Reservoir sedimentation and spatiotemporal land use changes in their watersheds: the case of two sub-catchments of the White Volta Basin.

Reservoir storage is compromised by sedimentation for which reason it has become an important matter in reservoir operation and management. While many studies have investigated sediment deposition rate in reservoirs, few have analyzed reservoir sedimentation from their catchment's land use change perspective. Based on bathymetric survey conducted on two reservoirs in the White Volta Basin in 2020 and analysis of four Landsat satellite imagery (1986, 1996, 2006, and 2020) within their watersheds, this study assessed the land cover change within the watersheds to draw inferences on the rate of sedimentation of the reservoirs located downstream of their catchments. The results revealed rapid sedimentation in the small-sized reservoir (Vea), with an annual sedimentation rate of 0.304% and a nominal sedimentation rate of 0.17% for the mid-sized reservoir (Tono). Furthermore, the savannah forest within the Vea catchment declined drastically from 29.4% (1985) to 9.9% (2020) influenced by the rapid expansion of farmlands from 18.7% to 47.9% within the same period, respectively. On the other hand, the savannah forest within the Tono catchment declined from 34.7% (1985) to 21.6% (2020) due to farmland expansion from 19.2% to 39% within the same period, respectively. The higher sedimentation rate observed in the small-sized reservoir was observed to be worsened by extensive tree cover removal in its catchment. Therefore, land cover characteristics within a watershed have a significant bearing on the rate of sedimentation in the reservoirs located downstream of their catchment. Hence, adopting a multi-sectorial approach to dealing with land use management is necessary to sustain reservoirs' storage.

Gender medicine and oncology: report and consensus of an ESMO workshop.

BACKGROUND: The importance of sex and gender as modulators of disease biology and treatment outcomes is well known in other disciplines of medicine, such as cardiology, but remains an undervalued issue in oncology. Considering the increasing evidence for their relevance, European Society for Medical Oncology decided to address this topic and organized a multidisciplinary workshop in Lausanne, Switzerland, on 30 November and 1 December 2018. DESIGN: Twenty invited faculty members and 40 selected physicians/scientists participated. Relevant content was presented by faculty members on the basis of a literature review conducted by each speaker. Following a moderated consensus session, the final consensus statements are reported here. RESULTS: Clinically relevant sex differences include tumour biology, immune system activity, body composition and drug disposition and effects. The main differences between male and female cells are sex chromosomes and the level of sexual hormones they are exposed to. They influence both local and systemic determinants of carcinogenesis. Their effect on carcinogenesis in non-reproductive organs is largely unknown. Recent evidence also suggests differences in tumour biology and molecular markers. Regarding body composition, the difference in metabolically active, fat-free body mass is one of the most prominent: in a man and a woman of equal weight and height, it accounts for 80% of the man's and 65% of the woman's body mass, and is not taken into account in body-surface area based dosing of chemotherapy. CONCLUSION: Sex differences in cancer biology and treatment deserve more attention and systematic investigation. Interventional clinical trials evaluating sex-specific dosing regimens are necessary to improve the balance between efficacy and toxicity for drugs with significant pharmacokinetic differences. Especially in diseases or disease subgroups with significant differences in epidemiology or outcomes, men and women with non-sex-related cancers should be considered as biologically distinct groups of patients, for whom specific treatment approaches merit consideration.

Crimean-Congo hemorrhagic fever virus in livestock ticks and animal handler seroprevalence at an abattoir in Ghana.

