bluuebunny/crossref_metadata_2025_split huggingface dataset:
2 Learning from a new model of end of life care for older people with frailty/multi-morbidities – the challenges and opportunities for specialist palliative care services
Authors: Noble Jan , Nicholson Caroline , Harris Laura , Richardson Heather 
Published: August 2018

IntroductionBromley Care Coordination (BCC) at St Christopher’s Hospice is an innovative nurse-led community based service to enable patients with advanced illness or frailty thought to be in the last year of life to receive timely and well- coordinated care at home. Commissioned in 2014 by Bromley CCG reaches people who would not traditionally be seen by hospice community care teams.The Bromley Care Coordination Centre offers 24/7 telephone support and home visits to patients providing symptom control pain control and psychological support.AimTo understand patient characteristics end of life needs and BCC service response in order to refine service delivery.MethodsService evaluation using routine collected service data notes and case reviews.ResultsResults since Jan 2014:2200 people have been referred (55% from GP 26% from Hospital 19% other)Of those who have died 70% have died in their own home/care homeAverage age of patients referred 86The ratio of non-cancer to cancer diagnoses is 85%: 15%86% of patients have no other current health care intervention apart from the GP and occasionally a social care agency/provider (16/17 data)39% of patients live alone many more patients live with a spouse who is also frail and elderly.ConclusionsLearning has led to working with a different skill mix developing a ‘stratification’ tool introducing the role of care navigators and volunteers.BCC has extended the hospice’s reach by 50% in one CCG. The next stages are embedding sustainability and implementation in other areas.
25 Evidence based training for hostel staff around supporting homeless people with deteriorating health
Authors: Hudson Briony F , Shulman Caroline , Kennedy Peter , Brophy Niamh , Stone Patrick 
Published: August 2018

IntroductionMany people experiencing homelessness remain in homeless hostels as their health deteriorates due to lack of alternative places of care (Shulmanet al.2017). Palliative care services are rarely involved and hostel staff face significant emotional and practical difficulties (Hudsonet al.2017). We developed evidence-based training for hostel staff around supporting residents with deteriorating health.AimsTo pilot and evaluate the impact of training.MethodsMixed methods pre-and-post training evaluation. Knowledge of palliative care confidence in and openness to supporting residents with deteriorating health and work-related stress were assessed at baseline and immediately post-training using a novel questionnaire. Following training group discussions were facilitated and participants identified team goals for implementation. Additional focus groups were held after three months.ResultsAll staff from two hostels attended 87% completed the course (n=21). Modest improvements in knowledge confidence openness and work-related stress were observed. Participants particularly valued the inclusion of strategies for identifying and addressing their emotional needs. At three months team goals were partially met. Identification and recognition of palliative care needs had improved. However the recovery focused ethos of hostels and significant staff turnover limited change. Systems designed to monitor ‘recovery’ did not accommodate or encourage a person-centred approach for people with deteriorating health.ConclusionsTraining in isolation is not enough for system change. Recommendations include embedding ongoing training into routine practice identifying champions to promote multidisciplinary working and incorporating flexibility in outcome measures to reflect complexity in person-centred care including where recovery may not be realistic.References. Hudson BF, Shulman C, Low J, Hewett N, Daley J, Davis S, Brophy N, Howard D, Vivat B, Kennedy P, Stone P. Challenges to discussing palliative care with people who are homeless: A qualitative study. BMJ Open2017;7:e017502. doi:10.1136/bmjopen-2017-017502. Shulman C, Hudson BF, Low J, Hewett N, Daley J, Kennedy P, et al. Homelessness at the end of life: A qualitative analysis of the barriers in providing palliative care for people who are homeless. Palliative Medicine2017. https://doi.org/10.1177/0269216317717101
39 Improving coordination of care – marie curie nursing service london and cmc
Authors: Ripley Debbie 
Published: August 2018

