bluuebunny/crossref_metadata_2025 huggingface dataset:
Toward Inclusive Trial Protocols in Heterogeneous Neurological Disorders
Authors: Tanadini Lorenzo G. , Hothorn Torsten , Jones Linda A. T. , Lammertse Daniel P. , Abel Rainer , Maier Doris , Rupp Rüdiger , Weidner Norbert , Curt Armin , Steeves John D.
Published: February 2015

Background. Several novel drug- and cell-based potential therapies for spinal cord injury (SCI) have either been applied or will be considered for future clinical trials. Limitations on the number of eligible patients require trials be undertaken in a highly efficient and effective manner. However, this is particularly challenging when people living with incomplete SCI (iSCI) represent a very heterogeneous population in terms of recovery patterns and can improve spontaneously over the first year after injury. Objective. The current study addresses 2 requirements for designing SCI trials: first, enrollment of as many eligible participants as possible; second, refined stratification of participants into homogeneous cohorts from a heterogeneous iSCI population. Methods. This is a retrospective, longitudinal analysis of prospectively collected SCI data from the European Multicenter study about Spinal Cord Injury (EMSCI). We applied conditional inference trees to provide a prediction-based stratification algorithm that could be used to generate decision rules for the appropriate inclusion of iSCI participants to a trial. Results. Based on baseline clinical assessments and a defined subsequent clinical endpoint, conditional inference trees partitioned iSCI participants into more homogeneous groups with regard to the illustrative endpoint, upper extremity motor score. Assuming a continuous endpoint, the conditional inference tree was validated both internally as well as externally, providing stable and generalizable results. Conclusion. The application of conditional inference trees is feasible for iSCI participants and provides easily implementable, prediction-based decision rules for inclusion and stratification. This algorithm could be utilized to model various trial endpoints and outcome thresholds.
Which type of conditioning method protects the spinal cord from the ischemia–reperfusion injury in 24 hours?
Authors: Sapmaz Ali , Ulus A Tulga , Turan Nilüfer N , Kaymaz F Figen , Yazıcıoğlu Hija , Ersöz Siyar , Simsek Erdal , Köksoy Cüneyt
Published: February 2015

Objective

This study was designed to test the effects of different types of preconditioning and postconditioning methods on spinal cord protection following aortic clamping.

Methods

The animals (rabbits) were divided into sham-operated, ischemic preconditioning, remote ischemic preconditioning, simultaneous aortic and ischemic remote preconditioning, and ischemic postconditioning groups. After neurological evaluations, ultrastructural analysis and immunohistochemical staining for caspase-3 were evaluated after 24 h following ischemia.

Results

The neurological outcomes of the remote ischemic preconditioning (4.2 ± 0.4) and ischemic postconditioning (4.6 ± 0.8) groups were significantly improved when compared with the ischemia group (2.2 ± 04). The immunohistochemical analysis revealed that the lowest percentage of apoptosis was in-group ischemic preconditioning at 12.5 ± 30.6%. In the comparison of intracellular edema in an ultrastructural analysis, the ischemic preconditioning and ischemic postconditioning groups had significantly lower values than the ischemia group.

Conclusion

The conditioning methods attenuate ischemia–reperfusion injury for spinal cord injury. Ischemic and remote preconditioning and also postconditioning methods are simple to perform and inexpensive.
Outreach to diversify clinical trial participation: A randomized recruitment study
Authors: Brown Susan D , Partee Paula N , Feng Juanran , Quesenberry Charles P , Hedderson Monique M , Ehrlich Samantha F , Kiernan Michaela , Ferrara Assiamira
Published: February 2015

Background/Aims

Racial and ethnic minorities remain underrepresented in clinical research, yet few recruitment strategies have been rigorously evaluated.

Methods

We experimentally tested whether targeted recruitment letters acknowledging diabetes health disparities and health risks specific to recipients’ racial/ethnic group improved two metrics of trial participation: willingness to be screened and enrollment. This experiment was efficiently nested within a randomized clinical trial examining a preventive lifestyle intervention among women at high risk for diabetes. Pregnant women with gestational diabetes or impaired glucose tolerance ( N = 445) were randomized to receive a targeted recruitment letter with health risk information specific to their racial/ethnic group ( n = 216), or a standard letter with risk information for the general population ( n = 229). All letters were bilingual in English and Spanish.

Results

The targeted as compared to the standard letter did not improve screening or enrollment rates overall or within separate racial/ethnic groups. Among Latina women who preferred Spanish, the targeted letter showed trends for improved screening (66.7% vs 33.3%, p = .06) and enrollment rates (38.9% vs 13.3%, p = .13). In contrast, among Latina women who preferred English, the targeted letter significantly lowered screening (29.6% vs 57.1%, p = .04) and showed trends for lowered enrollment rates (25.9% vs 50.0%, p = .07).

