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IntroductionMolecular profiling of metastatic breast cancer (MBC) through the widespread use of next-generation sequencing (NGS) has highlighted actionable mutations and driven trials of targeted therapy matched to tumour molecular profiles, with improved outcomes reported using such an approach. Here, we review NGS results and treatment outcomes for a cohort of Asian MBC patients in the phase I unit of a tertiary centre.MethodsPatients with MBC referred to a phase I unit underwent NGS via Ion AmpliSeq Cancer Hotspot v2 (ACH v2, 2014–2017) prior to institutional change to FoundationOne CDx (FM1; 2017–2022). Patients were counselled on findings and enrolled on matched therapeutic trials, where available. Outcomes for all subsequent treatment events were recorded to data cut-off on January 31, 2022.ResultsA total of 215 patients were enrolled with successful NGS in 158 patients. The PI3K/AKT/PTEN pathway was the most altered with one or more of the pathway member genes PIK3/AKT/PTEN affected in 62% (98/158) patients and 43% of tumours harbouring a PIK3CA alteration. Tumour mutational burden (TMB) was reported in 96/109 FM1 sequenced patients, with a mean TMB of 5.04 mt/Mb and 13% (12/96) with TMB ≥ 10 mt/Mb. Treatment outcomes were evaluable in 105/158 patients, with a pooled total of 216 treatment events recorded. Matched treatment was administered in 47/216 (22%) events and associated with prolonged median progression-free survival (PFS) of 21.0 weeks [95% confidence interval (CI) 11.7, 26.0 weeks] versus 12.1 weeks (95% CI 10.0, 15.4 weeks) in unmatched, with hazard ratio (HR) for progression or death of 0.63 (95% CI 0.41, 0.97; p = 0.034). In the subgroup of PIK3/AKT/PTEN-altered MBC, the HR for progression or death was 0.57 (95% CI 0.35, 0.92; p = 0.02), favouring matched treatment. Per-patient overall survival (OS) analysis (n = 105) showed improved survival for patients receiving matched treatment versus unmatched, with median OS (mOS) of 30.1 versus 11.8 months, HR = 0.45 (95% CI 0.24, 0.84; p = 0.013). Objective response rate (ORR) in the overall population was similar in matched and unmatched treatment events (23.7% versus 17.2%, odds ratio of response 1.14 95% CI 0.50, 2.62; p = 0.75).ConclusionsBroad-panel NGS in MBC is feasible, allowing therapeutic matching, which was associated with improvements in PFS and OS.

Integrating imaging sensors and artificial intelligence (AI) have contributed to detecting plant stress symptoms, yet data analysis remains a key challenge. Data challenges include standardized data collection, analysis protocols, selection of imaging sensors and AI algorithms, and finally, data sharing. Here, we present a systematic literature review (SLR) scrutinizing plant imaging and AI for identifying stress responses. We performed a scoping review using specific keywords, namely abiotic and biotic stress, machine learning, plant imaging and deep learning. Next, we used programmable bots to retrieve relevant papers published since 2006. In total, 2,704 papers from 4 databases (Springer, ScienceDirect, PubMed, and Web of Science) were found, accomplished by using a second layer of keywords (e.g., hyperspectral imaging and supervised learning). To bypass the limitations of search engines, we selected OneSearch to unify keywords. We carefully reviewed 262 studies, summarizing key trends in AI algorithms and imaging sensors. We demonstrated that the increased availability of open-source imaging repositories such as PlantVillage or Kaggle has strongly contributed to a widespread shift to deep learning, requiring large datasets to train in stress symptom interpretation. Our review presents current trends in AI-applied algorithms to develop effective methods for plant stress detection using image-based phenotyping. For example, regression algorithms have seen substantial use since 2021. Ultimately, we offer an overview of the course ahead for AI and imaging technologies to predict stress responses. Altogether, this SLR highlights the potential of AI imaging in both biotic and abiotic stress detection to overcome challenges in plant data analysis.

Abstract The subseasonal prediction of polar low (PL) activity is explored using a hybrid statistical‐dynamical approach. A previously developed PL genesis potential index is paired with ECMWF reforecasts and forecasts to predict regional statistics of PL activity across the sub‐Arctic. Regional PL activity is skillfully predicted in all regions at forecast ranges of up to a month. Additionally, the predictability limit of this hybrid framework (estimated using reanalysis data) is found to be highest over the Nordic Seas, Irminger Sea, Labrador Sea, and Bering Sea. We find that climate modes can strongly influence subseasonal prediction skill and are a potential source of predictability. Overall, our results highlight a promising prospect for the subseasonal prediction of PL activity.