BACKGROUND: Crimean-Congo Haemorrhagic Fever Virus (CCHFV) is a zoonotic virus transmitted by Ixodid ticks and causes Crimean-Congo hemorrhagic fever (CCHF) disease in humans with up to 50 % mortality rate. METHODS: Freshly slaughtered livestock at the Kumasi abattoir in the Ashanti Region of Ghana were examined for the presence of ticks once a month over a 6-month period from May to November 2011. The ticks were grouped into pools by species, sex, and animal source. CCHFV was detected in the ticks using reverse transcription PCR. Blood samples were collected from enrolled abattoir workers at initiation, and from those who reported fever in a preceding 30-day period during monthly visits 2-5 months after initiation. Six months after initiation, all participants who provided baseline samples were invited to provide blood samples. Serology was performed using enzyme linked immunosorbent assay (ELISA). Demographic and epidemiological data was also obtained from enrolled participants using a structured questionnaire. RESULTS: Of 428 freshly slaughtered animals comprising 130 sheep, 149 cattle, and 149 goats examined, 144 ticks belonging to the genera Ambylomma, Hyalomma and Boophilus were identified from 57 (13.3 %): 52 (34.9 %), 4 (3.1 %) and 1 (0.7 %) cattle, sheep and goat respectively. Of 97 tick pools tested, 5 pools comprising 1 pool of Hyalomma excavatum and 4 pools of Ambylomma variegatum, collected from cattle, were positive for CCHFV. Of 188 human serum samples collected from 108 abattoir workers, 7 (3.7 %) samples from 6 persons were anti-CCHF IgG positive with one of them also being CCHF IgM positive. The seroprevalence of CCHFV identified in this study was 5.7 %. CONCLUSIONS: This study detected human exposure to CCHF virus in slaughterhouse workers and also identified the CCHF virus in proven vectors (ticks) of Crimean Congo hemorrhagic fever in Ghana. The CCHFV was detected only in ticks collected from cattle, one of the livestock known to play a role in the amplification of the CCHF virus.

Enhanced FGFR signalling predisposes pancreatic cancer to the effect of a potent FGFR inhibitor in preclinical models.

BACKGROUND: Fibroblast growth factor receptor (FGFR) signalling has been implicated in pancreas carcinogenesis. We investigated the effect of FGFR inhibition in pancreatic cancer in complementary cancer models derived from cell lines and patient-derived primary tumour explants. METHODS: The effects of FGFR signalling inhibition in pancreatic cancer were evaluated using anti-FRS2 shRNA and dovitinib. Pancreatic cancers with varying sensitivity to dovitinib were evaluated to determine potential predictive biomarkers of efficacy. Primary pancreatic explants with opposite extreme of biomarker expression were selected from 13 tumours for in vivo dovitinib treatment. RESULTS: Treatment with anti-FRS2 shRNA induced significant in vitro cell kill in pancreatic cancer cells. Dovitinib treatment achieved similar effects and was mediated by Akt/Mcl-1 signalling in sensitive cells. Dovitinib efficacy correlated with FRS2 phosphorylation status, FGFR2 mRNA level and FGFR2 IIIb expression but not phosphorylation status of VEGFR2 and PDGFRß. Using FGFR2 mRNA level, a proof-of-concept study using primary pancreatic cancer explants correctly identified the tumours' sensitivity to dovitinib. CONCLUSION: Inhibiting FGFR signalling using shRNA and dovitinib achieved significant anti-cancer cancer effects in pancreatic cancer. The effect was more pronounced in FGFR2 IIIb overexpressing pancreatic cancer that may be dependent on aberrant stimulation by stromal-derived FGF ligands.

A phase II multicentre study of ziv-aflibercept in combination with cisplatin and pemetrexed in patients with previously untreated advanced/metastatic non-squamous non-small cell lung cancer.

