bluuebunny/crossref_metadata_2025 huggingface dataset:
Informed Consent for Bedside Procedures in Pediatric and Neonatal ICUs: A Nationwide Survey*
Authors: Arnolds Marin M. , Feltman Dalia M.
Published: April 2019

Objectives:

Primary objectives were to discover current practices of informed consent for bedside procedures in the PICU and neonatal ICU and how trainees learn to obtain consent. We also attempted to gauge if program directors felt that one method of consent was subjectively superior to another in the way it fulfilled established ethical criteria for informed consent.

Design:

An online anonymous survey. Participants were asked about how and by whom informed consent is currently obtained, training practices for fellows, and attitudes about how different consent methods fulfill ethical criteria.

Setting:

All U.S. fellowship programs for neonatology (n = 98) and pediatric critical care (n = 66) in the fall of 2017.

Subjects:

Neonatal and pediatric critical care fellowship program directors.

Interventions:

None.

Measurements and Main Results:

The overall response rate was 50% (82 of 164). The most common method for obtaining consent in both ICU types was via a written, separate (procedure-specific) consent (63% neonatal ICUs, 83% PICUs); least common was verbal consent (8% neonatal ICUs and 6% PICUs). Fellows were reported as obtaining consent most often (91%), followed by mid-level practitioners (71%) and residents (66%). Residents were one-fifth as likely to obtain consent in the PICU as compared with the neonatal ICU. Sixty-three percent of fellowship directors rated their programs as “strong” or “very strong” in preparing trainees to obtain informed consent. Twenty-eight percent of fellowship directors reported no formal training on how to obtain informed consent.

Conclusions:

Most respondents’ ICUs use separate procedure-specific written consents for common bedside procedures, although considerable variability exists. Trainees reportedly most often obtain informed consent for procedures. Although most fellowship directors report their program as strong in preparing trainees to obtain consent, this study reveals areas warranting improvement.
Decision-Making About Intracranial Pressure Monitor Placement in Children With Traumatic Brain Injury*
Authors: Bennett Tellen D. , Marsh Rebekah , Maertens Julie A. , Rutebemberwa Alle , Morris Megan A. , Hankinson Todd C. , Matlock Daniel D.
Published: April 2019

Objectives:

Little is known about how clinicians make the complex decision regarding whether to place an intracranial pressure monitor in children with traumatic brain injury. The objective of this study was to identify the decisional needs of multidisciplinary clinician stakeholders.

Design:

Semi-structured qualitative interviews with clinicians who regularly care for children with traumatic brain injury.

Setting:

One U.S. level I pediatric trauma center.

Subjects:

Twenty-eight clinicians including 17 ICU nurses, advanced practice providers, and physicians and 11 pediatric surgeons and neurosurgeons interviewed between August 2017 and February 2018.

Interventions:

None.

Measurements and Main Results:

Participants had a mean age of 43 years (range, 30–66 yr), mean experience of 10 years (range, 0–30 yr), were 46% female (13/28), and 96% white (27/28). A novel conceptual model emerged that related the difficulty of the decision about intracranial pressure monitor placement (y-axis) with the estimated outcome of the patient (x-axis). This model had a bimodal shape, with the most difficult decisions occurring for patients who 1) had a good opportunity for recovery but whose neurologic examination had not yet normalized or 2) had a low but uncertain likelihood of neurologically functional recovery. Emergent themes included gaps in medical knowledge and information available for decision-making, differences in perspective between clinical specialties, and ethical implications of decision-making about intracranial pressure monitoring. Experienced clinicians described less difficulty with decision-making overall.

Conclusions:

Children with severe traumatic brain injury near perceived transition points along a spectrum of potential for recovery present challenges for decision-making about intracranial pressure monitor placement. Clinician experience and specialty discipline further influence decision-making. These findings will contribute to the design of a multidisciplinary clinical decision support tool for intracranial pressure monitor placement in children with traumatic brain injury.
Role of IV Immunoglobulin in Indian Children With Guillain-Barré Syndrome*
Authors: Kalita Jayantee , Kumar Mritunjai , Misra Usha K.
Published: April 2019

Objectives:

To evaluate the outcome of Indian children with Guillain-Barré syndrome who received IV immunoglobulin compared with those who did not receive any specific therapy.

Design:

Single center, prospective cross-sectional study.

Setting:

Tertiary care neurology teaching hospital.

