bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of three common nutritional screening tools with the new European Society for Clinical Nutrition and Metabolism (ESPEN) criteria for malnutrition among patients with geriatric gastrointestinal cancer: a prospective study in China
Authors: Ye Xiao-Jun , Ji Yan-Bin , Ma Bing-Wei , Huang Dong-Dong , Chen Wei-Zhe , Pan Zong-You , Shen Xian , Zhuang Cheng-Le , Yu Zhen
Published: April 2018

Objective

The aim of this study was to evaluate and compare three common nutritional screening tools with the new European Society for Clinical Nutrition and Metabolism (ESPEN) diagnostic criteria for malnutrition among elderly patients with gastrointestinal cancer.

Research methodsandprocedures

Nutritional screening tools, including the Nutritional Risk Screening 2002 (NRS 2002), the Malnutrition Universal Screening Tool (MUST) and the Short Form of Mini Nutritional Assessment (MNA-SF), were applied to 255 patients with gastrointestinal cancer. We compared the diagnostic values of these tools for malnutrition, using the new ESPEN diagnostic criteria for malnutrition as the ‘gold standards’.

Results

According to the new ESPEN diagnostic criteria for malnutrition, 20% of the patients were diagnosed as malnourished. With the use of NRS 2002, 52.2% of the patients were found to be at high risk of malnutrition; with the use of MUST, 37.6% of the patients were found to be at moderate/high risk of malnutrition; and according to MNA-SF, 47.8% of the patients were found to be at nutritional risk. MUST was best correlated with the ESPEN diagnostic criteria (К=0.530, p<0.001) compared with NRS 2002 (К=0.312, p<0.001) and MNA-SF (К=0.380, p<0.001). The receiver operating characteristic curve of MUST had the highest area under the curve (AUC) compared with NRS 2002 and MNA-SF.

Conclusions

Among the tools, MUST was found to perform the best in identifyingmalnourished elderly patients with gastrointestinal cancer distinguished by the new ESPEN diagnostic criteria for malnutrition. Nevertheless, further studies are needed to verify our findings.

Trial registration number

ChiCTR-RRC-16009831; Pre-results.
Gender inequalities in the association between area deprivation and perceived social support: a cross-sectional multilevel analysis at the municipality level in Germany
Authors: Mena Emily , Kroll Lars Eric , Maier Werner , Bolte Gabriele
Published: April 2018

Objectives

To investigate the association between area deprivation at municipality level with low perceived social support, independent of individual socioeconomic position and demographic characteristics. To assess whether there are gender inequalities in this association.

Design

Cross-sectional multilevel analysis of survey data.

Setting

Germany.

Participants

3350 men and 3665 women living in 167 municipalities throughout Germany participating in the ‘German Health Interview and Examination Survey for Adults’ (DEGS1 2008–2011) as part of the national health monitoring.

Outcome

Perceived social support as measured by Oslo-3 Social Support Scale.

Results

Prevalence of low perceived social support was 11.4% in men and 11.1% in women. Low social support was associated in men and women with sociodemographic characteristics that indicate more disadvantaged living situations. Taking these individual-level characteristics into account, municipal-level deprivation was independently associated with low perceived social support in men (OR for the most deprived quintile: 1.80 (95% CI 1.14 to 2.84)), but not in women (OR 1.22 (95% CI 0.78 to 1.90)).

Conclusion

The results of our multilevel analysis suggest that there are gender inequalities in the association of municipal-level deprivation with the prevalence of low perceived social support in Germany independent of individual socioeconomic position. Community health interventions aiming at promotion of social support among residents might profit from a further understanding of the observed gender differences.
Effect of maternal age on facility-based delivery: analysis of first-order births in 34 countries of sub-Saharan Africa using demographic and health survey data
Authors: Dunlop Catherine L , Benova Lenka , Campbell Oona
Published: April 2018

Objectives

Increasing access to skilled birth attendance, usually via childbirth in health facilities, is a key intervention to reduce maternal and perinatal mortality and morbidity. Yet, in some countries of sub-Saharan Africa, the uptake is <50%. Age and parity are determinants of facility-based delivery, but are strongly correlated in high fertility settings. This analysis assessed the independent effect of age on facility-based delivery by restricting to first-order births. It was hypothesised that older first-time mothers in this setting might have lower uptake of facility-based deliveries than women in the most common age groups for first birth.

Setting

The most recent Demographic and Health Surveys from 34 sub-Saharan African countries were used to assess women’s delivery locations.

Participants

72 772 women having their first birth in the 5 years preceding the surveys were included in the analysis.

Primary and secondary outcome measures

Proportions and 95% CIs of facility-based deliveries were estimated overall and by country. Multivariable logistic regression was used to calculate the odds of facility-based delivery for different maternal age groups (15–19, 20–24 and ≥25 years) for a pooled sample of all countries.

Results

59.9% of women had a facility-based delivery for their first birth (95% CI 58.6 to 61.2), ranging from 19.4% in Chad to 96.6% in Rwanda. Compared with women aged 15–19 years, the adjusted odds of having a facility-based delivery for those aged 20–24 was 1.4 (95% CI 1.3 to 1.5, p<0.001) and for those aged ≥25, 1.9 (95% CI 1.6 to 2.2, p<0.001).