BACKGROUND: This study evaluated the efficacy and safety of ziv-aflibercept in combination with cisplatin and pemetrexed in non-small cell lung cancer (NSCLC). METHODS: This single arm, multicentre phase II trial enrolled patients with previously untreated, locally advanced or metastatic non-squamous NSCLC. Patients received intravenous ziv-aflibercept 6 mg kg(-1), pemetrexed 500 mg m(-2), and cisplatin 75 mg m(-2), every 21 days for up to six cycles. Maintenance administration of ziv-aflibercept was to continue until disease progression, intolerable toxicity or other cause for withdrawal. The co-primary end points were objective response rate (ORR) and progression-free survival (PFS). Planned sample size was 72 patients. RESULTS: The study was closed prematurely because of three confirmed and two suspected cases of reversible posterior leukoencephalopathy syndrome (RPLS). A total of 42 patients were enrolled. Median age was 61.5 years; 55% were male, 86% Caucasian and 50% had Eastern Cooperative Oncology Group performance status (ECOG PS)=0. A median of four cycles of ziv-aflibercept was administered. The most common treatment-emergent adverse events (TEAEs) of any grade were nausea (69%) and fatigue (67%), with hypertension (36%) as the most common grade 3/4 TEAE. Of the 38 evaluable patients, ORR was 26% and median PFS was 5 months. CONCLUSION: Cases of RPLS had been observed in other studies in the ziv-aflibercept clinical development programme but the rate observed in this study was higher than previously observed. This might be related to declining renal function and/or hypertension. Although ORR and PFS were in accordance with most historical first-line NSCLC studies, this combination of ziv-aflibercept/cisplatin/pemetrexed will not be further explored in NSCLC.

2nd ESMO Consensus Conference on Lung Cancer: non-small-cell lung cancer first-line/second and further lines of treatment in advanced disease.

To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The 2nd ESMO Consensus Conference on Lung Cancer was held on 11-12 May 2013 in Lugano. A total of 35 experts met to address several questions on non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, first-line/second and further lines of treatment in advanced disease, early-stage disease and locally advanced disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on first line/second and further lines of treatment in advanced disease.

Elements of person-centred diagnostic imaging care in low-and middle-income countries: A systematic review.

INTRODUCTION: Diagnostic imaging professionals are trained to deliver safe and high-quality person-centred radiographic diagnostic imaging care. The term person-centred care has been described as a confused concept without a unified definition. This systematic review identified the elements that have been used to measure person-centred care in diagnostic imaging in low- and middle-income countries (LMICs). METHODS: A systematic review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. Embase, MEDLINE and Cochrane library were searched. Bias was assessed using the Critical Appraisal Skill Programme and Mixed Method Appraisal Tool. A narrative synthesis guided by the Picker Principles of person-centred care was undertaken. RESULTS: Of the 4482 articles identified, 26 articles were included. The studies were from 12 LMICs. Synthesis of the literature generated six themes, namely access to high quality and safe diagnostic imaging care, effective communication and shared diagnostic imaging decision making, suitable diagnostic imaging environment for physical comfort, respectful and compassionate diagnostic radiographers, effective coordination of diagnostic imaging care process, and family and friends' involvement in diagnostic imaging care. CONCLUSION: Medical imaging facilities in most LMICs continue to struggle with issues of access, safety, quality, and responsiveness to the needs of patients. The need for innovative person-centred diagnostic imaging care interventions in LMICs has become urgent. IMPLICATIONS FOR PRACTICE: If diagnostic imaging services in LMICs are to move beyond the current models of limited person-centred access to care, a greater focus on systems thinking is required. It is imperative to involve all stakeholders, not only patients and radiographers, but also policymakers whose works impact on equitable access to diagnostic imaging services.

Work-related back pain among diagnostic radiographers in Ghana: A qualitative study.

INTRODUCTION: Work-related back pain has a major impact on diagnostic radiographers' clinical task performance in terms of sickness absenteeism, disability and loss of productivity due to presenteeism. However, there is limited information about the burden of work-related back pain among diagnostic radiographers in Ghana. The aim was to explore diagnostic radiographers' experiences of work-related back pain in Ghana. METHODS: An exploratory-descriptive qualitative study using semi-structured telephone interviews was conducted. Purposive and snowball sampling techniques were used to recruit participants. The interviews were facilitated by an interview guide. Thematic network approach was used to analyse the data. RESULTS: Eighteen participants, with 14 males and 4 females were interviewed. The mean age of the participants was 31.7 ± 7.3 years. Three themes were developed: increasing burden of work-related back pain; making sense of the multifaceted risk factors for work-related back pain; and preventing work-related back pain. Low back pain was the most common, followed by neck pain with thoracic pain as the least common reported work-related back pain by participants. Identified risk factors included: physical factors; environmental ergonomic factors; and psychosocial factors. Prevention strategies identified were categorised into: health and safety training; creating lifting team; leadership support from diagnostic imaging managers; participatory ergonomics; workforce planning and scheduling; mindfulness exercises; and physical rehabilitation. CONCLUSION: Assessing the level of ergonomic risks is critical to identifying, analysing and controlling workplace risk factors that can lead to work-related back pain among diagnostic radiographers. Future research is recommended to design and evaluate a multicomponent ergonomic intervention for the prevention of work-related back pain among diagnostic radiographers to enable them deliver care safely and healthily. IMPLICATIONS FOR PRACTICE: Understanding diagnostic radiographers experiences of work-related back pain can help develop effective strategies to reduce the growing burden of pain back.

