bluuebunny/crossref_metadata_2025 huggingface dataset:
Rectus Femoris Transfer Versus Rectus Intramuscular Lengthening for the Treatment of Stiff Knee Gait in Children With Cerebral Palsy
Authors: Ellington Matthew D. , Scott Allison C. , Linton Judith , Sullivan Elroy , Barnes Douglas
Published: January 2018

Background:

Rectus femoris transfer (RFT) is used to treat stiff knee gait in spastic cerebral palsy. Recently, rectus femoris lengthening has been reported as treatment for stiff knee gait. The purpose of this study was to compare short-term outcomes of 2 surgical procedures.

Methods:

A retrospective chart review of 23 patients (42 limbs) with diplegic spastic cerebral palsy who had undergone rectus femoris intramuscular lengthening for treatment of stiff knee gait with a Gross Motor Function Classification System level I, II, or III was completed. These patients were matched with a cohort of 23 patients (42 limbs) who had undergone RFTs based on age, sex, Gross Motor Function Classification System level, diagnosis, preoperative Gait Deviation Index, and any simultaneous surgeries. Preoperative and 1 year postoperative motion analysis data and physical examination were compared.

Results:

There were no significant differences in demographics between the groups. On physical examination, a positive postoperative Duncan-Ely test was seen significantly less often in the transfer limbs (20 vs. 37). Average postoperative quad tone score was 1.56 for the transfer group compared with 2.19 for the lengthening group. No significant postoperative difference was seen between groups in stride length, walking speed, cadence, knee flexion at initial contact, peak knee flexion during loading response, mean knee flexion in stance, peak knee flexion in swing, time to peak knee flexion (% swing), time to peak knee flexion (% gait cycle), Gait Deviation Index or total knee range of motion. There was a difference in time to achieve 90 degrees passive knee flexion with the lengthening group reaching this in 8.3 days and transfer group in 15.3 days (P<0.0001).

Conclusions:

Motion analysis parameters showed results of RFT and rectus femoris intramuscular lengthening to be equivalent 1 year postoperatively. Since rectus femoris lengthening is technically less difficult and rehabilitation faster, rectus femoris lengthening may be preferred if long-term follow-up supports these findings.

Level of Evidence:

Level III—retrospective comparative study.
Targeting Transfusion-Related Acute Lung Injury: The Journey From Basic Science to Novel Therapies
Authors: Semple John W. , McVey Mark J. , Kim Michael , Rebetz Johan , Kuebler Wolfgang M. , Kapur Rick
Published: January 2018

Objectives:

Transfusion-related acute lung injury is characterized by the onset of respiratory distress and acute lung injury following blood transfusion, but its pathogenesis remains poorly understood. Generally, a two-hit model is presumed to underlie transfusion-related acute lung injury with the first hit being risk factors present in the transfused patient (such as inflammation), whereas the second hit is conveyed by factors in the transfused donor blood (such as antileukocyte antibodies). At least 80% of transfusion-related acute lung injury cases are related to the presence of donor antibodies such as antihuman leukocyte or antihuman neutrophil antibodies. The remaining cases may be related to nonantibody-mediated factors such as biolipids or components related to storage and ageing of the transfused blood cells. At present, transfusion-related acute lung injury is the leading cause of transfusion-related fatalities and no specific therapy is clinically available. In this article, we critically appraise and discuss recent preclinical (bench) insights related to transfusion-related acute lung injury pathogenesis and their therapeutic potential for future use at the patients’ bedside in order to combat this devastating and possibly fatal complication of transfusion.

Data Sources:

We searched the PubMed database (until August 22, 2017).

Study Selection:

Using terms: “Transfusion-related acute lung injury,” “TRALI,” “TRALI and therapy,” “TRALI pathogenesis.”

Data Extraction:

English-written articles focusing on transfusion-related acute lung injury pathogenesis, with potential therapeutic implications, were extracted.

Data Synthesis:

We have identified potential therapeutic approaches based on the literature.

Conclusions:

We propose that the most promising therapeutic strategies to explore are interleukin-10 therapy, down-modulating C-reactive protein levels, targeting reactive oxygen species, or blocking the interleukin-8 receptors; all focused on the transfused recipient. In the long-run, it may perhaps also be advantageous to explore other strategies aimed at the transfused recipient or aimed toward the blood product, but these will require more validation and confirmation first.
Effect of Emergency Department and ICU Occupancy on Admission Decisions and Outcomes for Critically Ill Patients*
Authors: Mathews Kusum S. , Durst Matthew S. , Vargas-Torres Carmen , Olson Ashley D. , Mazumdar Madhu , Richardson Lynne D.
Published: January 2018

Objectives:

ICU admission delays can negatively affect patient outcomes, but emergency department volume and boarding times may also affect these decisions and associated patient outcomes. We sought to investigate the effect of emergency department and ICU capacity strain on ICU admission decisions and to examine the effect of emergency department boarding time of critically ill patients on in-hospital mortality.

Design:

A retrospective cohort study.

Setting:

Single academic tertiary care hospital.