Patients:

Children (≤ 18 yr old) with Guillain-Barré syndrome were included from a prospectively maintained Guillain-Barré syndrome registry from January 2008 to April 2017. Children were classified into acute inflammatory demyelinating polyradiculoneuropathy, acute motor axonal neuropathy, acute motor-sensory axonal neuropathy, and inexcitable motor nerves based on nerve conduction study.

Interventions:

Out of 138 pediatric Guillain-Barré syndrome, 50 received IV immunoglobulin and another 50 age and peak disability matched controls (who did not receive IV immunoglobulin or plasmapheresis) were selected from the same registry for comparison.

Measurements and Main Results:

Outcome at 3 and 6 months was defined on the basis of a 0–10 Clinical Grading Scale into complete (Clinical Grading Scale < 3), partial (Clinical Grading Scale 3–5), and poor (Clinical Grading Scale > 5) recovery. The primary outcome was proportion of patients with complete recovery at 3 and 6 months in IV immunoglobulin and non-IV immunoglobulin groups. Secondary outcomes included in-hospital deaths, duration of mechanical ventilation, and hospital stay. Subgroup analysis was done in acute motor axonal neuropathy and acute inflammatory demyelinating polyradiculoneuropathy groups. The baseline characteristics were similar except for shorter duration of illness and higher proportion of facial palsy in IV immunoglobulin group. Hospital deaths, duration of mechanical ventilation, hospital stay, and outcome at 3 and 6 months were not different between the two groups. Children with acute motor axonal neuropathy had better recovery at 6 months on IV immunoglobulin (58.3% vs 11.1%; p = 0.03), but not those with acute inflammatory demyelinating polyradiculoneuropathy (58.3% vs 72.2%; p = 0.22). In nonambulatory Guillain-Barré syndrome children, complete recovery at 6 months was similar in IV immunoglobulin and non-IV immunoglobulin group (57.4% vs 57.1%; p = 0.98).

Conclusions:

In Indian children with Guillain-Barré syndrome, the outcome at 6 months in IV immunoglobulin treated group was similar to non-IV immunoglobulin group. Children with acute motor axonal neuropathy responded better to IV immunoglobulin.
Brief Report: Impact of PrEP Training for Family Planning Providers on HIV Prevention Counseling and Patient Interest in PrEP in Atlanta, Georgia
Authors: Sales Jessica M. , Cwiak Carrie , Haddad Lisa B. , Phillips Ashley , Powell Leah , Tamler Ilyssa , Sheth Anandi N.
Published: April 2019

Background:

Safety net family planning (FP) clinics provide vital care for women in high HIV-burden areas and may be ideal pre-exposure prophylaxis (PrEP) delivery sites. Yet, many FP providers lack knowledge about PrEP.

Setting:

Four safety net FP clinics in Atlanta, Georgia.

Methods:

We provided a 1.5-hour PrEP informational training for 28 providers working in these sites. To assess the training's impact on PrEP counseling, we enrolled 500 female patients after training (47% ≤ 28 years; 69% black; 12% Hispanic) and determined their PrEP indication based on CDC guidelines. We conducted a postvisit survey to assess provider counseling and patients' interest in PrEP and acceptance of off-site PrEP referral.

Results:

From pre-training to post-training, provider PrEP knowledge and confidence to identify women who may benefit from PrEP significantly increased. Only 19% of women knew about PrEP before the visit. Among 376 sexually active women, 29% had risk consistent with PrEP indication. Among PrEP-indicated women, 66% reported the provider discussed PrEP, 29% were interested in taking PrEP, but only 18% accepted off-site PrEP referral. Most (76%) were more willing to take PrEP if provided by the FP clinic.

Conclusions:

After a brief PrEP training, most women with HIV-risk indicators received PrEP counseling during their visits. Once counseled, women expressed interest if it were offered at the FP clinic rather than through off-site referral. Findings highlight the potential impact that PrEP capacity building within safety net FP clinics in high HIV-burden areas may have on PrEP scale-up for women.
Targeted Biopsy Validation of Peripheral Zone Prostate Cancer Characterization With Magnetic Resonance Fingerprinting and Diffusion Mapping
Authors: Panda Ananya , O'Connor Gregory , Lo Wei Ching , Jiang Yun , Margevicius Seunghee , Schluchter Mark , Ponsky Lee E. , Gulani Vikas
Published: April 2019

Objective

This study aims for targeted biopsy validation of magnetic resonance fingerprinting (MRF) and diffusion mapping for characterizing peripheral zone (PZ) prostate cancer and noncancers.