Groundwater quality and potential analysis using geospatial techniques: The case of Ashanti Region in Ghana.

The ecosystem and economy's reliance on clean water is influenced by various factors such as geology, topography, soil types, activities, and the presence of plants and animals. The Ghana Water Company is encountering difficulties in delivering water to consumers in the Ashanti Region due to the shortage of surface water resources, leading to water rationing in the area. Furthermore, poor waste disposal practices, illegal mining, use of fertilizers, and industrial activities have resulted in surface and groundwater source damage. Therefore, there is a need to implement a reliable, simple, and timely method to assess groundwater quality. This study aims to employ GIS and RS techniques to evaluate groundwater quality and potential in the Ashanti Region, Ghana. The Water Quality Index (WQI) was estimated using pH, Total Dissolve Solid (TDS), Chloride, Total Hardness (TH), Nitrate, Temperature, Turbidity, Iron, and Electrical Conductivity (EC). The study then used the WQI distribution to conduct a groundwater potential analysis to identify suitable areas for borehole placement. Digital thematic layers and maps were developed to expose the spatial distribution of water quality parameters, enabling the identification of groundwater pollution control and remedial measures. The study estimated the region's groundwater potential using an integrated GIS and Analytical Hierarchical Process (AHP) technique, grouping under excellent, good, fair, and poor potential. The WQI in the Ashanti Region ranged from 5.208 to 134.232, with 32.252% of the study area having an excellent WQI and 60.168% of the study area having a good WQI. Poor water quality covered 7.550% of the study area. The results showed that the GIS-based AHP approach accurately mapped the spatial distribution of WQI and Groundwater Potential Zones (GWPZ). This information is helpful to planners in water resource management in groundwater exploration and future planning. Policymakers and stakeholders must ensure that groundwater sources are protected from pollution.

A multicenter phase 1 study of PX-866 in combination with docetaxel in patients with advanced solid tumours.

BACKGROUND: This phase I, dose-finding study determined the safety, maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D), pharmacokinetics, and antitumour activity of PX-866, a phosphatidylinositol 3-kinase inhibitor, combined with docetaxel in patients with incurable solid tumours. METHODS: PX-866 was administered at escalating doses (4-8 mg daily) with docetaxel 75 mg m⁻² intravenously every 21 days. Archived tumour tissue was assessed for potential predictive biomarkers. RESULTS: Forty-three patients were enrolled. Most adverse events (AEs) were grade 1 or 2. The most frequent study drug-related AE was diarrhoea (76.7%), with gastrointestinal disorders occurring in 79.1% (docetaxel-related) and 83.7% (PX-866-related). No dose-limiting toxicities were observed. The RP2D was 8 mg, the same as the single-agent MTD. Co-administration of PX-866 and docetaxel did not affect either drug's PKs. Best responses in 35 evaluable patients were: 2 partial responses (6%), 22 stable disease (63%), and 11 disease progression (31%). Eleven patients remained on study for >180 days, including 8 who maintained disease control on single-agent PX-866. Overall median progression-free survival (PFS) was 73.5 days (range: 1-569). A non-significant association between longer PFS for PIK3CA-MUT/KRAS-WT vs PIK3CA-WT/KRAS-WT was observed. CONCLUSION: Treatment with PX-866 and docetaxel was well tolerated, without evidence of overlapping/cumulative toxicity. Further investigation with this combination is justified.

