The Second International Nurse Rostering Competition

This paper reports on the Second International Nurse Rostering Competition (INRC-II). Its contributions are (1) a new problem formulation which, differently from INRC-I, is a multi-stage procedure, (2) a competition environment that, as in INRC-I, will continue to serve as a growing testbed for search approaches to the INRC-II problem, and (3) final results of the competition. We discuss also the competition environment, which is an infrastructure including problem and instance definitions, testbeds, validation/simulation tools and rules. The hardness of the competition instances has been evaluated through the behaviour of our own solvers, and confirmed by the solvers of the participants. Finally, we discuss general issues about both nurse rostering problems and optimisation competitions in general.PostprintPeer reviewe

Event-Free Survival in Patients with Early HER2-Positive Breast Cancer with a Pathological Complete Response after HER2-Targeted Therapy: A Pooled Analysis

Early breast cancer; Event-free survival; Pathologic complete responseCáncer de mama temprano; Supervivencia libre de eventos; Respuesta patológica completaCàncer de mama precoç; Supervivència lliure d'esdeveniments; Resposta patològica completaThe standard-of-care for patients with pathological complete response (pCR) after neoadjuvant human epidermal growth factor receptor 2 (HER2)-targeted therapy plus chemotherapy is continuation of HER2-targeted therapy in the adjuvant setting. Our objective was to evaluate risk of recurrence or death in these patients and determine if outcomes differed by the HER2-targeted regimen received in each setting. We analyzed patient-level data from five randomized trials evaluating trastuzumab, pertuzumab, or both as part of systemic neoadjuvant and adjuvant therapy for HER2-positive early breast cancer, and assessed event-free survival (EFS) in 1763 patients. Patients with pCR had decreased risk of an EFS event versus those with residual disease (unadjusted hazard ratio [HR] = 0.35; 95% confidence interval [CI]: 0.27–0.46). Regardless of pCR status, after adjusting for baseline factors, reduction in EFS event risk was greater in patients administered pertuzumab/trastuzumab in both settings versus those administered only trastuzumab in both settings (HR = 0.36; 95% CI: 0.26–0.49), or pertuzumab/trastuzumab in the neoadjuvant setting and only trastuzumab in the adjuvant setting (HR = 0.67; 95% CI: 0.47–0.96). Patients with pCR had longer EFS than those with residual disease. Patients treated with pertuzumab/trastuzumab in both the neoadjuvant and adjuvant settings had the lowest risk of breast cancer recurrence.The analysis was funded by F. Hoffmann-La Roche, Ltd

Apoptosis and antigen receptor function in T and B cells following exposure to herpes simplex virus

AbstractT cells are an essential component of the immune response against herpes simplex virus (HSV) infection. We previously reported that incubation of T cells with HSV-infected fibroblasts inhibits subsequent T cell antigen receptor signal transduction. In the current study, we found that incubation of T cells with HSV-infected fibroblasts also leads to apoptosis in exposed T cells. Apoptosis was observed in Jurkat cells, a T cell leukemia line, and also in CD4+ cells isolated from human peripheral blood mononuclear cells. Direct infection of these cells with HSV also resulted in apoptosis. Clinical isolates of both HSV type 1 and 2 induced apoptosis in infected T cells at comparable levels to cells infected with laboratory strains of HSV, suggesting an immune evasion mechanism that may be clinically relevant. Further understanding of these viral immune evasion mechanisms could be exploited for better management of HSV infection

Straightforward synthesis of 1-alkyl-2-(trifluoromethyl)aziridines starting from 1,1,1-trifluoroacetone

An efficient and straightforward approach towards the synthesis of 1-alkyl-2-(trifluoromethyl)aziridines starting from 1,1,1-trifluoroacetone via imination, alpha-chlorination, hydride reduction and ring closure was developed. In addition, novel primary beta-iodo amines were obtained by regioselective ring opening of these 2-(trifluoromethyl)aziridines using alkyl iodides, and their synthetic potential was demonstrated by converting them into novel alpha-CF(3)-beta-phenylethylamines upon treatment with lithium diphenylcuprate

Users' perceptions of the contribution of a University green roof to sustainable development

Universities are well placed to adopt and use the UN Sustainable Development Goals (SDGs) on their campuses to educate and showcase how the SDGs can be delivered in the built environment. Green infrastructure, such as green roofs, green walls, or green parks, are highly visual implementations with environmental and social benefits that contribute to several SDGs, such as 3 (good health and wellbeing), 10 (reduced inequalities), 11 (sustainable cities and communities), 13 (climate action) and 15 (life on land). These features may be referenced in sustainability teaching and learning, which may raise and heighten awareness of the social, economic, and environmental benefits of green infrastructure. In this study, we explored users’ perceptions of the extent to which a university campus green roof contributes to the SDGs and whether users focussed more on its social or environmental benefits. Statistical analyses, namely independent samples t-tests and analysis of variance, were conducted to determine what influenced users’ perceptions of the green roof. The analyses revealed that users’ perceptions did not differ largely by sociodemographic characteristics, though students perceived the social benefits as greater than university staff. Those with greater knowledge of green roofs perceived its environmental benefits as greater, but not the social benefits. The findings demonstrate the importance of green infrastructure on university campuses for encouraging engagement with the SDGs, whilst indicating that knowledge of such infrastructure increases appreciation of their environmental credentials

Silicon-based photonic crystals fabricated using proton beam writing combined with electrochemical etching method

A method for fabrication of three-dimensional (3D) silicon nanostructures based on selective formation of porous silicon using ion beam irradiation of bulk p-type silicon followed by electrochemical etching is shown. It opens a route towards the fabrication of two-dimensional (2D) and 3D silicon-based photonic crystals with high flexibility and industrial compatibility. In this work, we present the fabrication of 2D photonic lattice and photonic slab structures and propose a process for the fabrication of 3D woodpile photonic crystals based on this approach. Simulated results of photonic band structures for the fabricated 2D photonic crystals show the presence of TE or TM gap in mid-infrared rang

Comparison of carboplatin versus cisplatin in the treatment of paediatric extracranial malignant germ cell tumours: A report of the Malignant Germ Cell International Consortium.