Materials and Methods

One hundred four PZ lesions in 85 patients who underwent magnetic resonance imaging were retrospectively analyzed with apparent diffusion coefficient (ADC) mapping, MRF, and targeted biopsy (cognitive or in-gantry). A radiologist blinded to pathology drew regions of interest on targeted lesions and visually normal peripheral zone on MRF and ADC maps. Mean T1, T2, and ADC were analyzed using linear mixed models. Generalized estimating equations logistic regression analyses were used to evaluate T1 and T2 relaxometry combined with ADC in differentiating pathologic groups.

Results

Targeted biopsy revealed 63 cancers (low-grade cancer/Gleason score 6 = 10, clinically significant cancer/Gleason score ≥7 = 53), 15 prostatitis, and 26 negative biopsies. Prostate cancer T1, T2, and ADC (mean ± SD, 1660 ± 270 milliseconds, 56 ± 20 milliseconds, 0.70 × 10−3 ± 0.24 × 10−3 mm2/s) were significantly lower than prostatitis (mean ± SD, 1730 ± 350 milliseconds, 77 ± 36 milliseconds, 1.00 × 10−3 ± 0.30 × 10−3 mm2/s) and negative biopsies (mean ± SD, 1810 ± 250 milliseconds, 71 ± 37 milliseconds, 1.00 × 10−3 ± 0.33 × 10−3 mm2/s). For cancer versus prostatitis, ADC was sensitive and T2 specific with comparable area under curve (AUC; (AUCT2 = 0.71, AUCADC = 0.79, difference between AUCs not significant P = 0.37). T1 + ADC (AUCT1 + ADC = 0.83) provided the best separation between cancer and negative biopsies. Low-grade cancer T2 and ADC (mean ± SD, 75 ± 29 milliseconds, 0.96 × 10−3 ± 0.34 × 10−3 mm2/s) were significantly higher than clinically significant cancers (mean ± SD, 52 ± 16 milliseconds, 0.65 ± 0.18 × 10−3 mm2/s), and T2 + ADC (AUCT2 + ADC = 0.91) provided the best separation.

Conclusions

T1 and T2 relaxometry combined with ADC mapping may be useful for quantitative characterization of prostate cancer grades and differentiating cancer from noncancers for PZ lesions seen on T2-weighted images.
First Experience With 177Lu-PSMA-617 Therapy for Advanced Prostate Cancer in the Netherlands
Authors: van Kalmthout Ludwike , Braat Arthur , Lam Marnix , van Leeuwaarde Rachel , Krijger Gerard , Ververs Tessa , Mehra Niven , Bins Adriaan , Hunting Jarmo , de Keizer Bart
Published: April 2019

Purpose

The present study summarizes the first experience with 177Lu-PSMA-617 (177Lu-PSMA) treatment in metastatic castration-resistant prostate cancer (PCa) in our institution.

Methods

This was an analysis of the first 30 consecutive patients who underwent 177Lu-PSMA therapy. Biochemical response was defined as prostate-specific antigen decrease of 50% or greater. Clinical toxicity was based on standardized physician's report, and biochemical and hematological toxicity was graded according to the Common Toxicity Criteria for Adverse Events (CTCAE) criteria. Clinical response was objectified in terms of severity of pain and usage of analgesics after separate treatment cycles.

Results

Thirty patients with advanced PCa received therapy cycles with 6 GBq 177Lu-PSMA (median, 4; range, 1–6). After the first cycle, usage of analgesics decreased in 45% of the patients. During treatment, maximum prostate-specific antigen decrease was 50% or greater and 90% or greater in 57% and 24% of the patients, respectively. Despite CTCAE grades III and IV anemia occurring in 2 patients (7%), all other newly originated biochemical toxicity was limited to maximum CTCAE grades I and II. Grade II xerostomia occurred in 17% of the patients. During a median follow-up length of 13.7 months (range, 9.8–32.3 months), median overall survival from start of the first therapy cycle was 11.3 months (range, 1.4–32.3 months).

Conclusions

These results confirm the favorable safety and efficacy profile of 177Lu-PSMA, even up to 6 treatment cycles. Therefore, 177Lu-PSMA seems a promising therapeutic strategy for metastatic castration-resistant PCa patients. However, randomized controlled trials are warranted to obtain robust data.
Monoamine Oxidase B Binding of 18F-THK5351 to Visualize Glioblastoma and Associated Gliosis
Authors: Tago Tetsuro , Toyohara Jun , Sengoku Renpei , Murayama Shigeo , Ishii Kenji
Published: April 2019