Conclusions

Older age at first birth was independently associated with significantly higher odds of facility-based delivery. This went against the hypothesis. Further mixed-method research is needed to explore how increased age improves uptake of facility-based delivery. Promoting facility-based delivery, while ensuring quality of care, should be prioritised to improve birth outcomes in sub-Saharan Africa.
Associations between blood cadmium levels and cognitive function in a cross-sectional study of US adults aged 60 years or older
Authors: Li Hongyu , Wang Zhihui , Fu Zhen , Yan Mingming , Wu Nanjin , Wu Hongyan , Yin Ping
Published: April 2018

Objectives

The relationship between cadmium exposure and cognition has been well studied in children. However, the association between environmental cadmium exposure and cognitive function has not been researched extensively in older adults. Our goal was to evaluate the association between cognitive function and blood cadmium levels in US adults aged 60 years or older.

Design

A cross-sectional study.

Setting

The US National Health and Nutrition Examination Survey (NHANES).

Participants

A total of 2068 adults aged 60 years or older who completed four cognitive assessment tests and blood cadmium detection in two waves of NHANES (2011–2014).

Main outcome measures

Cognitive assessment was conducted by household interview or at a Mobile Examination Center (MEC) using the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) Word List Learning Test, the CERAD Word List Recall Test, the Animal Fluency Test and the Digit Symbol Substitution Test (DSST). We created a composite cognitive z-score to represent global cognitive function.

Results

The median blood cadmium concentration in the study participants was 0.35 µg/L, and the IQR was 0.24–0.56 µg/L. In linear regression analyses, adjusting for demographics, behaviour and medical history, blood cadmium as a continuous variable was inversely associated with the composite z-score (μg/L, β=−0.11, 95% CI −0.20 to −0.03). Similarly, there was a significant association between quartiles of blood cadmium and composite z-score, with somewhat lower scores in the upper quartile of exposure (blood cadmium ≥0.63 µg/L) compared with those in the lower quartile of exposure (blood cadmium <0.25 µg/L) (μg/L, β=−0.14, 95% CI −0.25 to –0.03), and there was a trend by quartiles of blood cadmium (P<0.0001).

Conclusions

Our findings suggest that increased blood cadmium is associated with worse cognitive function in adults aged 60 years or older in the USA.
Current practice of usual clinic blood pressure measurement in people with and without diabetes: a survey and prospective ‘mystery shopper’ study in UK primary care
Authors: Stevens Sarah L , McManus Richard J , Stevens Richard John
Published: April 2018

Objectives

Hypertension trials and epidemiological studies use multiple clinic blood pressure (BP) measurements at each visit. Repeat measurement is also recommended in international guidance; however, little is known about how BP is measured routinely. This is important for individual patient management and because routinely recorded readings form part of research databases. We aimed to determine the current practice of BP measurement during routine general practice appointments.

Design

(1) An online cross-sectional survey and (2) a prospective ‘mystery shopper’ study where patients agreed to report how BP was measured during their next appointment.

Setting

Primary care.

Participants

Patient charity/involvement group members completing an online survey between July 2015 and January 2016. 334 participants completed the prospective study (51.5% male, mean age=59.3 years) of which 279 (83.5%) had diabetes.

Primary outcome

Proportion of patients having BP measured according to guidelines.

Results

217 participants with (183) and without diabetes (34) had their BP measured at their last appointment. BP was measured in line with UK guidance in 63.7% and 60.0% of participants with and without diabetes, respectively. Initial pressures were significantly higher in those who had their BP measured more than once compared with only once (p=0.016/0.089 systolic and p<0.001/p=0.022 diastolic, in patients with/without diabetes, respectively).

Conclusions

Current practice of routine BP measurement in UK primary care is often concordant with guidelines for repeat measurement. Further studies are required to confirm findings in broader populations, to confirm when a third repeat reading is obtained routinely and to assess adherence to other aspects of BP measurement guidance.
‘Re-engage’ pilot study protocol: a nurse-led eHealth intervention to re-engage, educate and empower childhood cancer survivors
Authors: Signorelli Christina , Wakefield Claire E , Johnston Karen A , Fardell Joanna E , Brierley Mary-Ellen E , Thornton-Benko Elysia , Foreman Tali , Webber Kate , Wallace W Hamish , Cohn Richard J
Published: April 2018

Introduction

Many childhood cancer survivors are disengaged from cancer-related follow-up care despite being at high risk of treatment-related late effects. Innovative models of long-term follow-up (LTFU) care to manage ongoing treatment-related complications are needed. ‘Re-engage’ is a nurse-led eHealth intervention designed to improve survivors’ health-related self-efficacy, targeted at survivors disengaged from follow-up. Re-engage aims to overcome survivor- and parent-reported barriers to care and ensure survivors receive the care most appropriate to their risk level.