BackgroundMarie Curie community nurses and health care assistants provide care to terminally ill patients and their families in people’s homes. Due to different computer systems used by NHS trusts it is a challenge to access up to date patient information.In 2016 Marie Curie as a national provider of end of life care applied for a grant and was awarded £1 million from NHS digital to improve nursing care and productivity within the community. This money was used to purchase a tablet for all community staff.Coordinate My Care (CMC) is an NHS database set up in 2012 for urgent care plans to be created for patients to record and share wishes that healthcare professionals can share and access 24/7. CMC is the only London wide data base London Ambulance Service use.Of the 19 000 care plans created to date in London 75% of people have died where they wanted to.Marie Curie Nursing Service provides care across all 32 London Boroughs.Care is currently commissioned 1:1 in patient’s homes 10 pm–7 am.Marie Curie also has two x overnight rapid response services based at Greenwich Hospice and Meadow House Hospice in Ealing. Rapid response provides multiple visits overnight to patients and their families who need symptom control and support.All Marie Curie nurses are being trained to have access to CMC via their Marie Curie tablets.A pilot in nursing homes in South London is being discussed where Marie Curie nurses will be helping staff and patients write their own high-quality care plans.Reference. http://endoflifecareambitions.org.uk/wp-content/uploads/2015/09/Ambitions-for-Palliative-and-End-of-Life-Care.pdf
Primary school achievement and socioeconomic attainment in individuals affected by parental cancer in childhood or adolescence: a Danish nationwide register-based study
Authors: Joergensen Anne Cathrine , Kjaer Urhoj Stine , Nybo Andersen Anne-Marie 
Published: August 2018

BackgroundChildren who experience parental cancer are at increased risk of developing emotional, social, cognitive and behavioural problems. Our aim was to investigate how experience of parental cancer in childhood or adolescence is associated with primary school achievement, educational attainment and income in early adult life.MethodsThis is a register-linkage, prospective study of children born in Denmark from 1978 through 1999 and their parents. Parental cancer experience before the ages of 15 and 18 was identified in the Danish National Patient Registry. Final grade point average (GPA) in ninth grade, educational attainment and disposable personal income at the age of 30 were identified in Statistics Denmark registers. General linear models and multinomial logistic regression were used to estimate beta estimates of GPA, and relative risk ratios (RRR) for lower educational and income levels compared with children without parental cancer, taking parental educational status into account.ResultsChildren who had experienced parental cancer achieved a slightly lower final GPA in ninth grade and had a higher risk of low educational attainment (RRR: 1.20; 95% CI 1.14 to 1.25) and attenuated income at the age of 30 (RRR: 1.11; 95% CI 1.06 to 1.16). For all outcomes, analyses suggested substantial deterioration in achievements in subgroups of children whose parent had a severe cancer type (RRRLow education: 1.52; 95% CI 1.39 to 1.66) or if the parent died of cancer (RRRLow education: 1.61; 95% CI 1.49 to 1.75).ConclusionEducational and socioeconomic attainments in early adulthood were affected negatively in individuals who had experienced parental cancer as children or adolescents. The associations appeared stronger the more severe the cancer was.
Field evaluation of a smartphone-based electronic reader of rapid dual HIV and syphilis point-of-care immunoassays
Authors: Allan-Blitz Lao-Tzu , Vargas Silver K , Konda Kelika A , Herbst de Cortina Sasha , Cáceres Carlos F , Klausner Jeffrey D 
Published: August 2018

ObjectiveElectronic (E) devices read and quantify lateral flow-based rapid tests, providing a novel approach to assay interpretation. We evaluated the performance of one E-reader for two dual HIV and syphilis immunoassays.MethodsWe enrolled men who have sex with men and transgender women >18 years of age seeking medical services at an STD clinic in Lima, Peru, between October 2016 and April 2017. Venous blood was tested using two dual HIV and syphilis antibody immunoassays (SD BIOLINE HIV/Syphilis Duo, Republic of Korea, and First Response HIV 1+2/Syphilis Combo, India). Reference testing included a fourth-generation ELISA for HIV antibodies and use of the Treponema pallidum particle agglutination assay for syphilis antibodies. Trained clinic staff visually inspected the immunoassay results, after which the immunoassays were read by the HRDR-200 E-reader (Cellmic, USA), an optomechanical smartphone attachment. We calculated the concordance of the E-reader with visual inspection, as well as the sensitivity of both rapid immunoassays, in detecting HIV and T. pallidum antibodies.ResultsOn reference testing of 283 participant specimens, 34% had HIV antibodies and 46% had T. pallidum antibodies. Using First Response, the concordance of the E-reader with visual inspection was 97% (95% CI 94% to 99%) for T. pallidum and 97% (95% CI 95% to 99%) for HIV antibodies. Using SD BIOLINE, the concordance of the E-reader with visual inspection was 97% (95% CI 94% to 99%) for T. pallidum and 99% (95% CI 98% to 99%) for HIV antibodies. For both immunoassays, the sensitivity for HIV antibodies was 98% (95% CI 93% to 100%) and the sensitivity for T. pallidum antibodies was 81% (95% CI 73% to 87%).ConclusionsE-reader results correlated well with visual inspection. The sensitivities of both rapid assays were comparable with past reports. Further evaluation of the E-reader is warranted to investigate its utility in data collection, monitoring and documentation of immunoassay results.
Multi-modal Analgesic Strategies for Trauma (MAST): protocol for a pragmatic randomized trial
Authors: Harvin John A , Green Charles E , Vincent Laura E , Motley Kandice L , Podbielski Jeanette , Miller Charles C , Tyson Jon E , Holcomb John B , Wade Charles E , Kao Lillian S 
Published: August 2018