Conclusion

Results from this randomized study appear to suggest that recruitment letters with diabetes health risk information targeted to recipients’ race/ethnicity may improve one metric of clinical trial participation among Latina women who prefer Spanish, but not English. Larger experimental studies, incorporating input from diverse participant stakeholders, are needed to develop evidence-based minority recruitment strategies.
On discharge planning: dynamic complex processes – uncertainty, surprise and standardisation
Authors: Augustinsson Sören , Petersson Pia
Published: February 2015

How can discharge planning (DP) for patients who require care in the home following a period in hospital be understood and developed through the lenses of complexity theory? With the help of complexity theory and practice-based narrative research this study discloses the formal routines and complex dynamic practices that are associated with DP. A study of the literature established that there was an almost total absence of complexity-theoretical perspectives on interpreting and developing DP.

The researchers collected narratives about the DP processes using qualitative interviews with the nurses responsible for this in a hospital ward: these were audio-recorded and transcribed verbatim. They also participated in and documented meetings where these nurses, as a group, discussed DP.

The findings show that nurses have to continuously deal with uncertainty, surprises and the unknown. They have to make sense and take charge of dynamic complex events and new knowledge, and manage complex relations and information. The researchers argue that looking upon practice from the lenses of complexity theory, and therefore accepting the complexity of practice, could facilitate the development of nurses' skills in order to guarantee good quality in DP.
Crafting intermediate care: one team’s journey towards integration and innovation
Authors: Fillmore Elbourne Heather , le May Andrée
Published: February 2015

Aim

This paper describes one multi-disciplinary, multi-agency team’s development of Person-Centred Intermediate Care (PCIC) for older people. This development involved integrating three separate enterprises – a not-for-profit charitable organisation, a local primary health care trust and referring hospitals and their local social care providers.

Methods

We used a mixed-methods case study, underpinned by the notion of an innovation journey, to explore how PCIC was developed by the team and how effective it was. Data were collected through semi-structured interviews, documentary analysis, closed-end questionnaires/scales and routinely collected activity data. Thematic and statistical analyses were used. Results were triangulated. Twelve staff, four key informants and 94 service users participated.

Results

The development followed the trajectory of innovation journeys. Our mixed-methods approach enabled us to expose staff’s negative experiences during this time whilst patients were largely satisfied with their care and made appropriate recovery. The triangulation of data in this mixed-methods study allowed us to seek explanations for this mismatch. We conjecture that the staff used emotional labour to lessen the effects of their negative experiences for the benefit of the patients.

Conclusions

This paper extends our knowledge of how, in a policy environment that encourages collaborative practice between public, private and voluntary alliances, and across sectors, such innovations work. In addition, the results suggest that emotional labour is used during change and care practices: preparing nurses better in order to use this ‘technique’ is a recommendation from this research.
Satirical cultures of media publics in Iran
Authors: Rahimi Babak
Published: February 2015

The article discusses the relationship between political satire and changing media practices in the context of Iranian political history. It argues how such practices produce distinct forms of publics with mediated modes of expression of dissent. From print to the Internet, media technologies have enabled different forms of communication that, correspondingly, have led to the formation of different form of satirical publics of (sub)cultural variations. First, the study offers an account of political satire in its print cultural form and, second, its reconfiguration with the introduction of the Internet to Iran in the 1990s. With the Internet, I further identify three satirical practices: (a) prose, (b) cartoon, (c) and meme, with the last introducing a new form of satirical practice as a result of interactive communication in social media. The article finally discusses limits to studying political satire, especially in Iran, and argues that the impact of political satire on politics remains to be seen.
Healthcare costs and loss of productivity in patients with trapeziometacarpal osteoarthritis
Authors: Marks M. , Vliet Vlieland T. P. M. , Audigé L. , Herren D. B. , Nelissen R. G. H. H. , van den Hout W. B.
Published: February 2015

The objective of this study was to analyse healthcare and productivity costs in patients with trapeziometacarpal osteoarthritis. We included 161 patients who received surgery or steroid injection and calculated their healthcare costs in Euro (€) over 1 year. Patients filled out the Work Productivity and Activity Impairment Questionnaire to assess loss of productivity at baseline, and after 3, and 12 months. In the surgical group, loss of productivity among employed patients first increased and then decreased (50%, 64%, and 25% at 0, 3, and 12 months). Productivity was more stable over time in the injection group (52%, 38%, and 48%). In the surgical group, estimated total annual healthcare and productivity costs were €5770 and €5548, respectively. In the injection group, healthcare and productivity costs were €348 and €3503. These findings highlight the need for assessing productivity costs to get a comprehensive view of the costs associated with a treatment.

Level of Evidence III
Corrective osteotomy for malunited metacarpal fractures: long-term results of a novel technique
Authors: Karthik K. , Tahmassebi R. , Khakha R. S. , Compson J.
Published: February 2015

Symptomatic malunited metacarpal fractures can significantly affect hand function. We retrospectively reviewed the results of our technique of corrective osteotomy in 14 malunited metacarpal fractures (12 patients) with an average age of 30 years (range 18–49) from January 2005 to December 2011. The dominant hand was involved in nine patients and all except one were male. The malunited metacarpals demonstrated mean dorsal apex angulation of 43° (range 33°–72°) with apparent metacarpal shortening. All except three cases had rotational deformity. All patients underwent surgical correction of the deformity using our described technique of closing wedge osteotomy using temporary intramedullary K-wire and plate fixation. At a mean follow-up of 46 months (range 12–78), the DASH scores improved significantly ( p < 0.001). All our patients scored ‘excellent’ according to the Büchler criteria and at final follow-up had returned to pre-injury work and sports activities. Our technique is safe, easily performed and can be adapted to correct a range of deformities.