Methods and analysis

This study will recruit 30 Australian childhood cancer survivors who are not receiving any cancer-related care. Participation involves two online/telephone consultations with a survivorship nurse for medical assessment, a case review, risk stratification and creation of a care plan by a multidisciplinary team of specialists. We will assess the feasibility of implementing ‘Re-engage’ and its acceptability to participants and health professionals involved. The primary outcome will be survivors’ health-related self-efficacy, measured at baseline and 1 and 6 months postintervention. Secondary outcomes will include the effect of ‘Re-engage’ on survivors’ health behaviours and beliefs, engagement in healthcare, information needs and emotional well-being. We will also document the cost per patient to deliver ‘Re-engage’. If Re-engage is acceptable, feasible and demonstrates early efficacy, it may have the potential to empower survivors in coordinating their complex care, improving survivors’ long-term engagement and satisfaction with care. Ideally, it will be implemented into clinical practice to recall survivors lost to follow-up and reduce the ongoing burden of treatment for childhood cancer.

Ethics and dissemination

The study protocol has been approved by the South Eastern Sydney Local Health District Human Research Ethics Committee (reference number: 16/366). The results will be disseminated in peer-reviewed journals and at scientific conferences. A lay summary will be published on the Behavioural Sciences Unit website.

Trial registration number

ACTRN12618000194268.
Cardiac rehabilitation and physical activity: systematic review and meta-analysis
Authors: Dibben Grace Olivia , Dalal Hasnain M , Taylor Rod S , Doherty Patrick , Tang Lars Hermann , Hillsdon Melvyn
Published: April 2018

Objective

To undertake a systematic review and meta-analysis to assess the impact of cardiac rehabilitation (CR) on physical activity (PA) levels of patients with heart disease and the methodological quality of these studies.

Methods

Databases (MEDLINE, EMBASE, CENTRAL, CINAHL, PsychINFO and SportDiscus) were searched without language restriction from inception to January 2017 for randomised controlled trials (RCTs) comparing CR to usual care control in adults with heart failure (HF) or coronary heart disease (CHD) and measuring PA subjectively or objectively. The direction of PA difference between CR and control was summarised using vote counting (ie, counting the positive, negative and non-significant results) and meta-analysis.

Results

Forty RCTs, (6480 patients: 5825 CHD, 655 HF) were included with 26% (38/145) PA results showing a statistically significant improvement in PA levels with CR compared with control. This pattern of results appeared consistent regardless of type of CR intervention (comprehensive vs exercise-only) or PA measurement (objective vs subjective). Meta-analysis showed PA increases in the metrics of steps/day (1423, 95% CI 757.07 to 2089.43, p<0.0001) and proportion of patients categorised as physically active (relative risk 1.55, 95% CI 1.19 to 2.02, p=0.001). The included trials were at high risk of bias, and the quality of the PA assessment and reporting was relatively poor.

Conclusion

Overall, there is moderate evidence of an increase in PA with CR participation compared with control. High-quality trials are required, with robust PA measurement and data analysis methods, to assess if CR definitely leads to important improvements in PA.
Exercise testing in patients with asymptomatic moderate or severe aortic stenosis
Authors: Saeed Sahrai , Rajani Ronak , Seifert Reinhard , Parkin Denise , Chambers John Boyd
Published: April 2018

Objective

To assess the safety and tolerability of treadmill exercise testing and the association of revealed symptoms with outcome in apparently asymptomatic patients with moderate to severe aortic stenosis (AS).

Methods

A retrospective cohort study of 316 patients (age 65±12 years, 67% men) with moderate and severe AS who underwent echocardiography and modified Bruce exercise treadmill tests (ETTs) at a specialist valve clinic. The outcome measures were aortic valve replacement (AVR), all-cause mortality or a composite of AVR and all-cause mortality.

Results

At baseline, there were 210 (66%) patients with moderate and 106 (34%) with severe AS. There were 264 (83%) events. 234 (74%) patients reached an indication for AVR, 145 (69%) with moderate and 88 (83%) with severe AS (p<0.05). Of the 30 (9%) deaths recoded during follow-up, 20 (67%) were cardiovascular related. In total, 797 exercise tests (mean 2.5±2.1 per patient) were performed. No serious adverse events were observed. The prevalence of revealed symptoms at baseline ETT was 29% (n=91) and was significantly higher in severe AS compared with moderate AS (38%vs23%, p=0.008). Symptoms were revealed in 18%–59% of patients during serial ETT conducted over a follow-up period of 34.9 (SD 35.1) months. The event-free survival at 24 months with revealed symptoms was 46%±4% and without revealed symptoms was 70%±4%.

Conclusions

ETT in patients with moderate or severe AS is safe and tolerable. Serial exercise testing is useful to reveal symptoms not volunteered on the history and adds incremental prognostic information to baseline testing.
Lessons identified from the 2017 Manchester and London terrorism incidents. Part 1: introduction and the prehospital phase
Authors: Hunt Paul
Published: April 2018

This is the first article in a three-part series detailing the lessons identified during the NHS England clinical debrief meetings which followed the response to the 2017 Manchester and London terrorist incidents. It covers the prehospital phase including the overall key learning points, timeline information, scene challenges, resource utilisation, triage, distribution and helicopter emergency medical service feedback.
New regular black hole solutions and other electrically charged compact objects with a de Sitter core and a matter layer
Authors: Masa Angel D. D. , de Oliveira Enesson S. , Zanchin Vilson T.
Published: April 2018