BackgroundPain management after injury is critically important for functional recovery. Although opioids have been a mainstay for treatment of pain, they are associated with adverse events and may contribute to long-term use or abuse. Opioid-minimizing multimodal pain regimens have the potential to reduce exposure to opioids without compromising pain control. This article details an ongoing clinical trial comparing two pill-based, opioid-minimizing, multimodal pain strategies.MethodsThis is a single-center, parallel-group, randomized, controlled comparative effectiveness trial comparing two multimodal pain regimens in adult trauma patients. All patients 16 years and older admitted to the Red Duke Trauma Institute are eligible unless they are pregnant, a prisoner, under observation status, or a non-acute trauma patient. At admission to the trauma service, patients are enrolled and randomized to one of two multimodal pain regimens. The primary outcome is opioid use, measured by morphine milligram equivalents per patient per day. The secondary outcomes include pain scores, ventilator days, hospital and intensive care unit lengths of stay, occurrence of opioid-related complications, hospital and pharmacy costs, and incidence of hospital discharge with opioid prescription. Outcomes will be compared using Bayesian methods.DiscussionThis trial will determine the effectiveness of two multimodal pain treatment strategies on reducing in-hospital opioid exposure in adult trauma patients. Furthermore, it will compare the two strategies on pain control and patient safety. Knowledge gained in this study can improve quality of care at this hospital and other trauma centers regardless of which medication regimen proves superior.
Measurement of nitrate and nitrite in biopsy-sized muscle samples using HPLC
Authors: Troutman Ashley D. , Gallardo Edgar J. , Brown Mary Beth , Coggan Andrew R. 
Published: August 2018

Studies of rats have indicated that skeletal muscle plays a central role in whole-body nitrate ([Formula: see text])/nitrite ([Formula: see text])/nitric oxide (NO) metabolism. Extending these results to humans, however, is challenging due to the small size of needle biopsy samples. We therefore developed a method to precisely and accurately quantify [Formula: see text] and [Formula: see text] in biopsy-sized muscle samples. [Formula: see text] and [Formula: see text] were extracted from rat soleus samples using methanol combined with mechanical homogenization + ultrasound, bead beating, pulverization at liquid N2temperature or pulverization + 0.5% Triton X-100. After centrifugation to remove proteins, [Formula: see text] and [Formula: see text] were measured using HPLC. Mechanical homogenization + ultrasound resulted in the lowest [Formula: see text] content (62 ± 20 pmol/mg), with high variability [coefficient of variation (CV) >50%] across samples from the same muscle. The [Formula: see text]/[Formula: see text] ratio (0.019 ± 0.006) was also elevated, suggestive of [Formula: see text] reduction during tissue processing. Bead beating or pulverization yielded lower [Formula: see text] and slightly higher [Formula: see text] levels, but reproducibility was still poor. Pulverization + 0.5% Triton X-100 provided the highest [Formula: see text] content (124 ± 12 pmol/mg) and lowest [Formula: see text]/[Formula: see text] ratio (0.008 ± 0.001), with the least variability between duplicate samples (CV ~15%). These values are consistent with literature data from larger rat muscle samples analyzed using chemiluminescence. Samples were stable for at least 5 wk at −80°C, provided residual xanthine oxidoreductase activity was blocked using 0.1 mmol/l oxypurinol. We have developed a method capable of measuring [Formula: see text] and [Formula: see text] in <1 mg of muscle. This method should prove highly useful in investigating the role of skeletal muscle in [Formula: see text]/[Formula: see text]/NO metabolism in human health and disease.NEW & NOTEWORTHY Measurement of nitrate and especially nitrite in small, i.e., biopsy-sized, muscle samples is analytically challenging. We have developed a precise, accurate, and convenient method for doing so using an affordable commercial HPLC system.
RAS–MAPK Pathway-Driven Tumor Progression Is Associated with Loss of CIC and Other Genomic Aberrations in Neuroblastoma
Authors: Eleveld Thomas F. , Schild Linda , Koster Jan , Zwijnenburg Danny A. , Alles Lindy K. , Ebus Marli E. , Volckmann Richard , Tijtgat Godelieve A. , van Sluis Peter , Versteeg Rogier , Molenaar Jan J. 
Published: August 2018

