in carers of 57 Caucasian children with CP (28 females, 29 males; median age 4y 4mo, range 5mo to 17y 3mo) six and 12 months after insertion of a gastrostomy tube. Responses were calibrated against a normative dataset (Oxford Healthy Life Survey III). Six months after gastrostomy feeding was started, a substantial rise in mean domain scores for mental health, role limitations due to emotional problems, physical functioning, social functioning, and energy/vitality were observed. At 12 months after gastrostomy placement, carers reported significant improvements in social functioning, mental health, energy/vitality (mean increase >9.8 points; p<0.03), and in general health perception (mean increase 6.35 points; p=0.045) compared with results at baseline. Moreover, the values obtained for these domains at 12 months were not significantly different from the normal reference standard. Carers reported a significant reduction in feeding times, increased ease of drug administration, and reduced concern about their child's nutritional status. This study has demonstrated a significant, measurable improvement in the quality of life of carers after insertion of a gastrostomy feeding tube.

Ištar of Nineveh at first glance presents a dilemma for the researcher. While she was a most important goddess, patron of a major town in north Mesopotamia, very little is known about her. As to her importance, in Hurrian religion Teššub and Ša'uška of Nineveh were heads of the pantheon. Here she is given her Hurrian name, Ša'uška. Thus the Mitanni king Tušratta in the Amarna letter no. 23, to Amenophis III, writes that Ša'uška of Nineveh, lady of all the lands (dMÙŠ šauruni-i-na nin kur-kur gáb-bi-i-ši-na-ma), wanted to travel to Egypt and to return. She is further called “lady of heaven” (nin ša-me-e) and “our lady” (nin-ne). Amarna letter no. 24, from the same Mitanni king to the same Pharaoh, refers to Ša'uška of Nineveh as “my goddess” (uruni-i-nu-a-a-we dša-uš-ka-a-wa de-en-ni-iw-wu-ú-a: VS XII 200 iii 98). One might conclude that “lady of heaven” alludes to her as Venus in the sky, but it might also mean the abode of the good gods without any astral allusion. It has been alleged that her wish to travel to Egypt was in the capacity of a goddess of healing, to cure the Pharaoh of his malady, but this is mere speculation. The letter gives no hint of this.

This brief international affair illustrates the problems excellently. There is a mass of cuneiform material bearing on the Sumerian Inanna and her Babylono-Assyrian counterpart Ištar, especially hymns and prayers. From them one can extract her major attributes — sexuality and war — and her astral presence in the planet Venus. The occurrence of related gods in other ancient Near Eastern regions — Aštart and Anat in Syria, Aṯtar in Arabia — suggests that the origins of the cult go back perhaps to neolithic time or even earlier, and the certain relationship with the Greek Aphrodite and Roman Venus attests to the power of this cult, however one explains the connection. However, in each Mesopotamian well-established centre of this cult one can assume that local customs and traditions will have added something to the basic “theology” we extract from our general knowledge of the goddess. For Ištar of Nineveh the episode of Tušratta may or may not allude to her star Venus, but otherwise it is totally uninformative about her “theology”. And that is typical for most of the other dated and precisely located evidence.

In the early 1980s a group of cuneiform tablets formerly in the collection of Sir Henry Wellcome housed at the Wellcome Historical Medical Museum arrived at the Birmingham City Museum and Art Gallery. The majority of these tablets were Ur III administrative texts that were published in Birmingham Cuneiform Tablets I–II. Other tablets in the collection included Old Akkadian, Old Babylonian and Late Babylonian documents, a Shulgi plaque, clay cones, inscribed bricks, a small group of astronomical texts, and a few unidentified miscellaneous tablets and fragments. One of these unidentified fragments turned out to be a hitherto unknown exemplar of Ludlul Bēl Nēmeqi Tablet I, and is the occasion of the current study.

An investigation was made during 1988 to test the hypothesis that ‘Grasslands Huia’ white clover (Trifolium repens L.) could be eliminated under close sheep grazing. The effects of grazing management, topography and fertilizer on the contribution of Huia plants to the white clover population in an 85 ha experimental upland pasture ecosystem in the southern North Island, New Zealand (lat. 40° 20′ S, long. 175° 50′ E, 125–350 m altitude) were quantified 11 years after oversowing. Replicated sampling sites (108 in total) were located on nine combinations of slope and aspect within grazing management treatments comprising rotational grazing with cattle (RC), rotational grazing with sheep (RS) and continuous grazing with sheep (CS), with high and low fertilizer treatments in each case. White clover occurrence, leaf area, phosphoglucoisomerase-2 (PGI-2) allele frequencies and the proportion of Grasslands Huia plants in the white clover population were determined at each site. White clover frequency was lower on steeper slopes. Aspect, slope and grazing management affected area of individual clover leaves. The proportion of Huia plants in the white clover population averaged 54·9, 49·0 and 33·6% for RC, RS and CS, respectively (P < 0·039, 5 D.F.). Fertilizer and topography did not affect the proportion of Huia. It was concluded that although Huia did persist after 11 years of close sheep grazing, its contribution to the total white clover population was unsatisfactory in some cases, and use of better adapted cultivars is suggested.