The main objective of this work is the construction of regular black hole solutions in the context of the Einstein–Maxwell theory. The strategy is to match an interior regular solution to an exterior electrovacuum solution. With this purpose, we first write explicitly the Einstein field equations for the interior regular region. We take an electrically charged nonisotropic fluid, which presents spherical symmetry and a de Sitter type equation of state, where the radial pressure [Formula: see text] is equal to the negative of energy density [Formula: see text], [Formula: see text]. Then, two solutions for the Einstein equations are built, a regular interior solution for the region with matter satisfying a de Sitter equation of state, and an external solution for the region outside the matter, that corresponds to the Reissner–Nordström metric. To complete the solution we apply the Darmois–Israel junction conditions with a timelike thin shell at the matching surface. It is assumed that the matching surface is composed by a thin shell of matter, i.e. a surface layer in the form of a perfect fluid obeying a barotropic equation of state, [Formula: see text] and [Formula: see text] being the intrinsic pressure and energy density of the shell, respectively, and [Formula: see text] a constant parameter. We show that there are electrically charged regular black hole solutions and other compact objects for specific choices of [Formula: see text] and of the other parameters of the model. Some properties the objects are investigated.
The Interplay of Environmental Assessment Methods; Characterising the Institutional Background in Egypt
Authors: Ismaeel Walaa S. E. , Elsayed Marwa Adel
Published: April 2018

The paper presents an “Analytical Interdisciplinary Methodological Framework” (AIMF) to promote the institutional role of environmental assessment in Egypt. This is based on two main factors; the institutional procedure and application implementation, as well as factors influencing the decision-making process. The study starts with reviewing the levels of environmental assessment; Life Cycle Assessment (LCA), Environmental Impact Assessment (EIA) and Strategic Environmental Assessment (SEA); noting that each level builds from its subsequent level in an attempt to constitute an additive cumulative benefit. This analysis is coupled with structured interviews and designed questionnaires for local planning professionals to investigate the external and internal factors affecting the application of environmental assessment systems in Egypt. This is developed into an interlacing scheme of a sort of continuous process that considers their application status, construction of systems, country laws, and technical aspects. A scoring evaluation matrix has been distributed among the same group of planning professionals to compare the current status and proposed framework of environmental assessment. Eventually, this qualitative investigation provides a novel approach for characterising the institutional background of environmental assessment in Egypt while exploring the interplay and progression between these successive levels of assessment, particularly for low and middle-income countries such as Egypt.
German petroleum geologists and World War II
Authors: Kölbl-Ebert Martina
Published: April 2018

In the 1930s, Alfred Bentz, August Moos and Karl Krejci-Graf were among the most noteworthy petroleum geologists in Germany. Being scientific modernists, they systematized the search for oil, introducing modern exploration methods. All three, at some stage, worked for the German state on providing the petroleum needed by the German military during World War II. The three colleagues seem to have had an amicable relationship. They were, however, very different. Bentz was not a member of the National Socialist party but obviously lent his expertise to the regime; as did Krejci-Graf, who, although also was not a party member, was a member of the SS, whereas Moos, due to his Jewish background, was murdered in January 1945 in the concentration camp of Buchenwald. This paper endeavours to sketch the lives of the three colleagues, highlighting their relationship and the interconnectedness of contemporary moral issues with professional and scientific demands.
Characterizing 3D Floating Gate NAND Flash
Authors: Xiong Qin , Wu Fei , Lu Zhonghai , Zhu Yue , Zhou You , Chu Yibing , Xie Changsheng , Huang Ping
Published: April 2018

As both NAND flash memory manufacturers and users are turning their attentions from planar architecture towards three-dimensional (3D) architecture, it becomes critical and urgent to understand the characteristics of 3D NAND flash memory. These characteristics, especially those different from planar NAND flash, can significantly affect design choices of flash management techniques. In this article, we present a characterization study on the state-of-the-art 3D floating gate (FG) NAND flash memory through comprehensive experiments on an FPGA-based 3D NAND flash evaluation platform. We make distinct observations on its performance and reliability, such as operation latencies and various error patterns, followed by careful analyses from physical and circuit-level perspectives. Although 3D FG NAND flash provides much higher storage densities than planar NAND flash, it faces new performance challenges of garbage collection overhead and program performance variations and more complicated reliability issues due to, e.g., distinct location dependence and value dependence of errors. We also summarize the differences between 3D FG NAND flash and planar NAND flash and discuss implications on the designs of NAND flash management techniques brought by the architecture innovation. We believe that our work will facilitate developing novel 3D FG NAND flash-oriented designs to achieve better performance and reliability.
Path ORAM
Authors: Stefanov Emil , Dijk Marten Van , Shi Elaine , Chan T.-H. Hubert , Fletcher Christopher , Ren Ling , Yu Xiangyao , Devadas Srinivas
Published: April 2018

We present Path ORAM, an extremely simple Oblivious RAM protocol with a small amount of client storage. Partly due to its simplicity, Path ORAM is the most practical ORAM scheme known to date with small client storage. We formally prove that Path ORAM has a
O
(log
N
) bandwidth cost for blocks of size
B
= Ω (log
2
N
) bits. For such block sizes, Path ORAM is asymptotically better than the best-known ORAM schemes with small client storage. Due to its practicality, Path ORAM has been adopted in the design of secure processors since its proposal.
Equivalence of Deterministic Top-Down Tree-to-String Transducers Is Decidable
Authors: Seidl Helmut , Maneth Sebastian , Kemper Gregor
Published: April 2018