Abstract
Mutations affecting the RAS–MAPK pathway frequently occur in relapsed neuroblastoma tumors, which suggests that activation of this pathway is associated with a more aggressive phenotype. To explore this hypothesis, we generated several model systems to define a neuroblastoma RAS–MAPK pathway signature. Activation of this pathway in primary tumors indeed correlated with poor survival and was associated with known activating mutations in ALK and other RAS–MAPK pathway genes. Integrative analysis showed that mutations in PHOX2B, CIC, and DMD were also associated with an activated RAS–MAPK pathway. Mutation of PHOX2B and deletion of CIC in neuroblastoma cell lines induced activation of the RAS–MAPK pathway. This activation was independent of phosphorylated ERK in CIC knockout systems. Furthermore, deletion of CIC caused a significant increase in tumor growth in vivo. These results show that the RAS–MAPK pathway is involved in tumor progression and establish CIC as a powerful tumor suppressor that functions downstream of this pathway in neuroblastoma.
Significance: This work identifies CIC as a powerful tumor suppressor affecting the RAS-MAPK pathway in neuroblastoma and reinforces the importance of mutation-driven activation of this pathway in cancer. Cancer Res; 78(21); 6297–307. ©2018 AACR.
Tailoring Chemotherapy for the African-Centric S47 Variant of TP53
Authors: Barnoud Thibaut , Budina-Kolomets Anna , Basu Subhasree , Leu Julia I.-Ju , Good Madeline , Kung Che-Pei , Liu Jingjing , Liu Qin , Villanueva Jessie , Zhang Rugang , George Donna L. , Murphy Maureen E. 
Published: August 2018

Abstract
The tumor suppressor TP53 is the most frequently mutated gene in human cancer and serves to restrict tumor initiation and progression. Single-nucleotide polymorphisms (SNP) in TP53 and p53 pathway genes can have a marked impact on p53 tumor suppressor function, and some have been associated with increased cancer risk and impaired response to therapy. Approximately 6% of Africans and 1% of African Americans express a p53 allele with a serine instead of proline at position 47 (Pro47Ser). This SNP impairs p53-mediated apoptosis in response to radiation and genotoxic agents and is associated with increased cancer risk in humans and in a mouse model. In this study, we compared the ability of wild-type (WT) and S47 p53 to suppress tumor development and respond to therapy. Our goal was to find therapeutic compounds that are more, not less, efficacious in S47 tumors. We identified the superior efficacy of two agents, cisplatin and BET inhibitors, on S47 tumors compared with WT. Cisplatin caused dramatic decreases in the progression of S47 tumors by activating the p53/PIN1 axis to drive the mitochondrial cell death program. These findings serve as important proof of principle that chemotherapy can be tailored to p53 genotype.
Significance: A rare African-derived radioresistant p53 SNP provides proof of principle that chemotherapy can be tailored to TP53 genotype. Cancer Res; 78(19); 5694–705. ©2018 AACR.
Targeting Myddosome Signaling in Waldenström's Macroglobulinemia with the Interleukin-1 Receptor-Associated Kinase 1/4 Inhibitor R191
Authors: Ni Haiwen , Shirazi Fazal , Baladandayuthapani Veerabhadran , Lin Heather , Kuiatse Isere , Wang Hua , Jones Richard J. , Berkova Zuzana , Hitoshi Yasumichi , Ansell Stephen M. , Treon Steven P. , Thomas Sheeba K. , Lee Hans C. , Wang Zhiqiang , Davis R. Eric , Orlowski Robert Z. 
Published: August 2018

Abstract

Purpose:
Waldenström's macroglobulinemia is an incurable lymphoproliferative disorder driven by an L265P mutation in the myeloid differentiation primary response gene 88 (MYD88), which activates downstream NF-κB signaling through the Myddosome. As this pathway depends in part on activity of interleukin-1 receptor-associated kinases (IRAKs)-1 and -4, we sought to evaluate the potential of the IRAK1/4 inhibitor R191 in preclinical models.