Background: Oestrogen receptor positive, human epidermal growth factor receptor-2 (HER2) negative breast cancer (BC) is the most frequently diagnosed BC subtype. Combinations of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) with anti-oestrogen therapy have led to improved survival compared with anti-oestrogen therapy alone for advanced/metastatic BC. The evaluation of CDK4/6i in the real-world facilitates treatment planning, insights into the incidence of drug toxicities, dose modifications including dose delays (DDs) and dose reductions (DRs) and improves prognostic accuracy in subgroups, for example geriatric patients, who are under-represented in clinical trials. Methods: This multi-centre study analysed retrospective and prospective data from 456 patients treated with CDK4/6i between January 2015 and December 2020. We examined patient characteristics, variation in prescribing practices, efficacy and toxicity outcomes. Results: In all, 456 patients were included in this study. The median age was 59 (range: 24–92). In total, 85 (19%) were ⩾70 years old. In all, 122 (27%) and 119 (26%) of patients were treated in the first-line and second-line settings, respectively. In total, 25 (5%), 31 (7%) and 145 (32%) of patients had brain, peritoneum and liver metastasis, respectively, at the time of CDK4/6i initiation. On univariate analysis, heavily pre-treated patients and those with distant metastases, involving the liver, brain or peritoneum, had significantly shorter progression-free survival (PFS) and 24-month overall survival (OS). Elderly patients (⩾70) had a shorter PFS; OS results were not mature. Majority of patients ( n = 362, 80%) initiated treatment with the United States FDA-approved starting dose of CDK4/6i. In all, 330 (72%) had at least one DD and 217 (48%) patients required at least one DR, but these dose modifications were not associated with poorer survival outcomes. Patients age ⩾70 were more likely to require dose modifications leading to a lower treatment dose. The most common reason for DD/DR was neutropenia (60%) and the incidence of febrile neutropenia was only 2%. Conclusions: Our study indicates CDK4/6i is effective and safe. Age ⩾ 70, distant metastases to liver, peritoneal or brain were negative prognostic factors. Age ⩾ 70 was associated with significantly increased requirement for dose modification; however, this did not impact survival outcomes. These findings provide reassurance that survival outcomes are not adversely affected in elderly patients when DD/DR is indicated.

Volume reflection hologram-based sensors are designed to visibly change colour in response to a target stressor or analyte. However, reflection holograms fabricated in thick photopolymer films are highly angularly selective, making these sensors challenging to view and interpret by non-experts. Here, the use of speckle holography to improve the visibility of reflection holograms is presented. A novel recording approach combining speckle recording techniques with Denisyuk reflection recording geometry is described. The recorded speckle reflection grating operates as a series of multiplexed reflection gratings with a range of spatial frequencies, capable of reflecting light at a wider range of angles. A comparative study of the angular and wavelength selectivity of speckle and standard reflection gratings was conducted. The FWHM of the angular selectivity curves of the speckle reflection gratings is doubled (4°) in comparison to standard 4500 lines/mm reflection gratings (2°). The wavelength selectivity FWHM is also doubled from 4.2 to 8.6 nm. The comparative ability of the speckle and standard reflection gratings to act as colour-changing compressional pressure sensors in the 0.88–5.31 MPa range is described. Finally, we present a prototype reflection hologram viewer which enables the easy observation of angularly specific reflection holograms by non-experts.

In this contribution, we present an innovative data-driven model to reconstruct a reliable temporal pattern for time-lagged statistical monetary figures. Our research cuts across several domains regarding the production of robust economic inferences and the bridging of top-down aggregated information from central databases with disaggregated information obtained from local sources or national statistical offices. Our test bed case study is the European Regional Development Fund (ERDF). The application we discuss deals with the reported time lag between the local expenditures of ERDF by beneficiaries in Italian regions and the corresponding payments reported in the European Commission database. Our model reconstructs the timing of these local expenditures by back-dating the observed European Commission reimbursements. The inferred estimates are then validated against the expenditures reported from the Italian National Managing Authorities (NMAs) in terms of cumulative monetary difference. The lower cumulative yearly distance of our modelled expenditures compared to the official European Commission payments confirms the robustness of our model. Using sensitivity analysis, we also analyse the relative importance of the modelling parameters on the cumulative distance between the modelled and reported expenditures. The parameters with the greatest influence on the uncertainty of this distance are the following: first, how the non-clearly regionalised expenditures are attributed to individual regions; and second, the number of backward years that the residuals of the yearly payments are spread onto. In general, the distance between the modelled and reported expenditures can be further reduced by fixing these parameters. However, the gain is only marginal for some regions. The present study paves the way for modelling exercises that are aimed at more reliable estimates of the expenditures on the ground by the ultimate beneficiaries of European funds. Additionally, the output databases can contribute to enhancing the reliability of econometric studies on the effectiveness of European Union (EU) funds.

The lack of large-scale open-source expert-labelled seismic datasets is one of the barriers to applying today’s AI techniques to automatic fault recognition tasks. The dataset present in this article consists of a large number of processed seismic images and their corresponding fault annotations. The processed seismic images, which are originally from a seismic survey called Thebe Gas Field in the Exmouth Plateau of the Carnarvan Basin on the NW shelf of Australia, are represented in Python Numpy format, which can be easily adopted by various AI models and will facilitate cooperation with researchers in the field of computer science. The corresponding fault annotations were firstly manually labelled by expert interpreters of faults from seismic data in order to investigate the structural style and associated evolution of the basin. Then the fault interpretation and seismic survey are processed and collected using Petrel software and Python programs separately. This dataset can help to train, validate, and evaluate the performance of different automatic fault recognition workflow.