We prove that equivalence of deterministic top-down tree-to-string transducers is decidable, thus solving a long-standing open problem in formal language theory. We also present efficient algorithms for subclasses: for linear transducers or total transducers with unary output alphabet (over a given top-down regular domain language), as well as for transducers with the single-use restriction. These results are obtained using techniques from multi-linear algebra. For our main result, we introduce polynomial transducers and prove that for these, validity of a polynomial invariant can be certified by means of an inductive invariant of polynomial ideals. This allows us to construct two semi-algorithms, one searching for a certificate of the invariant and one searching for a witness of its violation. Via a translation into polynomial transducers, we thus obtain that equivalence of general
y
dt
transducers is decidable. In fact, our translation also shows that equivalence is decidable when the output is not in a free monoid but in a free group.
Structure and Function of the 26S Proteasome
Authors: Bard Jared A.M. , Goodall Ellen A. , Greene Eric R. , Jonsson Erik , Dong Ken C. , Martin Andreas
Published: April 2018

As the endpoint for the ubiquitin-proteasome system, the 26S proteasome is the principal proteolytic machine responsible for regulated protein degradation in eukaryotic cells. The proteasome's cellular functions range from general protein homeostasis and stress response to the control of vital processes such as cell division and signal transduction. To reliably process all the proteins presented to it in the complex cellular environment, the proteasome must combine high promiscuity with exceptional substrate selectivity. Recent structural and biochemical studies have shed new light on the many steps involved in proteasomal substrate processing, including recognition, deubiquitination, and ATP-driven translocation and unfolding. In addition, these studies revealed a complex conformational landscape that ensures proper substrate selection before the proteasome commits to processive degradation. These advances in our understanding of the proteasome's intricate machinery set the stage for future studies on how the proteasome functions as a major regulator of the eukaryotic proteome.
The Plausibility of Obesity Paradox in Cancer—Point
Authors: Park Yikyung , Peterson Lindsay L. , Colditz Graham A.
Published: April 2018

In contrast to the convincing evidence that obesity (measured by body mass index, BMI) increases the risk of many different types of cancer, there is an ambiguity in the role of obesity in survival among cancer patients. Some studies suggested that higher BMI decreased mortality risk in cancer patients, a phenomenon called the obesity paradox. The spurious positive association between BMI and cancer survival is likely to be explained by several methodologic limitations including confounding, reverse causation, and collider stratification bias. Also, the inadequacy of BMI as a measure of body fatness in cancer patients commonly experiencing changes in body weight and body composition may have resulted in the paradox. Other factors contributing to the divergent results in literature are significant heterogeneity in study design and method (e.g., study population, follow-up length); time of BMI assessment (pre-, peri-, or post-diagnosis); and lack of consideration for variability in the strength and directions of associations by age, sex, race/ethnicity, and cancer subtype. Robust but practical methods to accurately assess body fatness and body compositions and weight trajectories in cancer survivors are needed to advance this emerging field and to develop weight guidelines to improve both the length and the quality of cancer survival. Cancer Res; 78(8); 1898–903. ©2018 AACR.
Antibody-Dependent Cellular Phagocytosis by Macrophages is a Novel Mechanism of Action of Elotuzumab
Authors: Kurdi Ahmed T. , Glavey Siobhan V. , Bezman Natalie A. , Jhatakia Amy , Guerriero Jennifer L. , Manier Salomon , Moschetta Michele , Mishima Yuji , Roccaro Aldo , Detappe Alexandre , Liu Chia-Jen , Sacco Antonio , Huynh Daisy , Tai Yu-Tzu , Robbins Michael D. , Azzi Jamil , Ghobrial Irene M.
Published: April 2018

Elotuzumab, a recently approved antibody for the treatment of multiple myeloma, has been shown to stimulate Fcγ receptor (FcγR)-mediated antibody-dependent cellular cytotoxicity by natural killer (NK) cells toward myeloma cells. The modulatory effects of elotuzumab on other effector cells in the tumor microenvironment, however, has not been fully explored. Antibody-dependent cellular phagocytosis (ADCP) is a mechanism by which macrophages contribute to antitumor potency of monoclonal antibodies. Herein, we studied the NK cell independent effect of elotuzumab on tumor-associated macrophages using a xenograft tumor model deficient in NK and adaptive immune cells. We demonstrate significant antitumor efficacy of single-agent elotuzumab in immunocompromised xenograft models of multiple myeloma, which is in part mediated by Fc–FcγR interaction of elotuzumab with macrophages. Elotuzumab is shown in this study to induce phenotypic activation of macrophages in vivo and mediates ADCP of myeloma cells though a FcγR-dependent manner in vitro. Together, these findings propose a novel immune-mediated mechanism by which elotuzumab exerts anti-myeloma activity and helps to provide rationale for combination therapies that can enhance macrophage activity. Mol Cancer Ther; 17(7); 1454–63. ©2018 AACR.
Mechanistic Investigations of Diarrhea Toxicity Induced by Anti-HER2/3 Combination Therapy
Authors: Moisan Annie , Michielin Francesca , Jacob Wolfgang , Kronenberg Sven , Wilson Sabine , Avignon Blandine , Gérard Régine , Benmansour Fethallah , McIntyre Christine , Meneses-Lorente Georgina , Hasmann Max , Schneeweiss Andreas , Weisser Martin , Adessi Céline
Published: April 2018