An 86-year-old woman with cognitive impairment and left hemiparesis underwent 18F-THK5351 PET 4 months before her death. In addition to “normal” off-target binding in the basal ganglia, abnormal accumulation was observed along the pyramidal tract and around the right basal ganglia as ring-shaped uptake that overlapped a gadolinium-enhanced lesion. Postmortem pathological examination revealed that she had glioblastoma multiforme with associated gliosis, in which monoamine oxidase B (MAO-B) activity is increased. In vitro autoradiography of the corresponding lesion demonstrated specific binding of 18F-THK5351, which was blocked by an MAO-B–selective ligand. Thus, 18F-THK5351 PET may reflect glioblastomas and associated gliosis by binding to MAO-B.
68Ga CXCR-4 PET/CT Imaging in an Atypical Case of Extramedullary Plasmacytoma Mimicking as Renal Cell Carcinoma
Authors: Kumar Rajender , Mittal Bhagwant Rai , Sood Apurva , Singh Harmandeep , Shukla Jaya , Nada Ritambra , Rathi Manish
Published: April 2019

Multiple-myeloma (MM) is a malignant plasma cell proliferation disorder and the second most common blood malignancy after non-Hodgkin lymphoma. The chemokine (CXCR-4) receptor analogues are the newer agents being postulated for myeloma imaging and have shown good diagnostic performance. We report a case of plasmacytoma with suspicious renal cell carcinoma, in whom 68Ga CXCR-4 PET/CT revealed tracer-avid lesion in the left perinephric region. PET/CT-guided biopsy from the tracer-avid lesion revealed plasmacytoma. PET/CT-imaging and guided biopsy using 68Ga CXCR4 receptor ligand, proved its usefulness for accurate localization of the culprit lesion and helped in definitive management of the patient.
Pretherapeutic 68Ga-PSMA-617 PET May Indicate the Dosimetry of 177Lu-PSMA-617 and 177Lu-EB-PSMA-617 in Main Organs and Tumor Lesions
Authors: Wang Jingnan , Zang Jie , Wang Hao , Liu Qingxing , Li Fang , Lin Yansong , Huo Li , Jacobson Orit , Niu Gang , Fan Xinrong , Zhu Zhaohui , Chen Xiaoyuan
Published: April 2019

Aim

Combined 68Ga-PSMA-617 PET imaging and 177Lu-PSMA-617 therapy is a precise targeted theranostic approach for patients with metastatic castration-resistant prostate cancer (mCRPC). The purpose of this study was to determine whether pretherapeutic standard uptake value (SUV) in 68Ga-PSMA-617 PET could indicate the effective dose in the main organs and absorbed dose in tumor lesions.

Methods

After institutional review board approval and informed consent, 9 patients with mCRPC were recruited and underwent 68Ga-PSMA-617 PET/CT scans. Five patients received 177Lu-PSMA-617 (1.30–1.42 GBq, 35–38.4 mCi) and then underwent serial whole-body planar imaging and SPECT/CT imaging of both thoracic and abdominal regions at 0.5-, 2-, 24-, 48-, and 72-hour time points. The other 4 patients received 177Lu-EB-PSMA-617 (0.80–1.1 GBq, 21.5–30 mCi) and then underwent the same imaging procedures at 2-, 24-, 72-, 120-, and 168-hour time points. The effective dose in the main organs and the absorbed dose in tumor lesions were calculated. Detailed correlations between the pretherapeutic SUV in 68Ga-PSMA-617 PET and effective dose in the main organs as well as absorbed dose in the tumor lesions were analyzed.

Results

SUV of 68Ga-PSMA-617 PET was moderately correlated with effective dose in main organs (r = 0.610 for 177Lu-PSMA-617, r = 0.743 for 177Lu-EB-PSMA-617, both P < 0.001). SUV of tumor lesions in 68Ga-PSMA-617 PET had high correlation with those in 177Lu-PSMA-617 (r = 0.915, P < 0.001) and moderate correlation with those in 177Lu-EB-PSMA-617 (r = 0.611, P = 0.002).