Level of evidence: Level IV
Allergies and the skin
Authors: Mishra Apurva
Published: February 2015

It is common in primary care to see people presenting with symptoms secondary to allergy, which could range from minor rashes or rhinitis to life-threatening anaphylaxis. The skin is the largest human organ, and it is involved in allergy; through both direct exposure to the allergens and manifestations of the allergic reaction. The aim of this article is to improve understanding of skin allergy and provide an outline on how to investigate and manage allergic skin conditions.
Non-steroidal anti-inflammatory drugs: panacea or poison?
Authors: Pope Charlie A , Spacie Robin , Mackintosh Will
Published: February 2015

Non-steroidal anti-inflammatory drugs (NSAIDs) form an integral part of the World Health Organization’s (WHO's) pain ladder and in 2012 over 4 500 000 prescriptions for ibuprofen were dispensed in England alone. However, several NSAIDs have now been withdrawn from the market due to concerns about cardiovascular risk. Given their widespread use, but well-documented serious side effects, what exactly are NSAIDs, when should they be used, and how can the risk to your patients be minimised?
Femorofemoral bypass allowed limb preservation after late diagnosis of left common iliac artery thrombosis due to blunt trauma: A case report
Authors: Chen Kai , Huang Jing-Yong , Wang Lu , Zheng Xiang-Tao
Published: February 2015

Objective:

Acute common iliac artery occlusion which results from blunt abdominal trauma is rare and potentially leads to a late diagnosis.

Methods:

We report a case of a 58-year-old patient who suffered a late diagnosed acute left common iliac artery occlusion secondary to abdominal trauma. An emergency exploratory laparotomy was performed to stop intra-abdominal bleeding, while his left limb ischemia was not noticed until 32 h later and femorofemoral bypass was then successfully performed for revascularization. Compartment syndrome was observed postoperatively, and fasciotomy was performed promptly. The wound was temporarily covered with Vaccum Sealing Drainage due to high skin tension. Patient underwent skin-grafting after leg swelling subsided.

Results:

The follow-up turned out that these managements were valid in the preservation of the limb viability.

Conclusions:

This case highlights the prudent recognition of the acute lower extremity ischemia in the abdominal trauma and immediate remedy for acute iliac artery occlusion after a late diagnosis.
Flourishing
Authors: Kading Margarette L. , Hautala Dane S. , Palombi Laura C. , Aronson Benjamin D. , Smith Reid C. , Walls Melissa L.
Published: February 2015

Positive mental health (PMH) is an important construct for understanding the full continuum of mental health. Some socially disadvantaged populations experience a paradoxically high level of PMH despite negative social experiences including discrimination. The purpose of this study is to examine the prevalence and culturally salient correlates of PMH among a cross-sectional sample of 218 American Indian adults living with type 2 diabetes mellitus. Although 17.1 percent of individuals in this sample met Patient Health Questionnaire (PHQ-9) criteria for depression, 51.5 percent were in flourishing PMH. Perceived discrimination was negatively associated with PMH, and participation in traditional cultural activities was positively associated with PMH. Traditional cultural activities did not appear to buffer the impact of discrimination on PMH. This study contributes to strengths-based research with American Indian communities, furthers our understanding of correlates of PMH, and documents comparatively high rates of flourishing mental health in our sample relative to previously published studies with diverse samples.
Ovarian Torsion With Persistent Parenchymal Blood Flow
Authors: Desmond Marianna , Baun Jim
Published: February 2015

Ovarian torsion is the complete or partial rotation of the ovary upon its vascular pedicle with subsequent vascular compromise; it is one of a few gynecologic surgical emergencies requiring prompt diagnosis and treatment. The commonly accepted diagnostic sonographic finding in ovarian torsion is the absence of ovarian parenchymal blood flow using color or power Doppler imaging. However, since not all cases of ovarian torsion cause complete vascular obstruction, the presence of ovarian blood flow cannot eliminate this diagnosis in symptomatic patients with other positive sonographic findings. The case presented demonstrates the potential for a missed diagnosis of ovarian torsion when relying predominantly on Doppler findings.
Minimal residual disease in myeloma by flow cytometry: independent prediction of survival benefit per log reduction
Authors: Rawstron Andy C. , Gregory Walter M. , de Tute Ruth M. , Davies Faith E. , Bell Sue E. , Drayson Mark T. , Cook Gordon , Jackson Graham H. , Morgan Gareth J. , Child J. Anthony , Owen Roger G.
Published: February 2015

Key Points

The level of MRD quantified by flow cytometry is more informative than a 0.01% threshold and independently predicts OS. There was approximately 1 year survival benefit per log depletion. A lower cut point for predicting improved outcome was not reached.
Linking a research register to clinical records in older adults’ mental health services: a mixed-methods study
Authors: Robotham Dan , Evans Joanne , Watson Andrew , Perdue Iain , Craig Thomas , Rose Diana , Wykes Til
Published: February 2015

Introduction

Patients can provide consent to have their clinical records linked to a research register, a process known as consent for contact (C4C). There is evidence about how to engage people with mental illness in C4C, but nothing specific to older adults. This is a priority area for research (for example, dementia trials), although sign-up rates to C4C are lower than for younger populations. Through this study we seek to understand these disparities.