Combination of targeted therapies is expected to provide superior efficacy in the treatment of cancer either by enhanced antitumor activity or by preventing or delaying the development of resistance. Common challenges in developing combination therapies include the potential of additive and aggravated toxicities associated with pharmacologically related adverse effects. We have recently reported that combination of anti-HER2 and anti-HER3 antibodies, pertuzumab and lumretuzumab, along with paclitaxel chemotherapy in metastatic breast cancer, resulted in a high incidence of diarrhea that ultimately limited further clinical development of this combination. Here, we further dissected the diarrhea profile of the various patient dose cohorts and carried out in vitro investigations in human colon cell lines and explants to decipher the contribution and the mechanism of anti-HER2/3 therapeutic antibodies to intestinal epithelium malfunction. Our clinical investigations in patients revealed that while dose reduction of lumretuzumab, omission of pertuzumab loading dose, and introduction of a prophylactic antidiarrheal treatment reduced most severe adverse events, patients still suffered from persistent diarrhea during the treatment. Our in vitro investigations showed that pertuzumab and lumretuzumab combination treatment resulted in upregulation of chloride channel activity without indication of intestinal barrier disruption. Overall, our findings provide a mechanistic rationale to explore alternative of conventional antigut motility using medication targeting chloride channel activity to mitigate diarrhea of HER combination therapies. Mol Cancer Ther; 17(7); 1464–74. ©2018 AACR.
Cronkhite-Canada Syndrome Associated with Metastatic Colon Cancer
Authors: Haghighi Shirin , Noorali Sima , Mohammad Alizadeh Amir Houshang
Published: April 2018

Cronkhite-Canada syndrome is characterized by gastrointestinal and ectodermal manifestations. In this paper, we describe a 64-year-old Iranian male, presenting with Cronkhite-Canada syndrome with metastatic colon cancer. The patient was suffering from hair loss, which occurred on the scalp at first and then, during 5 months, extended to the whole body. After that, his sense of taste was impaired, and 2 months later, gastrointestinal symptoms gradually started, with weight loss of 20 kg over 2 months with an initial weight of 100 kg. Finally, he was admitted to our center 10 months after the onset of symptoms. On skin examination, generalized hair loss and hyperpigmentation and dysmorphic nail changes were observed. Multiple polyps within the colon and sigmoid were observed on colonoscopy. According to biopsies, a serrated adenoma and an invasive adenocarcinoma were reported in the ascending colon and sigmoid, respectively. Other polyps were pseudopolyps, and their characteristics were not significant. Computed tomography of the lungs and abdomen showed multiple adenopathies. On biopsy, metastatic adenocarcinoma was reported. The patient underwent chemotherapy with FOLFIRI and ERBITUX. Finally, after 5 courses of chemotherapy, his regimen was changed to FOLFOX and Avastin because of evidence of progression on computed tomography. The etiology of Cronkhite-Canada syndrome is currently unknown, and the optimal therapy has not been reported so far. This syndrome has many complications; the major of them is malignancy, and the prognosis is poor with a mortality rate of 50%. Therefore, annual monitoring is necessary in these patients.
Intrapopulation Chromosomal Polymorphism in Mazama gouazoubira (Cetartiodactyla; Cervidae): The Emergence of a New Species?
Authors: Valeri Mirela P. , Tomazella Iara M. , Duarte José M.B.
Published: April 2018

Mazama gouazoubira is a small deer species widely distributed in South America. Previous studies have shown that this species presents intraspecific chromosomal polymorphisms, which could affect fertility due to the effects of chromosomal rearrangements on gamete formation. Important aspects regarding the karyotype evolution of this species and the genus remain undefined due to the lack of information concerning the causes of this chromosomal variation. Nineteen individuals belonging to the Mazama gouazoubira population located in the Pantanal were cytogenetically evaluated. Among the individuals analyzed, 9 had B chromosomes and 5 carried a heterozygous centric fusion (2n = 69 and FN = 70). In 3 individuals, the fusion occurred between chromosomes X and 16, in 1 individual between chromosomes 7 and 21, and in another individual between chromosomes 4 and 16. These striking polymorphisms could be explained by several hypotheses. One is that the chromosome rearrangements in this species are recent and not fixed in the population yet, and another hypothesis is that they represent a balanced polymorphism and that heterozygotes have an adaptive advantage. On the other hand, these polymorphisms may negatively influence fertility and raise questions about sustainability or reproductive isolation of the population.
Sociocultural and Familial Factors Associated with Weight Bias Internalization
Authors: Pearl Rebecca L. , Wadden Thomas A. , Shaw Tronieri Jena , Chao Ariana M. , Alamuddin Naji , Bakizada Zayna M. , Pinkasavage Emilie , Berkowitz Robert I.
Published: April 2018