Challenges in oncology career: are we closing the gender gap? Results of the new ESMO Women for Oncology Committee survey.

BACKGROUND: Following a European Society for Medical Oncology Women for Oncology (ESMO W4O) survey in 2016 showing severe under-representation of female oncologists in leadership roles, ESMO launched a series of initiatives to address obstacles to gender equity. A follow-up survey in October 2021 investigated progress achieved. MATERIALS AND METHODS: The W4O questionnaire 2021 expanded on the 2016 survey, with additional questions on the impact of ethnicity, sexual orientation and religion on career development. Results were analysed according to respondent gender and age. RESULTS: The survey sample was larger than in 2016 (n = 1473 versus 482), especially among men. Significantly fewer respondents had managerial or leadership roles than in 2016 (31.8% versus 51.7%). Lack of leadership development for women and unconscious bias were considered more important in 2021 than in 2016. In 2021, more people reported harassment in the workplace than in 2016 (50.3% versus 41.0%). In 2021, ethnicity, sexual orientation and religion were considered to have little or no impact on professional career opportunities, salary setting or related potential pay gap. However, gender had a significant or major impact on career development (25.5% of respondents), especially in respondents ≤40 years of age and women. As in 2016, highest ranked initiatives to foster workplace equity were promotion of work-life balance, development and leadership training and flexible working. Significantly more 2021 respondents (mainly women) supported the need for culture and gender equity education at work than in 2016. CONCLUSIONS: Gender remains a major barrier to career progression in oncology and, although some obstacles may have been reduced since 2016, we are a long way from closing the gender gap. Increased reporting of discrimination and inappropriate behaviour in the workplace is a major, priority concern. The W4O 2021 survey findings provide new evidence and highlight the areas for future ESMO interventions to support equity and diversity in oncology career development.

Prophylactic cranial irradiation in small-cell lung cancer: findings from a North Central Cancer Treatment Group Pooled Analysis.

BACKGROUND: This pooled analysis evaluated the outcomes of prophylactic cranial irradiation (PCI) in 739 small-cell lung cancer (SCLC patients with stable disease (SD) or better following chemotherapy ± thoracic radiation therapy (TRT) to examine the potential advantage of PCI in a wider spectrum of patients than generally participate in PCI trials. PATIENTS AND METHODS: Three hundred eighteen patients with extensive SCLC (ESCLC) and 421 patients with limited SCLC (LSCLC) participated in four phase II or III trials. Four hundred fifty-nine patients received PCI (30 Gy/15 or 25 Gy/10) and 280 did not. Survival and adverse events (AEs) were compared. RESULTS: PCI patients survived significantly longer than non-PCI patients {hazard ratio [HR] = 0.61 [95% confidence interval (CI): 0.52-0.72]; P < 0.0001}. The 1- and 3-year survival rates were 56% and 18% for PCI patients versus 32% and 5% for non-PCI patients. PCI was still significant after adjusting for age, performance status, gender, stage, complete response, and number of metastatic sites (HR = 0.82, P = 0.04). PCI patients had significantly more grade 3+ AEs (64%) compared with non-PCI patients (50%) (P = 0.0004). AEs associated with PCI included alopecia and lethargy. Dose fractionation could be compared only for LSCLC patients and 25 Gy/10 was associated with significantly better survival compared with 30 Gy/15 (HR = 0.67, P = 0.018). CONCLUSIONS: PCI was associated with a significant survival benefit for both ESCLC and LSCLC patients who had SD or a better response to chemotherapy ± TRT. Dose fractionation appears important. PCI was associated with an increase in overall and specific grade 3+ AE rates.

Has COVID-19 had a greater impact on female than male oncologists? Results of the ESMO Women for Oncology (W4O) Survey.