Methods

This was a two-stage cross-sectional observational study. In phase one, focus groups with service users, carers and clinicians informed a framework for clinicians to explain C4C to those on their caseload. In phase two, clinicians explained C4C to 26 service users (and carers where applicable). These conversations were recorded, and their content was analysed. Service users and carers were then interviewed to provide further feedback on their conversations with clinicians. A total of 31 service users, 24 carers and 13 clinical staff took part across the two phases.

Results

In phase one, service users and carers sought assurance of the right to refuse participation in further studies (after joining C4C). Clinicians expressed concerns over legal and practical implications of ascertaining mental capacity and best interest. In phase two, clinicians’ explanations were less thorough than similar explanations given to younger adults with psychosis. Clinicians omitted details of service users’ right to stipulate contact arrangements, which was significantly associated with whether service users/carers agreed to join. Common reasons for joining C4C included altruism and the chance to speak to new people. Few participants refused to join, but reasons included avoidance of stress (potentially alleviated through the presence of a carer).

Conclusions

Implementing C4C in older adults’ services requires clinicians to deliver concise, simple explanations to individuals and their carers where applicable. Older adults can be suspicious of unsolicited contact; thus, explanations must emphasise freedom to negotiate suitable contact arrangements. Hearing about research opportunities can be in the best interests of older adults, but communicating these opportunities requires a tailored approach.
Clinical similarities among bradykinin‐mediated and mast cell‐mediated subtypes of non‐hereditary angioedema: a retrospective study
Authors: Schulkes Karlijn J G , Van den Elzen Mignon T , Hack Erik C , Otten Henderikus G , Bruijnzeel‐Koomen Carla A F M , Knulst André C
Published: February 2015

Background

Non‐hereditary angioedema (non‐HAE) is characterized by local swelling due to self‐limiting, subcutaneous or submucosal extravasation of fluid, and can be divided into three subtypes. These subtypes are believed to have different pathophysiological backgrounds and are referred to in recent guidelines as bradykinin‐mediated (e.g. caused by angiotensin‐converting‐enzyme‐inhibitors), mast cell‐mediated (e.g. angioedema with wheals) or idiopathic (cause unknown). Bradykinin‐mediated subtypes are more closely related to hereditary angioedema than the other forms. Because clinical features of these non‐HAE subtypes have not been studied in detail, we have looked at the clinical characteristics of symptoms and potential differences in clinical presentation of bradykinin‐mediated and mast cell‐mediated angioedema (AE) subtypes.

Methods

A questionnaire was sent to patients presenting with AE at our tertiary outpatient clinic to document clinical characteristics, potential triggers and location of AE. The severity of AE attacks was analysed using visual analogue scales (VAS).

Results

The questionnaire was returned by 106 patients, of which 104 were included in the analysis. AE with wheals, idiopathic AE, and drug‐associated AE occurred in 64 (62%), 25 (24%) and 15 patients (14%) respectively. Most patients (62%) reported prodromal symptoms while 63% reported multiple locations for an attack. Face and oropharynx were the main locations of AE attacks of any subtype while swelling was the symptom most frequently reported as severe. Overall severity of the last attack was indicated as severe by 68% of the patients. There were no differences between the subgroups.

Conclusion

This similarity in clinical presentation raises the possibility that ACEi‐induced, mast cell‐mediated and idiopathic AE share common pathways.
Implementation of hybrid image fusion technique for feature enhancement in medical diagnosis
Authors: Agarwal Jyoti , Bedi Sarabjeet Singh
Published: February 2015

Image fusion is used to enhance the quality of images by combining two images of same scene obtained from different techniques. In medical diagnosis by combining the images obtained by Computed Tomography (CT) scan and Magnetic Resonance Imaging (MRI) we get more information and additional data from fused image. This paper presents a hybrid technique using curvelet and wavelet transform used in medical diagnosis. In this technique the image is segmented into bands using wavelet transform, the segmented image is then fused into sub bands using curvelet transform which breaks the bands into overlapping tiles and efficiently converting the curves in images using straight lines. These tiles are integrated together using inverse wavelet transform to produce a highly informative fused image. Wavelet based fusion extracts spatial details from high resolution bands but its limitation lies in the fusion of curved shapes. Therefore for better information and higher resolution on curved shapes we are blending wavelet transform with curvelet transform as we know that curvelet transform deals effectively with curves areas, corners and profiles. These two fusion techniques are extracted and then fused implementing hybrid image fusion algorithm, findings shows that fused image has minimum errors and present better quality results. The peak signal to noise ratio value for the hybrid method was higher in comparison to that of wavelet and curvelet transform fused images. Also we get improved statistics results in terms of Entropy, Peak signal to noise ratio, correlation coefficient, mutual information and edge association. This shows that the quality of fused image was better in case of hybrid method.
Decentralised combined heat and power in the German Ruhr Valley; assessment of factors blocking uptake and integration
Authors: Viétor Birte , Hoppe Thomas , Clancy Joy
Published: February 2015

Background

In Germany, the energy system is undergoing reorganisation from a centralised system based on fossil fuels and nuclear power to a sustainable system based on decentralised production and consumption of energy, the so-called Energiewende. Recently, there has been more attention to improving energy efficiency in those regions where conventional energy production activities and energy-intensive industries are located, such as the Ruhr area. Although the potential for decentralised combined heat and power (CHP) units is high in this region, local action plans show only modest developments for this technology. In this paper, we address this issue by answering the following research question: Which factors block the uptake and integration of decentralised CHP in the German Ruhr area's energy system?