Patients:

Adult critically ill emergency department patients for whom a consult for medical ICU admission was requested, over a 21-month period.

Interventions:

None.

Measurements and Main Results:

Patient data, including severity of illness (Mortality Probability Model III on Admission), outcomes of mortality and persistent organ dysfunction, and hourly census reports for the emergency department, for all ICUs and all adult wards were compiled. A total of 854 emergency department requests for ICU admission were logged, with 455 (53.3%) as “accept” and 399 (46.7%) as “deny” cases, with median emergency department boarding times 4.2 hours (interquartile range, 2.8–6.3 hr) and 11.7 hours (3.2–20.3 hr) and similar rates of persistent organ dysfunction and/or death 41.5% and 44.6%, respectively. Those accepted were younger (mean ±sd, 61 ± 17 vs 65 ± 18 yr) and more severely ill (median Mortality Probability Model III on Admission score, 15.3% [7.0–29.5%] vs 13.4% [6.3–25.2%]) than those denied admission. In the multivariable model, a full medical ICU was the only hospital-level factor significantly associated with a lower probability of ICU acceptance (odds ratio, 0.55 [95% CI, 0.37–0.81]). Using propensity score analysis to account for imbalances in baseline characteristics between those accepted or denied for ICU admission, longer emergency department boarding time after consult was associated with higher odds of mortality and persistent organ dysfunction (odds ratio, 1.77 [1.07–2.95]/log10hour increase).

Conclusions:

ICU admission decisions for critically ill emergency department patients are affected by medical ICU bed availability, though higher emergency department volume and other ICU occupancy did not play a role. Prolonged emergency department boarding times were associated with worse patient outcomes, suggesting a need for improved throughput and targeted care for patients awaiting ICU admission.
Evidence- and Consensus-Based Guidelines for the Management of Communication and Swallowing Disorders Following Pediatric Traumatic Brain Injury
Authors: Mei Cristina , Anderson Vicki , Waugh Mary-Clare , Cahill Louise , Morgan Angela T.
Published: January 2018

Objective:

Evidence-based management guidelines for communication and swallowing disorders following pediatric traumatic brain injury (TBI) are scarcely available, potentially resulting in suboptimal outcomes. To improve clinical care of this population, a multidisciplinary guideline development committee was formed to develop evidence-based recommendation (EBR) and consensus-based recommendation (CBR) for the management of speech, language, and swallowing disorders during the first year of recovery.

Methods:

A 3-round Delphi survey was completed by the committee to reach agreement (80% consensus) for the CBRs. Systematic review evidence guided development of EBRs, devised using the National Health and Medical Research Council statement form.

Results:

Altogether, 30 recommendations (5 EBRs and 25 CBRs) were developed to guide management of speech, language, and swallowing disorders, including prediction of these disorders; health team required, optimal timing of assessment; assessment tools; intervention strategies and commencement of treatment; and key information to support parents.

Conclusion:

The developed recommendations provide a basis for the systematic management of communication and swallowing disorders to be refined as new evidence emerges. Key recommendations include screening of children with moderate/severe TBI for these disorders acutely using specified measures. Patients with severe TBI and prolonged ventilation are a particular at-risk group and should be considered for early referral to speech–language pathology to support timely diagnosis and management. No evidence was identified to support an EBR for treatment, highlighting a key area for research.
Regenerative Therapy for Fuchs Endothelial Corneal Dystrophy
Authors: Soh Yu Qiang , Mehta Jodhbir S.
Published: January 2018

Purpose:

Fuchs endothelial corneal dystrophy (FECD) is an acquired corneal endotheliopathy and is one of the most common indications for corneal transplantation surgery worldwide. Endothelial keratoplasty (EK) is the most popular form of corneal transplantation for FECD. In standard EK surgery, the patient's corneal endothelium and basement membrane [ie, Descemet membrane (DM)] are first removed, followed by transplantation of donor tissue that comprises allogenic corneal endothelial cells, DM, and corneal stroma of variable thickness. We hypothesized that in lieu of EK, transplantation of acellular DM (ie, Descemet membrane transplantation, DMT) may similarly restore anatomical and functional integrity of the corneal endothelium, by stimulating centripetal migration of peripheral host corneal endothelial cells.

Methods:

A case report of a first-in-human trial of DMT for treatment of FECD is presented.

Results:

A patient with FECD was successfully treated with DMT. Her preoperative best-corrected Snellen visual acuity (BCVA) was 6/18, central corneal thickness was 603 nm, and central corneal endothelial cell density was unrecordable. By postoperative month 6, her best-corrected Snellen visual acuity had improved to 6/7.5, central corneal thickness was 569 nm, and central corneal endothelial cell density was 889 cells/mm2. She remained stable despite complete cessation of all medications including immunosuppressants. No significant postoperative complications have been encountered.