BACKGROUND: European Society for Medical Oncology Women for Oncology (ESMO W4O) research has previously shown under-representation of female oncologists in leadership roles. As early reports suggested disproportionate effects of the COVID-19 pandemic on women, the ESMO W4O Committee initiated a study on the impact of the pandemic on the lives of female and male oncologists. METHODS: A questionnaire was sent to ESMO members and put on the ESMO website between 8 June 2020 and 2 July 2020. Questions focused on the working (hospital tasks, laboratory tasks, science) and home (household management, childcare, parent care, personal care) lives of oncologists during and after COVID-19-related lockdowns. RESULTS: Of 649 respondents, 541 completed the questionnaire. Of these, 58% reported that COVID-19 had affected their professional career, 83% of whom said this was in a negative way (85% of women versus 76% of men). Approximately 86% reported that COVID-19 had changed their personal life and 82% their family life. Women were again significantly more affected than men: personal life (89% versus 78%; P = 0.001); family life (84% versus 77%; P = 0.037). During lockdowns, women reported increased time spent on hospital and laboratory tasks compared with men (53% versus 46% and 33% versus 26%, respectively) and a significantly higher proportion of women than men spent less time on science (39% versus 25%) and personal care (58% versus 39%). After confinement, this trend remained for science (42% versus 23%) and personal care (55% versus 36%). CONCLUSIONS: The COVID-19 pandemic has adversely affected the professional and home lives of oncologists, especially women. Reduced research time for female oncologists may have long-lasting career consequences, especially for those at key stages in their career. The gender gap for promotion to leadership positions may widen further as a result of the pandemic.

Female leadership in oncology-has progress stalled? Data from the ESMO W4O authorship and monitoring studies.

BACKGROUND: Exploratory research showed that female oncologists are frequently under-represented in leadership roles. European Society for Medical Oncology (ESMO) Women for Oncology (W4O) therefore implemented gender equality programs in career development and established international studies on female representation at all stages of the oncology career pathway. METHODS: For 2017-2019, data were collected on (i) first and last authorship of publications in five major oncology journals and (ii) representation of women in leadership positions in oncology-as invited speakers at National/International congresses, board members or presidents of National/International societies and ESMO members. The 2015/2016 data from the first published W4O Study were incorporated for comparisons. RESULTS: Across 2017-2019, female oncologists were significantly more likely to be first than last authors (P < 0.001). The proportion of female first authors was similar across years: 38.0% in 2017, 37.1% in 2018, 41.0% in 2019 (P = 0.063). The proportion of female last authors decreased from 30.4% in 2017 to 24.2% in 2018 (P = 0.0018) and increased to 28.5% in 2019 (P = 0.018). Across 2015-2019, invited speakers at International/National oncology congresses were significantly less likely to be female than male (P < 0.001; 29.7% in 2015 to 36.8% in 2019). Across 2016-2019, board members of International/National oncology societies were significantly less likely to be female than male (P < 0.001; 26.8% in 2016 to 35.8% in 2019). There were statistically significant increasing trends in female speakers and board members across the study periods (P < 0.001 for both). Societies with a female president had a higher proportion of female board members across these periods (P = 0.026). CONCLUSIONS: Reported progress towards gender equality in career development in oncology is real but slow. Women in leadership positions are essential for encouraging young women to aspire to and work towards similar or greater success. Therefore, continued monitoring is needed to inform ESMO W4O initiatives to promote gender balance at all stages of the career pathway.

A phase II study of cetuximab and radiation in elderly and/or poor performance status patients with locally advanced non-small-cell lung cancer (N0422).