Experimental Design:
Patient-derived cell lines and primary samples were used in both in vitro and in vivo experiments to model Waldenström's macroglobulinemia and its response to IRAK1/4 inhibitors.

Results:
R191 induced a dose- and time-dependent reduction in viability of BCWM.1 and MWCL-1 Waldenström's cell lines, and suppressed activation of IRAK1/4. This was associated with cell-cycle arrest at G0–G1, reduced levels of cyclin-dependent kinases 4 and 6, and induction of apoptosis in cell lines and primary patient samples. Further downstream, R191 exposure led to reduced activation of NF-κB, and of protein kinase B/Akt/mammalian target of rapamycin signaling, whereas expression of a constitutively active Akt mutant induced R191 resistance. Gene expression profiling and gene set enrichment analysis revealed a signature consistent with inhibition of c-Myc and activation of the endoplasmic reticulum stress response. In both subcutaneous and systemic murine models of Waldenström's, R191 showed antitumor activity. Finally, the activity of R191 was enhanced when it was combined with novel chemotherapeutics such as bortezomib, afuresertib, and ibrutinib.

Conclusions:
Taken together, these data support the translation of R191 as an approach to target IRAK1/4 to the clinic for patients with Waldenström's macroglobulinemia.
Novel lncRNA LINC00844 Regulates Prostate Cancer Cell Migration and Invasion through AR Signaling
Authors: Lingadahalli Shreyas , Jadhao Sudhir , Sung Ying Ying , Chen Mi , Hu Lingling , Chen Xin , Cheung Edwin 
Published: August 2018

Abstract

The human genome is mostly transcribed, yielding a rich repository of noncoding transcripts that are involved in a myriad of biological processes including cancer. However, how many noncoding transcripts such as long noncoding RNAs (lncRNA) function in cancer is still unclear. This study identified a novel set of clinically relevant androgen-regulated lncRNAs in prostate cancer. Among this group, LINC00844 was demonstrated to be a direct androgen-regulated target that is actively transcribed in androgen receptor (AR)–dependent prostate cancer cells. The expression of LINC00844 is higher in normal prostate compared with malignant and metastatic prostate cancer clinical specimens, and patients with low expression had a poor prognosis and significantly increased biochemical recurrence, suggesting LINC00844 functions in suppressing tumor progression and metastasis. Indeed, in vitro loss-of-function studies revealed that LINC00844 prevents prostate cancer cell migration and invasion. Moreover, findings from gene expression profiling analysis indicated that LINC00844 functions in trans, affecting global androgen-regulated gene transcription. Mechanistic evidence reveals that LINC00844 is important in facilitating AR binding to the chromatin. Finally, LINC00844 mediates its phenotypic effects in part by activating the expression of NDRG1, a crucial cancer metastasis suppressor. Collectively, LINC00844 is a novel coregulator of AR that plays a central role in the androgen transcriptional network and the development and progression of prostate cancer.

Implications:
This study highlights the function of the lncRNA, LINC00844, in regulating global AR-regulated genes in prostate cancer by modulating AR binding to chromatin.
Augustus’ “New” Festival: The Centrality of Married Women’s Rituals at the Ludi Saeculares of 17 BCE
Authors: Darja Šterbenc Erker 
Published: August 2018

AbstractThe article explores how Augustus and the priesthood of theXVviri sacris faciundisorganized and performed the rituals for celebrating a new era (ludi saeculares) under the rule of the gods Apollo and Diana. In the Republic, it had been a woman’s personal decision whether or not to take part in women’s festivals. However, theXVviricommanded that 110 married women (matronae) perform rituals (supplications and sacrifices) on the Capitoline. This article argues for the novelty of such a custom, in that it was a new form of top-down appeal tomatronaeto honor the gods in public festivals. The article also argues for the centrality of rituals of thematronaein the festival. At theludi saeculares, the cooperation between men (theXVviri) andmatronaewas ritually staged and seen as indispensable for ensuring the continuity of Rome.