Conclusions:

DMT may be effective for treatment of FECD. Achievement of endothelial regeneration without allogenic corneal endothelial cell transplantation and exposure to the attendant risks of graft rejection and chronic immunosuppression represents a significant improvement from the current paradigm of EK.
Ophthalmologic Approach in Epidermolysis Bullosa: A Cross-Sectional Study With Phenotype–Genotype Correlations
Authors: Mellado Felipe , Fuentes Ignacia , Palisson Francis , I. Vergara José , Kantor Arturo
Published: January 2018

Purpose:

This study describes ophthalmologic and systemic clinical findings in different subtypes of epidermolysis bullosa (EB) establishing genotype–phenotype correlations.

Methods:

A cross-sectional study was conducted in 58 patients with EB together with the Dystrophic Epidermolysis Bullosa Research Association, Chile. Data were stratified by major subtypes such as “simplex epidermolysis bullosa” (EBS), “junctional epidermolysis bullosa” (JEB), “recessive and dominant dystrophic epidermolysis bullosa” and “dominant dystrophic epidermolysis bullosa” (DDEB), and “Kindler syndrome” (KS). The diagnosis was confirmed by skin immunofluorescence mapping and genetic testing. Best-corrected visual acuity, corneal erosions, corneal scarring, symblepharon, blepharitis, ectropion, limbal stem cell deficiency, and esophageal involvement were assessed. Clinical outcome was based on the presence of corneal involvement attributable to EB.

Results:

The most common ocular manifestations were corneal erosion/scarring and recurrent erosions. Frequencies of the EB subtypes were as follows: 17% EBS, 12% JEB, 16% DDEB, 53% recessive and DDEB, and 2% KS. Patients with EBS and DDEB did not reveal ocular involvement. Patients with recessive dystrophic epidermolysis bullosa (RDEB) were most affected by the disease showing corneal involvement in 16 cases, whereas 2 patients with JEB and the single KS case also showed corneal disease. Before their visit, 24 patients had undergone esophageal dilation, 23 of them with RDEB and 1 with KS.

Conclusions:

Although ophthalmic complications are common in EB, the incidence varied with the EB subtype. We also establish the correlation between esophageal and corneal involvement in RDEB.
Descemet Stripping Automated Endothelial Keratoplasty for Failed Penetrating Keratoplasty: Influence of the Graft–Host Junction on the Graft Survival Rate
Authors: Omoto Takashi , Sakisaka Toshihiro , Toyono Tetsuya , Yoshida Junko , Shirakawa Rika , Miyai Takashi , Yamagami Satoru , Usui Tomohiko
Published: January 2018

Purpose:

To investigate the clinical results of Descemet stripping automated endothelial keratoplasty (DSAEK) for failed penetrating keratoplasty (PK) and the influence of the graft–host junction (GHJ) on the graft survival rate.

Methods:

Data were retrospectively collected on patient demographics, visual outcomes, complications, and graft survival rate for 17 eyes of 16 patients who underwent DSAEK for failed PK. The graft survival rate was compared between the eyes when divided into a bump group and a well-aligned group according to the shape of the GHJ detected on anterior segment optical coherence tomography.

Results:

The most common indication for initial PK was bullous keratopathy after glaucoma surgery (35.3%). Seven eyes (41.2%) were classified into the bump group and 10 eyes (58.8%) into the well-aligned group. The mean best-ever documented visual acuity (BDVA) after DSAEK was 0.33 logMAR. Postoperatively, almost 70% of eyes achieved a BDVA that was within 0.2 logMAR of their preoperative BDVA. Graft detachment occurred in 29.4% of eyes and primary graft failure in 17.6%. All primary failures occurred in the bump group. The cumulative graft survival rate was 82.3% at 1 year, 73.2% at 2 years, and 58.6% at 3 years. Graft failure was more likely in eyes in the bump group than in those in the well-aligned group (P = 0.037, Wilcoxon test).

Conclusions:

DSAEK for failed PK had a favorable outcome in this study. However, the GHJ should be assessed carefully before performing the procedure.
Nonalcoholic fatty liver disease: biomarkers as diagnostic tools for liver damage assessment in adult patients from Argentina
Authors: Valva Pamela , Rios Daniela , Casciato Paola , Gadano Adrián , Galdame Omar , Mullen Eduardo , Bertot Gustavo , de Matteo Elena , Preciado María V.
Published: January 2018

Background

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease whose prevalence has been increasing constantly and linked to the global obesity epidemic. The NAFLD histologic spectrum ranges from simple steatosis to nonalcoholic steatohepatitis (NASH), which can progress to cirrhosis and hepatocellular carcinoma. Liver biopsy is the only reliable means to diagnose and stage NASH, but its invasive nature limits its use. Therefore, the prediction of hepatic injury by means of the development of new noninvasive tests represents a growing medical need. Our aim was to evaluate matrix deposition and cell-death markers, which correlate with liver injury in an NAFLD patient cohort.

Patients and methods

Liver biopsies and serum from 34 NAFLD adult patients were analyzed. Histological parameters were evaluated. Matrix deposition [hyaluronic acid (HA) and tissue inhibitor of matrix metalloproteinase inhibitor-1 (TIMP-1)] and cell-death markers [cytokeratin-18 (M65) and caspase-cleaved cytokeratin-18 (M30)] were measured in serum samples.