Methods

The multilevel perspective (MLP) was used to analyse the state of system innovation in relation to the uptake and integration of decentralised CHP technology. Prior to the MLP analysis, a stakeholders' analysis was conducted to identify stakeholders' views, positions and experienced barriers regarding the uptake and integration of decentralised CHP technology. Data collection included review of text documents and conducting 11 interviews.

Results

Due to many regime barriers blocking niche development, the uptake of decentralised CHP technology is limited. Identified barriers relate to lack of market services and mismatches with user preferences, (sectoral) policies and industrial interests.

Conclusions

Observed barriers relate to (i) lack of market services such as financial means for making investments; (ii) user awareness such as unawareness and information deficit regarding the benefits of decentralised CHP to potential users, (iii) the presence of centralised district heating systems, (iv) policy issues such as lack of sufficient policies supporting diffusion of decentralised CHP units, legal stipulations from social housing policies that prevent housing cooperatives from becoming energy producers and district heating systems owned by public and private owners (via concessions contracts); (v) sector issues such as lack of skilled service-providing companies; and (vi) industrial interested such as the vested interests of the coal and gas industry. Moreover, many of the mentioned barriers seem interrelated, especially those concerning policy and finance available for making upfront investments.
Patient-specific simulation of tumor growth, response to the treatment, and relapse of a lung metastasis: a clinical case
Authors: Colin Thierry , Cornelis François , Jouganous Julien , Palussière Jean , Saut Olivier
Published: February 2015

In this paper, a parametrization strategy based on reduced order methods is presented for tumor growth PDE models. This is applied to a new simple spatial model for lung metastasis including angiogenesis. The goal is to help clinicians monitoring tumors and eventually predicting their evolution or response to a particular kind of treatment. To illustrate the whole approach, a clinical case including the natural history of the lesion, the response to a chemotherapy, and the relapse before a radiofrequency ablation is presented.
A survey on pulmonary screening practices among otolaryngology-head & neck surgeons across Canada in the post treatment surveillance of head and neck squamous cell carcinoma
Authors: Madana J , Morand Gregoire B , Barona-Lleo Luz , Black Martin J , Mlynarek Alex M , Hier Michael P
Published: February 2015

Background

Post treatment lung screening for head and neck cancer patients primarily focuses on the distant metastasis and a high rate of second primary can also be expected. The best screening tool and timing for this purpose is controversial. We sought out to assess the current practice and beliefs among Canadian Head and Neck Surgeons.

Methods

After Ethical Board approval, a nationwide survey was conducted through the Canadian Society of Otolaryngology (CSO) among head and neck surgeons regarding their practices for pulmonary screening in HNSCC patients.

Results

Our CSO survey among Otolaryngology-head and neck surgeons showed that 26 out of 32 respondents perform routine lung screen, out of which 23 (88%) feel that chest radiography should be preferred. The majority of respondents felt that lung screening could impact beneficially on mortality. For symptomatic patients, low-dose spiral CT was the preferred modality (48%), followed by PET/CT scan (14%) and sputum cytology (14%). In high-risk asymptomatic patients (current smoker, radiation exposure, family history and advanced HNSCC), 31% of respondents performed a CXR. The same percentage performed a low dose CT, while 19% relied on PET scan. A further 19% of respondents did not perform any screening in high-risk patients. Most respondents (77%) had more than 10 years practice since graduation from medical school and came from the provinces of Quebec, Ontario and Alberta.

Conclusion

Chest radiography remains the preferred modality for lung screening and was believed to be impacting beneficially on lung mortality. The recent literature does not seem to be in agreement with those beliefs. Further studies to establish which modality is best and concurrent nation-wide education are warranted.
SAMHD1’s protein expression profile in humans
Authors: Schmidt Sarah , Schenkova Kristina , Adam Tarek , Erikson Elina , Lehmann-Koch Judith , Sertel Serkan , Verhasselt Bruno , Fackler Oliver T , Lasitschka Felix , Keppler Oliver T
Published: February 2015