BACKGROUND: Non-small-cell lung cancer (NSCLC) is a disease of the elderly. Seeking a tolerable but effective regimen, we tested cetuximab + radiation in elderly and/or poor performance status patients with locally advanced NSCLC. PATIENTS AND METHODS: Older patients [≥ 65 years with an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2] or younger patients (performance status of 2) received cetuximab 400 mg/m(2) i.v. on day 1 followed by weekly cetuximab 250 mg/m(2) i.v. with concomitant radiation of 6000 cGy in 30 fractions. The primary end point was the percentage who lived 11+ months. RESULTS: This 57-patient cohort had a median age (range) of 77 years (60-87), and 12 (21%) had a performance status of 2. Forty of 57 (70%) lived 11+ months, thus exceeding the anticipated survival rate of 50%. The median survival was 15.1 months [95% confidence interval (CI) 13.1-19.3 months], and the median time to cancer progression was 7.2 months (95% CI 5.8-8.6 months). No treatment-related deaths occurred, but 31 patients experienced grade 3+ adverse events, most commonly fatigue, anorexia, dyspnea, rash, and dysphagia, each of which occurred in <10% of patients. CONCLUSION: This combination merits further study in this group of patients.

Predicting the safety of medicines in pregnancy: A workshop report.

The framework for developmental toxicity testing has remained largely unchanged for over 50 years and although it remains invaluable in assessing potential risks in pregnancy, knowledge gaps exist, and some outcomes do not necessarily correlate with clinical experience. Advances in omics, in silico approaches and alternative assays are providing opportunities to enhance our understanding of embryo-fetal development and the prediction of potential risks associated with the use of medicines in pregnancy. A workshop organised by the Medicines and Healthcare products Regulatory Agency (MHRA), "Predicting the Safety of Medicines in Pregnancy - a New Era?", was attended by delegates representing regulatory authorities, academia, industry, patients, funding bodies and software developers to consider how to improve the quality of and access to nonclinical developmental toxicity data and how to use this data to better predict the safety of medicines in human pregnancy. The workshop delegates concluded that based on comparative data to date alternative methodologies are currently no more predictive than conventional methods and not qualified for use in regulatory submissions. To advance the development and qualification of alternative methodologies, there is a requirement for better coordinated multidisciplinary cross-sector interactions coupled with data sharing. Furthermore, a better understanding of human developmental biology and the incorporation of this knowledge into the development of alternative methodologies is essential to enhance the prediction of adverse outcomes for human development. The output of the workshop was a series of recommendations aimed at supporting multidisciplinary efforts to develop and validate these alternative methodologies.

Hepatitis E virus infection among pig handlers in Accra, Ghana.

OBJECTIVE: To determine the correlates of hepatitis E virus infection (HEV) in a sample of persons who work with pigs. DESIGN: Cross-sectional study. SETTING: Three pig farms in the Greater Accra Region of Ghana. SUBJECTS: Persons who work with pigs seen at the selected pig farms between the months of January and May 2008. RESULTS: One hundred and five persons who work with pigs voluntarily completed a risk-factor questionnaire and provided blood samples for unlinked anonymous testing for the presence of antibodies to HEV. The median age of participants was 36.5 +/- 15.0 years (range 12-65 years). Of the 105 subjects tested, HEV seroprevelance was 38.1%. On multivariate analysis, the independent determinants of HEV infection were being employed on the farm for less than six months (odds ratio (OR) 9.1; 95% confidence interval (95% CI) 1.0-81.4 and having piped water in the household and/or on the farm (OR 3.9; 95% CI 0.4-90.8). CONCLUSION: Consistent with similar studies worldwide, the results of our studies revealed a high prevalence of HEV infection in persons who work with pigs. Further studies need to be done to isolate, characterise the virus and define the clinical and epidemiological significance of HEV infection in this population.

Clinical studies of pemetrexed and gemcitabine combinations.

Pemetrexed (ALIMTA) is a novel multitargeted antifolate that inhibits thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase. This agent is broadly active in a wide variety of solid tumors, including breast cancer, bladder cancer, mesothelioma, non-small-cell lung cancer, pancreatic cancer and ovarian cancer. Pemetrexed has also shown clinically relevant activity in combination with gemcitabine. This combination has been, and continues to be evaluated for the treatment of a number of malignancies, including non-small cell lung and ovarian cancer. A recently published randomized trial of different sequences has identified the sequence of pemetrexed on day 1 followed by gemcitabine on day 1 and gemcitabine on day 8, every 21 days as the most efficacious and least toxic sequence.