Results

HA showed an association with fibrosis severity (P=0.03) and M30 with steatosis (P=0.013), inflammation (P=0.004), and fibrosis severity (P=0.04). In contrast, TIMP-1 and M65 showed no association with any histological parameter of liver injury. The evaluation of diagnostic accuracy showed good performance as less invasive markers of significant fibrosis of both HA (area under the receiver operating characteristic curve: 0.928) and M30 (area under the receiver operating characteristic curve: 0.848).

Conclusion

Biomarkers are essential tools that may provide a quick and accurate diagnosis for patients with life-threatening NAFLD and NASH. HA and M30, together or determined sequentially, have been found to be straightforward tests that may be sufficient to predict significant fibrosis even in a primary care center of an underdeveloped country.
‘Knocking-fingers’ chest compression technique in infant cardiac arrest: single-rescuer manikin study
Authors: Jung Woo Jin , Hwang Sung Oh , Kim Hyung Il , Cha Yong Sung , Kim Oh Hyun , Kim Hyun , Lee Kang Hyun , Cha Kyoung-Chul
Published: January 2018

Objective

We designed a new chest compression technique, the ‘knocking-fingers’ chest compression (KF) technique, for a single rescuer in infant cardiac arrest. We compared the effectiveness and feasibility between the KF technique and the two-finger (TF) and two-thumb encircling hands (TT) techniques.

Participants and methods

A prospective, randomized, crossover study was carried out to compare the quality of chest compression and ventilation between the KF, TF, and TT techniques using a 30: 2 compression-to-ventilation ratio and mouth-to-mouth ventilation. The area of chest compression, finger(s) pain, and fatigability were measured to compare safety and feasibility.

Results

The total frequency of chest compression for 5 min was the highest with the KF technique, followed by the TF and TT techniques. The total frequency of ventilation for 5 min was higher with the KF and TF techniques compared with the TT technique. The total hands-off time was the shortest with the KF technique, followed by the TF and TT techniques. The area of chest compression was the smallest in KF technique. Participants complained of severe finger pain and high fatigability in TF technique.

Conclusion

The single-rescuer KF chest compression technique is an effective alternative to the TF or TT techniques for infant cardiac arrest.
A Transactional “Second-Victim” Model—Experiences of Affected Healthcare Professionals in Acute-Somatic Inpatient Settings: A Qualitative Metasynthesis
Authors: Schiess Cornel , Schwappach David , Schwendimann René , Vanhaecht Kris , Burgstaller Melanie , Senn Beate
Published: January 2018

Background

“Second victims” are healthcare professionals traumatized by involvement in significant adverse events. Associated burdens, e.g., guilt, can impair professional performance, thereby endangering patient safety. To date, however, a model of second victims’ experiences toward a deeper understanding of qualitative studies is missing. Therefore, we aimed to identify, describe, and interpret these experiences in acute-somatic inpatient settings.

Methods

This qualitative metasynthesis reflects a systematic literature search of PubMed, CINAHL, and PsycINFO, extended by hand searches and expert consultations. Two researchers independently evaluated qualitative studies in German and English, assessing study quality via internationally approved criteria. Results were analyzed inductively and aggregated quantitatively.

Results

Based on 19 qualitative studies (explorative-descriptive: n = 13; grounded theory: n = 3; phenomenology: n = 3), a model of second-victim experience was drafted. This depicts a multistage developmental process: in appraising their situation, second victims focus on their involvement in an adverse event, and they become traumatized. To restore their integrity, they attempt to understand the event and to act accordingly; however, their reactions are commonly emotional and issue focused. Outcomes include leaving the profession, surviving, or thriving. This development process is alternately modulated by safety culture and healthcare professionals.

Conclusions

For the first time, this model works systematically from the second-victim perspective based on qualitative studies. Based on our findings, we recommend integrating second victims’ experiences into safety culture and root-cause analyses. Our transactional model of second-victim experience provides a foundation for strategies to maintain and improve patient safety.
Volume at First Leak Is Associated With Sling Failure Among Women With Stress Urinary Incontinence
Authors: Hill Bryan , Fletcher Sarah , Blume Jeffrey , Adam Rony , Ward Renée
Published: January 2018

Introduction

Stress urinary incontinence at a low bladder volume is a clinically observed phenomenon that is not well studied with regard to treatment outcomes. The primary aim of our study was to determine if the volume at first leak is associated with sling outcome.

Methods

This is a retrospective cohort study evaluating whether urodynamic stress urinary incontinence observed at low volumes is associated with sling failure using the Synthetic Derivative database. Sling failure was defined as (1) undergoing a subsequent surgery for stress incontinence (eg, urethral bulking agent, repeat sling) or (2) leakage that was subjectively worse or unchanged from baseline. Sling success was defined as subjective improvement in incontinence or being dry. Intrinsic sphincter deficiency was defined as maximum urethral closure pressure 20 cm H20 or less or abdominal leak point pressure less than 60 cm H20.