The deoxynucleoside triphosphate triphosphohydrolase and 3′ → 5′ exonuclease SAMHD1 restricts HIV-1 infection in noncycling hematopoietic cells in vitro, and SAMHD1 mutations are associated with AGS. Little is known about the in vivo expression and functional regulation of this cellular factor. Here, we first assessed the SAMHD1 protein expression profile on a microarray of 25 human tissues from >210 donors and in purified primary cell populations. In vivo, SAMHD1 was expressed in the majority of nucleated cells of hematopoietic origin, including tissue-resident macrophages, DCs, pDCs, all developmental stages of thymic T cells, monocytes, NK cells, as well as at lower levels in B cells. Of note, SAMHD1 was abundantly expressed in HIV target cells residing in the anogenital mucosa, providing a basis for its evaluation as a cellular factor that may impact the efficiency of HIV transmission. Next, we examined the effect of the activation status and proinflammatory cytokine treatment of cells on expression and phosphorylation of SAMHD1. Activated, HIV-susceptible CD4+ T cells carried pSAMHD1(T592), whereas resting CD4+ T cells and macrophages expressed the unphosphorylated protein with HIV-restrictive activity. Surprisingly, stimulation of these primary cells with IFN-α, IFN-γ, IL-4, IL-6, IL-12, IL-18, IL-27, or TNF-α affected neither SAMHD1 expression levels nor threonine 592 phosphorylation. Only IL-1β moderately down-regulated SAMHD1 in activated CD4+ T cells. Taken together, this study establishes the first cross-sectional protein expression profile of SAMHD1 in human tissues and provides insight into its cell cycle-dependent phosphorylation and unresponsiveness to multiple proinflammatory cytokines.
Editorial: A new checkpoint in the path to GVHD? How bedside-to-bench stem cell transplant studies can inform human GVHD biology
Authors: Barrett Austin John
Published: February 2015

Discussion of how bedside to bench stem cell transplant studies inform human GVHD biology.
Axillary Ultrasound After Neoadjuvant Chemotherapy and Its Impact on Sentinel Lymph Node Surgery: Results From the American College of Surgeons Oncology Group Z1071 Trial (Alliance)
Authors: Boughey Judy C. , Ballman Karla V. , Hunt Kelly K. , McCall Linda M. , Mittendorf Elizabeth A. , Ahrendt Gretchen M. , Wilke Lee G. , Le-Petross Huong T.
Published: February 2015

Purpose

The American College of Surgeons Oncology Group Z1071 trial reported a 12.6% false-negative rate (FNR) for sentinel lymph node (SLN) surgery after neoadjuvant chemotherapy (NAC) in cN1 disease. Patients were not selected for surgery based on response, but a secondary end point was to determine whether axillary ultrasound (AUS) after NAC after fine-needle aspiration cytology can identify abnormal nodes and guide patient selection for SLN surgery.

Patients and Methods

Patients with T0-4, N1-2, M0 breast cancer underwent AUS after neoadjuvant chemotherapy. AUS images were centrally reviewed and classified as normal or suspicious lymph nodes. AUS findings were tested for association with pathologic nodal status and SLN FNR. The impact of AUS results to select patients for SLN surgery to reduce the FNR was assessed.

Results

Postchemotherapy AUS images were reviewed for 611 patients. One hundred thirty (71.8%) of 181 AUS-suspicious patients were node positive at surgery compared with 243 (56.5%) of 430 AUS-normal patients (P < .001). Patients with AUS-suspicious nodes had a greater number of positive nodes and greater metastasis size (P < .001). The SLN FNR was not different based on AUS results; however, using a strategy where only patients with normal AUS undergo SLN surgery would potentially reduce the FNR in Z1071 patients with ≥ two SLNs removed from 12.6% to 9.8% when preoperative AUS results are considered as part of SLN surgery.

Conclusion

AUS is recommended after chemotherapy to guide axillary surgery. An FNR of 9.8% with the combination of AUS and SLN surgery would be acceptable for the adoption of SLN surgery for women with node-positive breast cancer treated with neoadjuvant chemotherapy.
Childhood Cancer Survivor Study Participants' Perceptions and Understanding of the Affordable Care Act
Authors: Park Elyse R. , Kirchhoff Anne C. , Perez Giselle K. , Leisenring Wendy , Weissman Joel S. , Donelan Karen , Mertens Ann C. , Reschovsky James D. , Armstrong Gregory T. , Robison Leslie L. , Franklin Mariel , Hyland Kelly A. , Diller Lisa R. , Recklitis Christopher J. , Kuhlthau Karen A.
Published: February 2015

Purpose

The Patient Protection and Affordable Care Act (ACA) established provisions intended to increase access to affordable health insurance and thus increase access to medical care and long-term surveillance for populations with pre-existing conditions. However, childhood cancer survivors' coverage priorities and familiarity with the ACA are unknown.

Methods

Between May 2011 and April 2012, we surveyed a randomly selected, age-stratified sample of 698 survivors and 210 siblings from the Childhood Cancer Survivor Study.

Results

Overall, 89.8% of survivors and 92.1% of siblings were insured. Many features of insurance coverage that survivors considered “very important” are addressed by the ACA, including increased availability of primary care (94.6%), no waiting period before coverage initiation (79.0%), and affordable premiums (88.1%). Survivors were more likely than siblings to deem primary care physician coverage and choice, protections from costs due to pre-existing conditions, and no start-up period as “very important” (P < .05 for all). Only 27.3% of survivors and 26.2% of siblings reported familiarity with the ACA (12.1% of uninsured v 29.0% of insured survivors; odds ratio, 2.86; 95% CI, 1.28 to 6.36). Only 21.3% of survivors and 18.9% of siblings believed the ACA would make it more likely that they would get quality coverage. Survivors' and siblings' concerns about the ACA included increased costs, decreased access to and quality of care, and negative impact on employers and employees.