PURPOSE: To compare the outcomes of paediatric and adolescent extracranial malignant germ cell tumour (GCT) patients treated with either carboplatin or cisplatin on clinical trials conducted by the Children's Oncology Group (COG) and the Children's Cancer and Leukaemia Group (CCLG). METHODS: The Malignant Germ Cell International Consortium (MaGIC) has created a database of the GCT clinical trials conducted since 1983 by COG (United States, Canada and Australia), which used cisplatin-based regimens, and by CCLG (United Kingdom), which used carboplatin-based regimens. Using the parametric cure model, this study compared the overall 4-year event-free survival (EFS), stratified by age, stage, site and the a-priori defined MaGIC 'risk' groups: standard risk ((SR) 1 (EFS >80%; age 80%, age ≥ 11y) and poor risk (PR) (EFS ≤ 70%, age ≥ 11y). RESULTS: Cisplatin-based therapy was used in 620 patients; carboplatin was used in 163 patients. In the overall multivariate cure model, the two regimens did not differ significantly (cisplatin: 4-year EFS 86%; 95% confidence interval (CI) 83-89% versus carboplatin 4-year EFS 86%; 95% CI 79-90%; p = 0.87). No significant differences were noted in stratified analyses by site, stage, age and MaGIC risk groups: SR1 (p = 0.20), SR2 (p = 0.55) or PR (p = 0.72) patients. CONCLUSIONS: In these trials conducted contemporaneously, there is no significant difference in outcome observed overall, or any subset of patients, who were treated with regimens containing cisplatin versus carboplatin These results suggested sufficient equipoise to justify a randomised trial to evaluate the effectiveness of carboplatin versus cisplatin in the treatment of children, adolescents and young adults with standard risk GCT, which is currently underway

Ets homologous factor regulates pathways controlling response to injury in airway epithelial cells

Ets homologous factor (EHF) is an Ets family transcription factor expressed in many epithelial cell types including those lining the respiratory system. Disruption of the airway epithelium is central to many lung diseases, and a network of transcription factors coordinates its normal function. EHF can act as a transcriptional activator or a repressor, though its targets in lung epithelial cells are largely uncharacterized. Chromatin immunoprecipitation followed by deep sequencing (ChIP-seq), showed that the majority of EHF binding sites in lung epithelial cells are intergenic or intronic and coincide with putative enhancers, marked by specific histone modifications. EHF occupies many genomic sites that are close to genes involved in intercellular and cell–matrix adhesion. RNA-seq after EHF depletion or overexpression showed significant alterations in the expression of genes involved in response to wounding. EHF knockdown also targeted genes in pathways of epithelial development and differentiation and locomotory behavior. These changes in gene expression coincided with alterations in cellular phenotype including slowed wound closure and increased transepithelial resistance. Our data suggest that EHF regulates gene pathways critical for epithelial response to injury, including those involved in maintenance of barrier function, inflammation and efficient wound repair

Local-regional recurrence in women with small node-negative, HER2-positive breast cancer: results from a prospective multi-institutional study (the APT trial).

PurposeWomen with HER2-positive breast cancer treated prior to effective anti-HER2 therapy have higher rates of local-regional recurrence (LRR) than those with HER2-negative disease. Effective systemic therapy, however, has been shown to decrease LRR. This study examines LRR in women with HER2-positive breast cancer treated on a single-arm prospective multicenter trial of adjuvant trastuzumab (H) and paclitaxel (T).MethodsPatients with HER2-positive tumors ≤ 3.0 cm with negative axillary nodes or micrometastatic disease were eligible. Systemic therapy included weekly T and H for 12 weeks followed by continuation of H to complete 1 year. Radiation therapy (RT) was required following breast-conserving surgery (BCS), but dose and fields were not specified. Disease-free survival (DFS) and LRR-free survival were calculated using the Kaplan-Meier method.ResultsOf the 410 patients enrolled from September 2007 to September 2010, 406 initiated protocol therapy and formed the basis of this analysis. A total of 272 (67%) had hormone receptor-positive tumors. Of 162 patients undergoing mastectomy, local therapy records were unavailable for two. None of the 160 for whom records were available received RT. Among 244 BCS patients, detailed RT records were available for 217 (89%). With a median follow-up of 6.5 years, 7-year DFS was 93.3% (95% CI 90.4-96.2), and LRR-free survival was 98.6% (95% CI 97.4-99.8).ConclusionLRR in this select group of early-stage patients with HER2-positive disease receiving effective anti-HER2 therapy is extremely low. If confirmed in additional studies, future investigational efforts should focus on de-escalating local therapy