Results

Outcome data were available for 168 of 206 women who underwent a sling after urodynamic testing from 2006 to 2014. Of the 168 women, 80 were transobturator, 79 were retropubic, 8 lacked data regarding the approach to the midurethral sling, and 1 was an autologous pubovaginal sling. Similar failure rates were seen for transobturator (10%) and retropubic slings (7.6%). Preoperative urodynamic parameters, such as cystometric capacity and intrinsic sphincter deficiency, were similar among failed and successful slings. For every additional 50 mL in bladder volume at first leak (SUIvol), there was a 1.6 increased odds of having a successful sling (odds ratio, 1.576; 95% confidence interval, 1.014–2.450; P = 0.04). There was no statistically significant association between maximum urethral closure pressure, abdominal leak point pressure, body mass index, age, sling type, or whether a prior anti-incontinence procedure had been performed and sling success.

Conclusions

Bladder volume at first leak is a strong predictor of sling failure.
Impact of a statewide trauma system on the triage, transfer, and inpatient mortality of injured patients
Authors: Porter Austin , Karim Saleema , Bowman Stephen M. , Recicar John , Bledsoe Gregory H. , Maxson Robert T.
Published: January 2018

BACKGROUND

In 2009, Arkansas implemented a statewide trauma system to address the high rates of mortality and morbidity due to trauma. The principal objective of the Arkansas Trauma System is to transport patients to the appropriate facility based on the injuries of the patients. This study evaluated four metrics that were crucial to system health. These measures included: treatment location, scene triage, admission to nondesignated facilities, and inpatient mortality. Furthermore, the authors sought to quantify how the system is selective toward the severely injured regarding triage and treatment location. The authors hypothesized that system implementation should increase the proportion of patients, particularly the severely injured, treated at Level I/II facilities. The system should increase the proportion of patients, especially the severely injured, admitted to Level I/II facilities directly from the scene. The system should result in fewer patients admitted to nondesignated facilities. Lastly, system implementation should result in fewer inpatient deaths.

METHODS

A pre-post study design was used for this evaluation. Data from the Arkansas Hospital Discharge data set (2007 through 2012) identified patients who were admitted as a result of their injuries. The ICD-MAP software was used to categorize those with and without severe injuries based on an Injury Severity Score of 16 or greater or head Abbreviated Injury Scale score of 3 or greater.

RESULTS

The results indicate that while there was an overall increase in odds of patients being admitted to Level I/II facilities, those with severe injuries were associated with an even greater odds of admission to Level I/II facilities (p < 0.0001). System implementation was also associated with more severely injured patients admitted to Level I/II facilities from the scene. There were also fewer patients admitted to nondesignated hospitals after system implementation (p < 0.0001). System implementation was associated with fewer inpatient deaths (p = 0.02).

CONCLUSION

Two years after implementation, the trauma system showed significant progress. The measures evaluated in this study are believed to support the effectiveness of the trauma system.

LEVEL OF EVIDENCE

Therapeutic study, level IV.
A Case of Drug-Induced Severe Endocrinopathies
Authors: Villarreal Joshua , Townes David , Vrablik Michael , Ro Kumhee
Published: January 2018

The purpose of this article is to present a discussion of immune checkpoint inhibitors (ICIs) that are relatively new, yet growing, form of cancer therapy. Immune checkpoint inhibitors increase host immune response against neoplastic cells. Strengthened immunological response increases the potential for adverse events such as life-threatening endocrinopathies. The case of a 66-year-old man with metastatic melanoma treated with nivolumab and ipilimumab presented to the emergency department with marked hyperglycemia and elevated anion gap 19 days after receiving both agents is discussed. The patient received a diagnosis of immune-mediated diabetes requiring ongoing insulin even after discontinuation of ICIs. As treatment with this class of agents expands, emergency department providers will need to become familiar with the identification of their adverse reactions to provide the proper management of care.
Neurostimulation for drug-resistant epilepsy: a systematic review of clinical evidence for efficacy, safety, contraindications and predictors for response
Authors: Boon Paul , De Cock Elien , Mertens Ann , Trinka Eugen
Published: January 2018

Purpose of review

Neurostimulation is becoming an increasingly accepted treatment alternative for patients with drug-resistant epilepsy (DRE) who are unsuitable surgery candidates. Standardized guidelines on when or how to use the various neurostimulation modalities are lacking. We conducted a systematic review on the currently available neurostimulation modalities primarily with regard to effectiveness and safety.

Recent findings

For vagus nerve stimulation (VNS), there is moderate-quality evidence for its effectiveness in adults with drug-resistant partial epilepsies. Moderate-to-low-quality evidence supports the efficacy and safety of deep brain stimulation (DBS) and responsive neurostimulation (RNS) in patients with DRE. There is moderate-to-very low-quality evidence that transcranial direct current stimulation (tDCS) is effective or well tolerated. For transcutaneous vagus nerve stimulation (tVNS), transcranial magnetic stimulation (TMS) and trigeminal nerve stimulation (TNS), there are insufficient data to support the efficacy of any of these modalities for DRE. These treatment modalities, nevertheless, appear well tolerated, with no severe adverse events reported.