Conclusion

Although survivors' coverage preferences match many ACA provisions, survivors, particularly uninsured survivors, were not familiar with the ACA. Education and assistance, perhaps through cancer survivor navigation, are critically needed to ensure that survivors access coverage and benefits.
Risk Factors and Tumor Characteristics of Interval Cancers by Mammographic Density
Authors: Holm Johanna , Humphreys Keith , Li Jingmei , Ploner Alexander , Cheddad Abbas , Eriksson Mikael , Törnberg Sven , Hall Per , Czene Kamila
Published: February 2015

Purpose

To compare tumor characteristics and risk factors of interval breast cancers and screen-detected breast cancers, taking mammographic density into account.

Patients and Methods

Women diagnosed with invasive breast cancer from 2001 to 2008 in Stockholm, Sweden, with data on tumor characteristics (n = 4,091), risk factors, and mammographic density (n = 1,957) were included. Logistic regression was used to compare interval breast cancers with screen-detected breast cancers, overall and by highest and lowest quartiles of percent mammographic density.

Results

Compared with screen-detected breast cancers, interval breast cancers in nondense breasts (≤ 20% mammographic density) were significantly more likely to exhibit lymph node involvement (odds ratio [OR], 3.55; 95% CI, 1.74 to 7.13) and to be estrogen receptor negative (OR, 4.05; 95% CI, 2.24 to 7.25), human epidermal growth factor receptor 2 positive (OR, 5.17; 95% CI, 1.64 to 17.01), progesterone receptor negative (OR, 2.63; 95% CI, 1.58 to 4.38), and triple negative (OR, 5.33; 95% CI, 1.21 to 22.46). In contrast, interval breast cancers in dense breasts (> 40.9% mammographic density) were less aggressive than interval breast cancers in nondense breasts (overall difference, P = .008) and were phenotypically more similar to screen-detected breast cancers. Risk factors differentially associated with interval breast cancer relative to screen-detected breast cancer after adjusting for age and mammographic density were family history of breast cancer (OR, 1.32; 95% CI, 1.02 to 1.70), current use of hormone replacement therapy (HRT; OR, 1.84; 95% CI, 1.38 to 2.44), and body mass index more than 25 kg/m2 (OR, 0.49; 95% CI, 0.29 to 0.82).

Conclusion

Interval breast cancers in women with low mammographic density have the most aggressive phenotype. The effect of HRT on interval breast cancer risk is not fully explained by mammographic density. Family history is associated with interval breast cancers, possibly indicating disparate genetic background of screen-detected breast cancers and interval breast cancers.
Metabolic Changes Induced by the Biliopancreatic Diversion in Diet-Induced Obesity in Male Rats: The Contributions of Sleeve Gastrectomy and Duodenal Switch
Authors: Baraboi Elena-Dana , Li Wei , Labbé Sébastien M. , Roy Marie-Claude , Samson Pierre , Hould Frédéric-Simon , Lebel Stéphane , Marceau Simon , Biertho Laurent , Richard Denis
Published: February 2015

The mechanisms underlying the body weight and fat loss after the biliopancreatic diversion with duodenal switch (BPD/DS) remain to be fully delineated. The aim of this study was to examine the contributions of the two main components of BPD/DS, namely sleeve gastrectomy (SG) and duodenal switch (DS), on energy balance changes in rats rendered obese with a high-fat (HF) diet. Three different bariatric procedures (BPD/DS, SG, and DS) and three sham surgeries were performed in male Wistar rats. Sham-operated animals fed HF were either fed ad libitum (Sham HF) or pair weighed (Sham HF PW) by food restriction to the BPD/DS rats. A group of sham-operated rats was kept on standard chow and served as normal diet control (Sham Chow). All three bariatric surgeries resulted in a transient reduction in food intake. SG per se induced a delay in body weight gain. BPD/DS and DS led to a noticeable gut malabsorption and a reduction in body weight and fat gains along with significant elevations in plasma levels of glucagon-like peptide-17–36 and peptide YY. BPD/DS and DS elevated energy expenditure above that of Sham HF PW during the dark phase. However, they reduced the volume, oxidative metabolism, and expression of thermogenic genes in interscapular brown adipose tissue. Altogether the results of this study suggest that the DS component of the BPD/DS, which led to a reduction in digestible energy intake while sustaining energy expenditure, plays a key role in the improvement in the metabolic profile led by BPD/DS in rats fed a HF diet.
Two-Year Changes in Bone Density After Roux-en-Y Gastric Bypass Surgery
Authors: Yu Elaine W. , Bouxsein Mary L. , Putman Melissa S. , Monis Elizabeth L. , Roy Adam E. , Pratt Janey S. A. , Butsch W. Scott , Finkelstein Joel S.
Published: February 2015

Context:

Bariatric surgery is increasingly popular but may lead to metabolic bone disease.

Objective:

The objective was to determine the rate of bone loss in the 24 months after Roux-en-Y gastric bypass.

Design and Setting:

This was a prospective cohort study conducted at an academic medical center.

Participants:

The participants were adults with severe obesity, including 30 adults undergoing gastric bypass and 20 nonsurgical controls.