Background/Aims: Sociocultural and familial factors associated with weight bias internalization (WBI) are currently unknown. The present study explored the relationship between interpersonal sources of weight stigma, family weight history, and WBI. Methods: Participants with obesity (N = 178, 87.6% female, 71.3% black) completed questionnaires that assessed the frequency with which they experienced weight stigma from various interpersonal sources. Participants also reported the weight status of their family members and completed measures of WBI, depression, and demographics. Participant height and weight were measured to calculate body mass index (BMI). Results: Linear regression results (controlling for demographics, BMI, and depression) showed that stigmatizing experiences from family and work predicted greater WBI. Experiencing weight stigma at work was associated with WBI above and beyond the effects of other sources of stigma. Participants who reported higher BMIs for their mothers had lower levels of WBI. Conclusion: Experiencing weight stigma from family and at work may heighten WBI, while having a mother with a higher BMI may be a protective factor against WBI. Prospective research is needed to understand WBI's developmental course and identify mechanisms that increase or mitigate its risk.
Materiais pictóricos da cerâmica Guarani do alto Uruguai a partir de medidas de fluorescência de raios X
Authors: Carbonera Mirian , Appoloni Carlos R. , Santos Gustavo H. dos
Published: April 2018

Os Guarani pré-coloniais estavam distribuídos por grandes áreas da América do Sul, especialmente em regiões da Bacia do Rio da Prata e zonas litorâneas do Sul do Brasil. A grande característica em termos de cultura material é sua produção cerâmica, com destaque para os vasilhames pintados tanto na superfície externa como na interna. Apresentamos, a partir de medidas de fluorescência de raios X, a análise dos dados de proveniência dos pigmentos utilizados na produção das tintas aplicadas no acabamento de cerâmicas da unidade Guarani de três sítios arqueológicos localizados na Volta do Uvá, alto rio Uruguai. Esta análise indicou que os pigmentos vermelho e branco provêm de materiais inorgânicos derivados de minerais terrosos.
Firing temperature determination and thermoluminescence dating of a brick with cuneiform characters found in the ruins of Ancient Babylon
Authors: Silva Rodrigo P. da , Tudela Diego R.G. , Munita Casimiro S. , Hazenfratz Roberto , Tatumi Sonia H. , Yee Marcio , Mittani Juan C.R.
Published: April 2018

Este artigo tem por objetivo estudar um tijolo com inscrições em caracteres cuneiformes cujas sentenças estão praticamente completas. Estudos tipológicos correspondentes aos relatos históricos sugerem que o tijolo foi manufaturado no século VI a.C., durante a dinastia de Nabucodonosor II, grande monarca da Babilônia. A amostra foi estudada através da difração de raios X (DRX), ressonância paramagnética de elétron (RPE), termoluminescência (TL) e técnicas de análise por ativação instrumental com nêutrons (AAIN). Os resultados demonstraram que o tijolo tem 2350 anos de idade (± 40) e queima menor que 400o C.
Imaging Insights on the Aorta in Aging
Authors: Ohyama Yoshiaki , Redheuil Alban , Kachenoura Nadjia , Ambale Venkatesh Bharath , Lima Joao A.C.
Published: April 2018

The aorta has 2 main functions, conduit and cushion, and is designed to transmit blood to the periphery and buffer pulsatile stress from ventricular contraction. In the interaction between the structural and functional changes of the aorta, aging and disease processes impact on aortic material properties and hemodynamics. For a comprehensive assessment of changes in aortic structure and function associated with aging and disease, noninvasive cardiovascular imaging techniques, especially magnetic resonance imaging, have recently been developed. Magnetic resonance imaging allows for direct and accurate measurement of different aortic characteristics including structural measures such as aortic area or volume, aortic length, curvature, and aortic wall thickness and functional measures such as aortic strain, distensibility, and pulse wave velocity. Excellent reproducibility of magnetic resonance imaging methods allows us to assess the response of the whole aorta to both pharmacological and nonpharmacological therapies. Aortic flow and functional assessment could be added to clinical routine cardiac magnetic resonance as a comprehensive imaging modality primarily performed for the noninvasive evaluation of left ventricular function, left ventricular load, and vascular/ventricular coupling. New techniques such as 4-dimensional flow could provide and further elucidate the combined age-related effects of altered aortic geometry and function. This following review will describe the pathophysiological aspects of the aorta and the ability, value, and prospects of cardiovascular imaging, especially magnetic resonance imaging, to study age-related changes in aortic structure and function and assess the relationship between these alterations and cardiovascular disease.
Association Between Early Outpatient Visits and Readmissions After Ischemic Stroke
Authors: Terman Samuel W. , Reeves Mathew J. , Skolarus Lesli E. , Burke James F.
Published: April 2018

Background:

Reducing hospital readmission is an important goal to optimize poststroke care and reduce costs. Early outpatient follow-up may represent one important strategy to reduce readmissions. We examined the association between time to first outpatient contact and readmission to inform postdischarge transitions.

Methods and Results:

We performed a retrospective cohort study of all Medicare fee-for-service patients discharged home after an acute ischemic stroke in 2012 identified by the
InternationalClassification of Diseases, Ninth Revision, Clinical Modification
codes. Our primary predictor variable was whether patients had a primary care or neurology visit within 30 days of discharge. Our primary outcome variable was all-cause 30-day hospital readmission. We used separate multivariable Cox models with primary care and neurology visits specified as time-dependent covariates, adjusted for numerous patient- and systems-level factors. The cohort included 78 345 patients. Sixty-one percent and 16% of patients, respectively, had a primary care and neurology visit within 30 days of discharge. Visits occurred a median (interquartile range) 7 (4–13) and 15 (5–22) days after discharge for primary care and neurology, respectively. Thirty-day readmission occurred in 9.4% of patients. Readmissions occurred a median 14 (interquartile range, 7–21) days after discharge. Patients who had a primary care visit within 30 days of discharge had a slightly lower adjusted hazard of readmission than those who did not (hazard ratio, 0.98; 95% confidence interval, 0.97–0.98). The association was nearly identical for 30-day neurology visits (hazard ratio, 0.98; 95% confidence interval, 0.97–0.98).