Head-to-head comparison of treatment modalities such as VNS, DBS and RNS across different epileptic syndromes are required to decide which treatment modality is the most effective for a given patient scenario. Such studies are challenging and it is unlikely that data will be available in the near future. Additional data collection on potentially promising noninvasive neurostimulation modalities like tVNS, TMS, TNS and tDCS is warranted to get a more precise estimate of their therapeutic benefit and long-term safety.
LFMM 2.0: Latent factor models for confounder adjustment in genome and epigenome-wide association studies
Authors: Caye Kevin , Jumentier Basile , François Olivier
Published: January 2018

Motivation

Genome-wide, epigenome-wide and gene-environment association studies are plagued with the problems of confounding and causality. Although those problems have received considerable attention in each application field, no consensus have emerged on which approaches are the most appropriate to solve this problem. Current methods use approximate heuristics for estimating confounders, and often ignore correlation between confounders and primary variables, resulting in suboptimal power and precision.

Results

In this study, we developed a least-squares estimation theory of confounder estimation using latent factor models, providing a unique framework for several categories of genomic data. Based on statistical learning methods, the proposed algorithms are fast and efficient, and can be proven to provide optimal solutions mathematically. In simulations, the algorithms outperformed commonly used methods based on principal components and surrogate variable analysis. In analysis of methylation profiles and genotypic data, they provided new insights on the molecular basis of diseases and adaptation of humans to their environment.

Availability and implementation

Software is available in the R package lfmm athttps://bcm-uga.github.io/lfmm/.
Analog Signalling with ‘Digital’ Molecular Switches
Authors: Clarke Stephen E
Published: January 2018

Molecular switches, such as the protein kinase CaMKII, play a fundamental role in cell signalling by decoding inputs into either high or low states of activity; because the high activation state can be turned on and persist after the input ceases, these switches have earned a reputation as ‘digital’. Although this on/off, binary perspective has been valuable for understanding long timescale synaptic plasticity, accumulating experimental evidence suggests that the CaMKII switch can also control plasticity on short timescales. To investigate this idea further, a non-autonomous, nonlinear ordinary differential equation, representative of a general bistable molecular switch, is analyzed. The results suggest that switch activity in regions surrounding either the high- or low-stable states of activation could act as a reliable analog signal, whose short timescale fluctuations relative to equilibrium track instantaneous input frequency. The model makes intriguing predictions and is validated against previous work demonstrating its suitability as a minimal representation of switch dynamics; in combination with existing experimental evidence, the theory suggests a multiplexed encoding of instantaneous frequency information over short timescales, with integration of total activity over long timescales.

Author Summary

Bistable molecular switches can decode cellular inputs into distinct high- or low-states of persistent enzymatic activity. Although this on-off, ‘digital’ perspective is valuable for long timescales, I suggest that short timescale fluctuations of switch activity around either stable state acts as an analog signal that reliably encodes instantaneous input frequency. A minimal model and theory make predictions about the molecular switch CaMKII, synaptic plasticity and burst detection.
Label-free assessment of red blood cell storage lesions by deep learning
Authors: Doan M. , Sebastian J. A. , Pinto R. N. , McQuin C. , Goodman A. , Wolkenhauer O. , Parsons M. J. , Acker J. P. , Rees P. , Hennig H. , Kolios M. C. , Carpenter A. E.
Published: January 2018

Blood transfusion is a life-saving clinical procedure. With millions of units needed globally each year, it is a growing concern to improve product quality and recipient outcomes.

Stored red blood cells (RBCs) undergo continuous degradation, leading to structural and biochemical changes. To analyze RBC storage lesions, complex biochemical and biophysical assays are often employed.

We demonstrate that label-free imaging flow cytometry and deep learning can characterize RBC morphologies during 42-day storage, replacing the current practice of manually quantifying a blood smear from stored blood units. Based only on bright field and dark field images, our model achieved 90% accuracy in classifying six different RBC morphologies associated with storage lesions versus human-curated manual examination. A model fitted to the deep learning-extracted features revealed a pattern of morphological changes within the aging blood unit that allowed predicting the expiration date of stored blood using solely morphological assessment.

Deep learning and label-free imaging flow cytometry could therefore be applied to reduce complex laboratory procedures and facilitate robust and objective characterization of blood samples.
DNA methylation mediates genetic liability to non-syndromic cleft lip/palate
Authors: Howe Laurence J , Richardson Tom G , Arathimos Ryan , Alvizi Lucas , Passos-Bueno Maria-Rita , Stanier Philip , Nohr Ellen , Ludwig Kerstin U , Mangold Elisabeth , Knapp Michael , Stergiakouli Evie , St Pourcain Beate , Davey Smith George , Sandy Jonathan , Relton Caroline L , Lewis Sarah J , Hemani Gibran , Sharp Gemma C
Published: January 2018

Background

Non-syndromic cleft lip/palate (nsCL/P) is a complex trait with genetic and environmental risk factors. Around 40 distinct genetic risk loci have been identified for nsCL/P, but many reside in non-protein-coding regions with an unclear function. We hypothesised that one possibility is that the genetic risk variants influence susceptibility to nsCL/P through gene regulation pathways, such as those involving DNA methylation.

