Predictive markers of endocrine response in breast cancer

Ongoing clinical and research efforts seek to optimise the use of endocrine therapy in the treatment of breast cancer. Accurate biomarkers are needed that predict response for individual patients. The presence of the estrogen receptor(ER) as the direct(for tamoxifen and fulvestrant) or indirect(for aromatase inhibitors) target molecule for endocrine therapy remains the foremost biomarker and determinant of response. However, ER expression only poorly predicts outcome and further indicators of response or resistance are required. The development and application of molecular signature assays such as Oncotype Dx, Prosigna, Mammaprint and Endopredict have provided valuable information on prognosis and these are being used to support clinical decision making on whether endocrine therapy alone alongside surgery is sufficient for ER-positive early stage breast cancers or whether combination of endocrine with chemotherapy are also warranted. Ki67, the proliferation marker, has been widely used in the neo-adjuvant(pre-operative) setting to help predict response and long term outcome. Gene expression studies within the same setting have allowed monitoring of changes of potential predictive markers. These have identified frequent changes in estrogenregulated and proliferation genes. Specific molecules such as mutant ER may also prove helpful biomarkers in predicting outcome and monitoring response to treatment.

Green manure rotation and application increase rice yield and soil carbon in the Yangtze River valley of China

The addition of organic matter via green manure rotation with rice is considered a smart agricultural practice to maintain soil productivity and support environmental sustainability.However,few studies have quantitatively assessed the impact of green manure rotation and application on the interactions between agronomic management practice,soil fertility,and crop production.In this study,800 pairs of data from 108 studies conducted in the agricultural region of the Yangtze River,China were assessed,and random forest(RF)modeling was performed to evaluate the effect of green manure rotation and application on rice yield and soil properties.Compared to a winter fallow system,rotation and application of green manure significantly increased rice yield and soil organic carbon(SOC)by 8.1%and 8.4%,respectively.According to the RF models,rice type,green manure application rate and duration,mineral and organic nitrogen application rates,and initial SOC content and soil pH were identified as the main drivers for rice yield and SOC changes.Marginal benefit analysis revealed that green manure application rates for early rice in double cropping system and the rice in single cropping system were approximately 20 and 26 t ha-1(fresh weight),respectively.Further,the optimum green manure application rate was approximately 25 t ha-1(fresh weight)for carbon sequestration.However,it should be noted that green manure application to soils with high SOC level might result in the soils becoming a net carbon source.Our study contributed scientific and quantitative indicators for achieving the greatest benefits in rice yield and increasing SOC upon application of green manure.

Estimating the economic and social consequences for patients diagnosed with human African trypanosomiasis in Muchinga,Lusaka and Eastern Provinces of Zambia(2004-2014)

Background:Acute human African trypanosomiasis(rHAT)caused by Trypanosoma brucei rhodesiense is associated with high mortality and is fatal if left untreated.Only a few studies have examined the psychological,social and economic impacts of rHAT.In this study,mixed qualitative and quantitative research methods were used to evaluate the socio-economic impacts of rHAT in Mambwe,Rufunsa,Mpika and Chama Districts of Zambia.Methods:Individuals diagnosed with rHAT from 2004 to 2014 were traced using hospital records and discussions with communities.Either they,or their families,were interviewed using a structured questionnaire and focus group discussions were conducted with affected communities.The burden of the disease was investigated using disability adjusted life years(DALYs),with and without discounting and age-weighting.The impact of long-term disabilities on the rHAT burden was also investigated.Results:Sixty four cases were identified in the study.The majority were identified in second stage,and the mortality rate was high(12.5%).The total number of DALYs was 285 without discounting or age-weighting.When long-term disabilities were included this estimate increased by 50%to 462.The proportion of years lived with disability(YLD)increased from 6.4%to 37%of the undiscounted and un-age-weighted DALY total.When a more active surveillance method was applied in 2013-2014 the cases identified increased dramatically,suggesting a high level of under-reporting.Similarly,the proportion of females increased substantially,indicating that passive surveillance may be especially failing this group.An average of 4.9 months of productive time was lost per patient as a consequence of infection.The health consequences included pain,amnesia and physical disability.The social consequences included stigma,dropping out of education,loss of friends and self-esteem.Results obtained from focus group discussions revealed misconceptions among community members which could be attributed to lack of knowledge about rHAT.Conclusions:The social and economic impact of rHAT on rural households and communities is substantial.Improved surveillance and strengthening of local medical services are needed for early and accurate diagnosis.Disease prevention should be prioritised in communities at risk of rHAT,and interventions put in place to prevent zoonotic disease spill over from domestic animals and wildlife.Supportive measures to mitigate the long-term effects of disability due to rHAT are needed.

Factors associated with mobile phone ownership and potential use for rabies vaccination campaigns in southern Malawi

Background:Rabies is a fatal but preventable viral disease,which causes an estimated 59000 human deaths globally every year.The vast majority of human rabies cases are attributable to bites from infected domestic dogs and consequently control of rabies in the dog population through mass vaccination campaigns is considered the most effective method of eliminating the disease.Achieving the WHO target of 70%vaccination coverage has proven challenging in low-resource settings such as Sub Saharan Africa,and lack of public awareness about rabies vaccination campaigns is a major barrier to their success.In this study we surveyed communities in three districts in Southern Malawi to assess the extent of and socio-economic factors associated with mobile phone ownership and explore the attitudes of communities towards the use of short message service(SMS)to inform them of upcoming rabies vaccination clinics.Methods:This study was carried out between 1 October–3 December 2018 during the post-vaccination assessment of the annual dog rabies campaign in Blantyre,Zomba and Chiradzulu districts,Malawi.1882 questionnaires were administered to households in 90 vaccination zones.The surveys gathered data on mobile phone ownership and use,and barriers to mobile phone access.A multivariable regression model was used to understand factors related to mobile phone ownership.Results:Most survey respondents owned or had use of a mobile phone,however there was evidence of an inequality of access,with higher education level,living in Blantyre district and being male positively associated with mobile phone ownership.The principal barrier to mobile phone ownership was the cost of the phone itself.Basic feature phones were most common and few owned smartphones.SMS was commonly used and the main reason for not using SMS was illiteracy.Attitudes to receiving SMS reminders about future rabies vaccination campaigns were positive.Conclusions:The study showed a majority of those surveyed have the use of a mobile phone and most mobile phone owners indicated they would like to receive SMS messages about future rabies vaccination campaigns.This study provides insight into the feasibility of distributing information about rabies vaccination campaigns using mobile phones in Malawi.