Objectives: The aim of this study was to investigate associations between baseline characteristics and CD4 cell count response on first-line antiretroviral therapy and risk of virological failure (VF) with or without drug resistance. Methods: We conducted an analysis of UK Collaborative HIV Cohort data linked to the UK HIV Drug Resistance Database. Inclusion criteria were viral sequence showing no resistance prior to initiation of first-line efavirenz + tenofovir disoproxil fumarate + emtricitabine and virological suppression within 6 months. Outcomes of VF (≥200 copies/mL) with or without drug resistance were assessed using a competing risks approach fitted jointly with a model for CD4 cell count recovery. Hazard ratios for each VF outcome were estimated for baseline CD4 cell count and viral load and characteristics of CD4 cell count response using latent variables on a standard normal scale. Results: A total of 3640 people were included with 338 VF events; corresponding viral sequences were available in 134 with ≥1 resistance mutation in 36. VF with resistance was associated with lower baseline CD4 (0.30, 0.09–0.62), lower CD4 recovery (0.04, 0.00–0.17) and higher CD4 variability (4.40, 1.22–12.68). A different pattern of associations was observed for VF without resistance, but the strength of these results was less consistent across sensitivity analyses. Cumulative incidence of VF with resistance was estimated to be >2% at 3 years for baseline CD4 ≥350 cells/μL. Conclusion: Lower baseline CD4 cell count and suboptimal CD4 recovery are associated with VF with drug resistance. People with low CD4 cell count before ART or with suboptimal CD4 recovery on treatment should be a priority for regimens with high genetic barrier to resistance.

This paper examines governance practices and their impact on the performance of selected Nepalese cooperatives. In order to address the objectives of the study, 400 sample members from eighteen primary cooperatives in provinces 3 and 6 of Nepal have been identified by stratified random sampling technique to collect primary data with a semi-structured questionnaire. The collected data have been analyzed using SPSS (version 23). Statistical tools like regression, correlation and chi-square tests were applied. The findings revealed that there is significant and positive relationship between professionalization; accountability and performance of cooperatives. Similarly, there are insignificant but positive relationships between participation; transparency and performance of cooperatives. However, there is an insignificant and negative relationship between legitimacy and performance of cooperatives. In conclusion, the performance of cooperatives depends on existence of factors of good governance such as legitimacy, participation, professionalization, accountability and transparency with honesty. On the basis of the study, it is concluded that good governance in cooperatives is the single most important panacea to uplift quality of life of members through economic, social, cultural and technological change in their practical lives. The paper contributes to the literature by identifying factors of good governance for performance of cooperatives from a developing country perspective.

Orientation: Management studies too often concentrate on supposedly normal market conditions in stable, developed countries. In reality, most forms of management are conducted in more trying circumstances, and this article seeks to expand knowledge of how it takes place under difficult conditions. Research purpose: This study explored management techniques under wartime conditions exhibited by managers in the banking and mobile telecommunications sectors in Mogadishu, the capital of Somalia. Motivation for the study: Somalia is a fragile state that risks failing its people in many ways, including security, food security and basic public services. One means of compensating for these failures is the private sector’s ability to organise not just business but essential public services when the government is unable to do so. This article studied whether that was taking place. Research approach/design and method: The research was qualitative in nature and featured in-depth, personal interviews with managers and executives in the identified sectors of interest. Respondents were identified through convenience and then purposive snowball sampling techniques. Main findings: It was found that adaptations to managing in wartime could be divided into three main themes: practical aspects of managing in adversity, coping mechanisms and the ethical issues involved in managing without a government. In general, in the absence of a legitimate ruling power or a form of market regulation, managers reverted to the pre-existing tribal system as a means not just of managing transactions but also to instil trust in those transactions. Practical/managerial implications: A model is provided for managing under wartime or similarly difficult situations, which might be adapted to other contexts. Contribution/value-add: This article extends knowledge of how management is conducted in wartime and how managers adapt to adverse conditions.

This paper derives from various pieces of research, quantitative and qualitative, among artisanal food producers in the Perth area of Western Australia. The research had a focus on the marketing aims of artisanal food producers associated with attendance at Victoria Park Farmers’ Market. It was started so as to locate the motivations of these small-scale producers to be involved in food production at all. Major motivational themes quickly emerged. The first was freedom and the second was self-expression, while community feeling was also important as an other-orientated approach, which was slightly contradictory. Sub-themes also emerged, for instance the desire to promote community health. What was not relevant was the drive towards maximising income, creating substantial income, which is from the perspective of entrepreneurship or economic rationality. That rationality derives, of course, from the propositions of classical economics, which has been looking threadbare for some time. Ally the findings here with those from others from research work on consumers at Perth farmers’ markets and consumers of the artisanal producers’ products and this sense of irrationality was further confirmed. Purchasers were little concerned about prices. Ultimately, though, farmers’ markets are characterized by high prices and irrationality in terms of classic supply chain theory, whereby the more that intermediaries are removed, the lower the price should be for the purchaser. That simply does not happen since there is a social element, even a relationship element, that is now being factored into price determination as consumers and farmers come face-to-face.