Methods

Using nsCL/P Genome-wide association study summary data and methylation data from four studies, we used Mendelian randomization and joint likelihood mapping to identify putative loci where genetic liability to nsCL/P may be mediated by variation in DNA methylation in blood.

Results

There was evidence at three independent loci, VAX1 (10q25.3), LOC146880 (17q23.3) and NTN1 (17p13.1), that liability to nsCL/P and variation in DNA methylation might be driven by the same genetic variant. Follow up analyses using DNA methylation data, derived from lip and palate tissue, and gene expression catalogues provided further insight into possible biological mechanisms.

Conclusions

Genetic variation may increase liability to nsCL/P by influencing DNA methylation and gene expression at VAX1, LOC146880 and NTN1.
Unsupervised embedding of single-cell Hi-C data
Authors: Liu Jie , Yardımcı Galip Gürkan , Lin Dejun , Noble William Stafford
Published: January 2018

Single-cell Hi-C (scHi-C) data promises to enable scientists to interrogate the 3D architecture of DNA in the nucleus of the cell, studying how this structure varies stochastically or along developmental or cell cycle axes. However, Hi-C data analysis requires methods that take into account the unique characteristics of this type of data. In this work, we explore whether methods that have been developed previously for the analysis of bulk Hi-C data can be applied to scHi-C data. In this work, we apply methods designed for analysis of bulk Hi-C data to scHi-C data in conjunction with unsupervised embedding. We find that one of these methods, HiCRep, when used in conjunction with multidimensional scaling (MDS), strongly outperforms three other methods, including a technique that has been used previously for scHi-C analysis. We also provide evidence that the HiCRep/MDS method is robust to extremely low per-cell sequencing depth, that this robustness is improved even further when high-coverage and low-coverage cells are projected together, and that the method can be used to jointly embed cells from multiple published datasets.
Brownies & Downies: coffee, culture and community: a social innovation that supports the intellectually disabled
Authors: Marks Jonathan , Hidden Karen
Published: January 2018

Subject area

Entrepreneurship; Social entrepreneurship.

Study level/applicability

Graduate level.

Case overview

This paper, The Brownies & Downies case study, aims to examine a social enterprise that provides employment, training and job placements for people with intellectual disability within a trendy artisanal coffee shop in Cape Town, South Africa. The business is based on a similar establishment (same name) in The Netherlands and was brought to Cape Town by Wendy Vermeulen, a Dutch national who completed a social development internship in Cape Town. The case is located within the field of social enterprise with a particular focus on the tension between purpose and profit and the pressure and challenges of replication, growth and scale/expansion. The protagonist in the case is Wade Schultz, Wendy’s business partner, who is grappling with how to not only remain true to the social purpose of the business but also turn a profit in the pressured and competitive coffee industry. He is further challenged by deciding whether to expand the existing training business into other sectors or seek a replication model in other South African cities as a means of growing revenue and increasing the social impact.

Expected learning outcomes

The key learning from this case study are as follows: First, intellectual disability is a hidden form of disability, often misunderstood and subject to prejudice and discriminatory hiring practices. Intellectual disability exists on a scale – some individuals are able to work outside of pretexted or sheltered workspaces. Greater effort is required within open workplaces to sensitive staff to working with/alongside intellectually disabled people. This case illustrates a social enterprise model that seeks to bridge the gap between sheltered workspaces and open workspaces. Second, most social enterprises grapple with the tension between profit and purpose; this case presents a company that is living this dilemma. The importance of remaining true to purpose needs to be balanced carefully against becoming economically self-sufficient; however, the pursuit of profits should not happen at the cost of social mission. Alternate business models are a mechanism to building revenue to support the social objective.

Supplementary materials

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Subject code

CSS: 3: Entrepreneurship.
The impact of marketing activities on service brand equity
Authors: Kumar Ravi Shekhar , Dash Satyabhusan , Malhotra Naresh K.
Published: January 2018

Purpose

This study aims to propose and empirically test new improved customer-based brand equity (CBBE) creation framework, which advocates marketing activities create CBBE through customer experience (CE). The proposed framework is in contrast to extant literature suggesting marketing activities directly create CBBE.

Design/methodology/approach

Qualitative interviews with patients, followed by interaction with respondents using a structured questionnaire, were used to collect the data.

Findings

The results suggest that CE is the focal mediating variable for the relationship between marketing activities and CBBE. Out of 15 marketing activities, 8 positively impacted CBBE through CE and 2 negatively affected CBBE through CE. Among the remaining five, three had only a direct positive impact on CBBE and two neither directly nor indirectly impacted CBBE.

Research limitations/implications

The effects of only individual marketing activity, and not of the interaction among marketing activities, were assessed.

Practical implications

The study provides insights into the importance of CE in building CBBE for credence-dominant services (e.g. healthcare). This work will help managers in implementing experiential marketing by designing suitable activities for creating service CBBE.