Conclusions:

Thirty-day outpatient follow-up was associated with a small reduction in hospital readmission among elderly patients with stroke discharged home. Further work should assess how outpatient care may be improved to further reduce readmissions.
Value-Based ST-Segment–Elevation Myocardial Infarction Care Using Risk-Guided Triage and Early Discharge
Authors: Ebinger Joseph E. , Strauss Craig E. , Garberich Ross R. , Bradley Steven M. , Rush Pam , Chavez Ivan J. , Poulose Anil K. , Porten Brandon R. , Henry Timothy D.
Published: April 2018

Background:

Prior studies suggest that low-risk ST-segment–elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention can be considered for early discharge. We describe the implementation of an STEMI risk score to decrease cost while maintaining optimal patient outcomes.

Methods and Results:

We determined the impact of risk-guided STEMI care on healthcare value through the retrospective application of the Zwolle Risk Score to 967 patients receiving primary percutaneous coronary intervention between 2009 and 2011. Of these patients, 540 (56%) were categorized as low risk, indicating they may be safely triaged directly to a telemetry unit rather than the intensive care unit and targeted for early discharge. We subsequently developed and implemented a modified Zwolle Risk Calculator into the electronic medical record to support application of the fast-track protocol for low-risk STEMI patients. Among 549 prospective patients with STEMI, 62% were low risk, and the fast-track protocol was followed in 75% of cases. Prospective results confirmed lower rates of complications (low risk 8.3% versus high risk 38.7%;
P
<0.001) and in-hospital mortality (low risk 0.4% versus High risk 12.5%;
P
<0.001) in the low-risk cohort. Low-risk patients had a shorter median length of stay (median and [25th, 75th percentiles]: low risk 2 [2, 3] versus high risk: 3 [2, 6];
P
<0.001) and lower overall costs (low risk $6720 [$5280–$9030] versus high risk $11 783 [$7953–$25 359];
P
<0.001). Low-risk patients treated on-protocol had shorter median length of stay (on-protocol 2 [1, 2] versus off-protocol 2 [2, 3];
P
<0.001) and hospital costs (on-protocol $6090 [$4730, $7356] versus off-protocol $11 783 [$7953, $25 359];
P
<0.001) than those treated off-protocol. On-protocol low-risk patients in the prospective cohort also had lower costs and shorter length of stay than low-risk patients in the retrospective cohort (
P
<0.001 for both).

Conclusions:

In our study, risk-guided triage and discharge after primary percutaneous coronary intervention for STEMI improved healthcare value by reducing costs of care without compromising quality of care or patient outcomes.
Mineralocorticoid Receptor Antagonism in Patients With Atrial Fibrillation: Findings From the ORBIT‐AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) Registry
Authors: Fudim Marat , Liu Peter R. , Shrader Peter , Blanco Rosalia G. , Allen Larry A. , Fonarow Gregg C. , Gersh Bernard J. , Kowey Peter R. , Mahaffey Kenneth W. , Hylek Elaine , Go Alan S. , Thomas Laine , Peterson Eric D. , Piccini Jonathan P.
Published: April 2018

Background

Mineralocorticoid receptor antagonist (
MRA
) therapy may be beneficial to patients with atrial fibrillation (
AF
), but little is known about their use in patients with
AF
and subsequent outcomes.

Methods and Results

In order to better understand
MRA
use and subsequent outcomes, we performed a retrospective cohort study of the contemporary
ORBIT
‐
AF
(Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) registry.
AF
progression and cardiovascular outcomes were compared using propensity‐matched Cox proportional hazards modeling according to
MRA
use at baseline and new
MRA
use at follow‐up versus patients with no
MRA
use. Among 7012 patients with nonpermanent
AF
, 320 patients were taking
MRA
at enrollment, and 416 patients initiated
MRA
use during follow‐up. The mean patient age was 72.5 years, 56.3% were men, and 70.4% had paroxysmal
AF
. Among all patients taking
MRAs,
434 (59.0%) had heart failure, 655 (89.0%) had hypertension, and 380 (51.6%) had both. After adjustment, new
MRA
use was not associated with reduced
AF
progression (hazard ratio, 1.18; 95% confidence interval, 0.88–1.58;
P
=0.27) but showed a trend towards lower risk of stroke, transient ischemic attack, or systemic embolism (hazard ratio, 0.17; 95% confidence interval, 0.02–1.23;
P
=0.08). Results were similar for a comparison of new
MRA
users and baseline
MRA
users compared with nonusers.

Conclusions

In community‐based outpatients with
AF
, the majority of
MRA
use was for
heart failure
and hypertension.
MRA
use also trended towards lower adjusted stroke risk. Future studies should test the hypothesis that
MRA
use may decrease the risk of stroke in patients with
AF
.