Outcomes:

We measured bone mineral density (BMD) at the lumbar spine and proximal femur by quantitative computed tomography (QCT) and dual-energy x-ray absorptiometry at 0, 12, and 24 months. BMD and bone microarchitecture were also assessed by high-resolution peripheral QCT, and estimated bone strength was calculated using microfinite element analysis.

Results:

Weight loss plateaued 6 months after gastric bypass but remained greater than controls at 24 months (−37 ± 3 vs −5 ± 3 kg [ mean ± SEM]; P < .001). At 24 months, BMD was 5–7% lower at the spine and 6–10% lower at the hip in subjects who underwent gastric bypass compared with nonsurgical controls, as assessed by QCT and dual-energy x-ray absorptiometry (P < .001 for all). Despite significant bone loss, average T-scores remained in the normal range 24 months after gastric bypass. Cortical and trabecular BMD and microarchitecture at the distal radius and tibia deteriorated in the gastric bypass group throughout the 24 months, such that estimated bone strength was 9% lower than controls. The decline in BMD persisted beyond the first year, with rates of bone loss exceeding controls throughout the second year at all skeletal sites. Mean serum calcium, 25(OH)-vitamin D, and PTH were maintained within the normal range in both groups.

Conclusions:

Substantial bone loss occurs throughout the 24 months after gastric bypass despite weight stability in the second year. Although the benefits of gastric bypass surgery are well established, the potential for adverse effects on skeletal integrity remains an important concern.
What Changes Are Needed to Enable the Safety Net to Become a Provider of Choice? And How Does It Get Done?
Authors: Kahn Howard A.
Published: February 2015

The safety net is the delivery system that provides health care to low-income and uninsured populations. Following the recent implementation of health care reform, hundreds of thousands of people in Los Angeles County gained or became eligible for health care coverage. The safety net now has the potential to remain a regular source of care for these newly covered patients who historically have been dependent on the safety net for their health care. Safety net providers may need to rethink current practices, operate more efficiently, document more consistently, and improve patient experience to keep and attract this newly insured population. Faced with an uncertain future, safety net clinics and hospitals will need to strategically plan for the coming years, with patient choice at the core of their decisions. Given the newly ensured Medicaid beneficiaries, the safety net will need to evolve and adapt to ensure its role in Los Angeles County.
Safety Net Integration: A Shared Strategy for Becoming Providers of Choice
Authors: Murphy Julia , Ko Michelle , Kizer Kenneth W. , Bindman Andrew B.
Published: February 2015

With the expansion of coverage as a result of federal health care reform, safety net providers are confronting a challenge to care for the underserved while also competing as a provider of choice for the newly insured. Safety net institutions may be able to achieve these goals by pursuing greater delivery system integration. We interviewed safety net hospital and community health center (CHCs) leaders in five US cities to determine what strategies these organizations are employing to promote care integration in the safety net. Although there is some experimentation with payment reform and health information exchange, safety net providers identify significant policy and structural barriers to integrating service delivery. The enhanced Medicaid payments for CHCs and the federal requirement that CHCs retain independent boards discourage these organizations from integrating with other safety net providers. Current policies are not mobilizing safety net providers to pursue integration as a way to deliver more efficient and effective care. Medicaid and other policies at the federal and state level could be revised to overcome known fragmentation in the health care safety net. This includes addressing the conflicts in financing and governance arrangements that are encouraging providers to resist integration to preserve their independence.
The Price of Experience
Authors: Jeong Hyeok , Kim Yong , Manovskii Iourii
Published: February 2015

We identify a key role of factor supply, driven by demographic changes, in shaping several empirical regularities that are a focus of active research in macro and labor economics. In particular, demographic changes alone can account for the large movements of the return to experience over the last four decades, for the differential dynamics of the age premium across education groups emphasized by Katz and Murphy (1992), for the differential dynamics of the college premium across age groups emphasized by Card and Lemieux (2001), and for the changes in cross-sectional and cohort-based life-cycle profiles emphasized by Kambourov and Manovskii (2005). (JEL D91, E24, I23, J11, J24, J31)
Information Disclosure as a Matching Mechanism: Theory and Evidence from a Field Experiment
Authors: Tadelis Steven , Zettelmeyer Florian
Published: February 2015

Market outcomes depend on the quality of information available to its participants. We measure the effect of information disclosure on market outcomes using a large-scale field experiment that randomly discloses quality information in wholesale automobile auctions. We argue that buyers in this market are horizontally differentiated across cars that are vertically ranked by quality. This implies that information disclosure helps match heterogeneous buyers to cars of varying quality, causing both good and bad news to increase competition and revenues. The data confirm these hypotheses. These findings have implications for the design of other markets, including e-commerce, procurement auctions, and labor markets. (JEL C93, D44, D82, L15)
The Impact of the Great Migration on Mortality of African Americans: Evidence from the Deep South
Authors: Black Dan A. , Sanders Seth G. , Taylor Evan J. , Taylor Lowell J.
Published: February 2015

The Great Migration—the massive migration of African Americans out of the rural South to largely urban locations in the North, Midwest, and West—was a landmark event in US history. Our paper shows that this migration increased mortality of African Americans born in the early twentieth century South. This inference comes from an analysis that uses proximity of birthplace to railroad lines as an instrument for migration. (JEL I12, J15, N31, N32, N91, N92, R23)