Originality/value

The study outlines service CBBE creation through CE, offering specific insights for the healthcare market.
Bringing sensory anthropology to consumer research
Authors: Scott Rebecca O. , Uncles Mark D.
Published: January 2018

Purpose

Multisensory stimulation is integral to experiential consumption. However, a gap persists between recognition of the importance of multisensory stimulation and the research techniques used to study the effects of such stimulation on consumption experiences. This article draws on sensory anthropology to narrow the gap.

Design/methodology/approach

Sensory anthropology has the potential to help consumer researchers understand multisensory stimulation and its effect on consumption experiences. To highlight this potential, ethnographic fieldwork is reported for two related experiential settings: yacht racing and adventure racing.

Findings

It is shown how consumer researchers can apply concepts and data collection techniques from sensory anthropology to derive powerful insights into consumption experiences. A set of guidelines and examples is derived from the embodied concepts associated with sensory anthropology, namely, kinaesthetic schema, bodily mimesis, the mindful body and local biology. These concepts are used to comprehend how consumers experience sensations phenomenologically, understand them culturally and re-enact them socially.

Practical implications

By acknowledging and engaging the senses, researchers can acquire embodied information that would not be evident from the conventional interview, survey or experimental data. Sensory anthropology adds to what is known from psychological, social and cultural sources to enable organisations to differentiate their offerings by means of the senses and sensory expressions, not only in yacht and adventure racing but potentially in many other experiential settings, such as travel, shopping, entertainment and immersive gaming.

Originality/value

This article offers distinct and original methodological insights for consumer researchers by focusing on concepts and data collection techniques that assist the study of experiential consumption from an embodied and corporeal perspective.
A case-based generalizable theory of consumer collecting
Authors: Saridakis Charalampos , Angelidou Sofia
Published: January 2018

Purpose

Collecting behaviour is a special type of consumption, which consists of several traits, such as “completion”, “perfection”, “caring” and “cooperation”. The purpose of this study is to shed light on this complex consumption behaviour, by effectively developing an empirical typology of collectors and explaining their motivation to engage in collecting.

Design/methodology/approach

In total, 208 questionnaires were collected among Thai collectors. A set-theoretic comparative approach was implemented – namely, fuzzy-set qualitative comparative analysis. The value of the proposed approach over conventional correlational methods, is illustrated through an examination of a set of relevant research propositions.

Findings

The study develops an empirical typology of collectors, on the basis of the various collecting behaviour traits. It has been suggested that different combinations of motives are sufficient for identifying collector types accurately, and the proposed typology is stable and generalizable across collectors of different demographic characteristics. Specifically, “expert professionals” are mainly driven by adventure and social motives, while the role of idea motive is crucial for “introvert focusers”. Adventure and social motives are necessary conditions for “extrovert altruists”, while gratification has a deleterious role. The presence of social motive is necessary for “hobbyists”, while the absence of value motive is also required.

Practical implications

The brand collectible market is booming, and the collectibles can be a strategy for brands to maintain existing users and reinforce loyalty levels. Global brands, such as Swatch and Coca-Cola, have been acquired for collection rather than typical consumption purposes. Marketers and brand managers should therefore monitor the motivation behind this complex consumption behaviour. The mosaic of motives to engage in collecting behaviour varies across different types of collectors, and therefore specifically tailored strategies are proposed.

Originality/value

The study tackles the lack of literature specifically focussing on collecting behaviour in relation to motivation. This is the first attempt to empirically derive a collectors’ typology and provide a nuanced coverage of how financial and nonfinancial (hedonic) motives and their combinations affect different collector types.
Influence of aggregated ratings on purchase decisions: an event-related potential study
Authors: Shen Yongchao , Shan Wei , Luan Jing
Published: January 2018

Purpose

In an online shopping environment, individual reviews and aggregated ratings are important anchors for consumers’ purchasing decisions. However, few studies have considered the influence of aggregated ratings on consumer decision-making, especially at the neural level. This study aims to bridge this gap by investigating the consumer decision-making mechanism based on aggregated ratings to uncover the underlying neural basis and psychological processing.

Design/methodology/approach

An event-related potential experiment was designed to acquire consumers’ electrophysiological records and behavioral data during their decision-making processes based on aggregated ratings. The authors speculate that during this process, review valence categorization (RVC) processing occurs, which is indicated by late positive potential (LPP) components.

Findings

Results show that LPP components were elicited successfully, and perceptual review valence can modulate its amplitudes (one-star [negative] and five-star [positive] ratings evoke larger LPP amplitudes than three-star [neutral] ratings). The electroencephalogram data indicate that consumer decision-making processes based on aggregated ratings include an RVC process, and behavioral data show that easier review valence perception makes the purchase decision-making easier.

Originality/value

This study enriches the extant literature on the impact of aggregated ratings on consumer decision-making. It helps understand how aggregated ratings affect consumers’ online shopping decisions, having significant management implications. Moreover, it shows that LPP components can be potentially used by researchers and companies to evaluate and analyze consumer emotion and categorization processing, serving as an important objective physiological indicator of consumer behavior.