Conclusions

Pretherapeutic 68Ga-PSMA-617 PET may indicate the dosimetry of 177Lu-PSMA-617 and 177Lu-EB-PSMA-617. Both the effective dose in main organs and absorbed dose in tumor lesions correlate with SUV of 68Ga-PSMA-617 PET. This relationship may help select appropriate candidates for peptide receptor radionuclide therapy. Further investigations of larger cohorts are needed to confirm these initial findings.
False-Positive 68Ga-DOTATATE PET/CT in Active Chronic Prostatitis
Authors: Yilmaz Burcak , Arslan Hilal Serap , Gundogan Cihan , Gunes Mehmet Nuri , Cermik Tevfik Fikret
Published: April 2019

A 66-year-old man with neuroendocrine tumor originating from midgut was referred to 68Ga-DOTATATE PET/CT imaging for restaging postoperatively. No suspicious uptake regarding residual primary tumoral involvement was seen. But there was diffuse high uptake in prostate gland suggestive of prostatitis or secondary primary tumoral lesion. Concurrent prostate-specific antigen level was 5.02 ng/mL (range, 0–4 ng/mL), C-reactive protein level was 8.25 mg/L (range, <5 mg/L), and white blood cell count was 6.83 × 103/μL (range, 3.9–10.9 × 103/μL). Diagnosis of active chronic prostatitis was achieved by core biopsy, which is identified as potential cause for false-positive diffuse uptake on 68Ga-DOTATATE PET/CT.
Management of Major Burns in 37 Casualties of a Colored Powder Explosion
Authors: Chen Hung-Chang , Wu Katie P. , Yen Cheng-I , Hsiao Yen-Chang , Yang Shih-Yi , Yang Jui-Yung , Chang Shu-Yin , Chuang Shiow-Shuh
Published: April 2019

Background

On June 27, 2015, a colored powder explosion occurred in Taiwan. As a result, 499 people were injured, and over 200 people were in critical condition because of severe burns. Forty-nine casualties were transported to the Chang Gung Memorial Hospital.

Methods

We undertook a single-center retrospective observational study using clinical data for 37 patients with major burns with more than 20% total burn surface area (TBSA). We describe the experience of managing patients with acute burn injuries in these patients. Patient-specific data were analyzed and expressed as mean ± standard deviation.

Results

Thirty-seven major burn patients were admitted to our hospital. The mean ± SD age was 22.5 ± 5 years. The mean ± SD TBSA was 48.9% ± 20%. All patients were stabilized within 6 hours after admission, and no patient experienced hypothermia or hypovolemia. We performed 95 debridement procedures and 88 skin grafts. A mean of 5.6 surgeries were performed for each patient. The mean ± SD hospital stay was 62 ± 32 days. The ratio for hospital days/%TBSA was 1.36, and hospital charges/hospital days ratio was US $973 a day for surviving patients. Two mortalities (2/37, 5.4%) were reported: one was related to cardiac insult, and another was caused by sepsis.

Conclusions

We share our experience in managing 37 major burn patients in a colored powder explosion to improve the holistic care in modern mass burn casualties. Aggressive early debridement and skin grafting reduced hospital stay and costs.
Imaging the multiple sclerosis lesion: insights into pathogenesis, progression and repair
Authors: Wang Chenyu Tim , Barnett Michael , Barnett Yael
Published: April 2019

Purpose of review

Focal white matter lesions are the defining pathological and imaging hallmark of the multiple sclerosis. Until recently, elucidation of the pathophysiology of lesion formation, progression and repair has relied on point neuropathological observations. Here, we review current and emerging concepts of the MRI-defined multiple sclerosis lesion phenotype, advanced longitudinal imaging techniques that permit in-vivo exploration of dynamic microstructural change within lesions and emerging MRI measures of lesion repair.

Recent findings

Novel MRI techniques have elucidated dynamic features of the active multiple sclerosis lesion, defined imaging surrogates for chronic active lesions and revealed progressive microstructural change within chronic inactive lesions. Lesion-related anterograde, retrograde and trans-synaptic neurodegenerative mechanisms are being unravelled in vivo through MRI. An array of myelin-imaging techniques have emerged and in some cases have already been integrated into Phase 2 remyelination trials.

MRI has shed new light on dynamic processes that occur over the lifespan of the multiple sclerosis lesion, and reaffirms the critical role of focal pathology as a determinant of disease progression. The development of robust, longitudinal biomarkers of lesion microstructure, such as advanced diffusion imaging, will be especially important as the era of neurorepair trials in multiple sclerosis dawns.
Diagnosis of multiple sclerosis: revisions of the McDonald criteria 2017 – continuity and change
Authors: Hartung Hans-Peter , Graf Jonas , Aktas Orhan , Mares Jan , Barnett Michael H.
Published: April 2019

Purpose of review

The purpose of this review is to describe the new 2017 revisions of the McDonald diagnostic criteria for multiple sclerosis and review first experiences in their application to different patient populations.

Recent findings

The 2017 revisions agreed on by an international expert panel, as the precursors, define criteria needed to fulfill dissemination in time and space in the clinically isolated syndrome after exclusion of alternative diagnoses. One major change is the inclusion of cerebrospinal fluid (CSF) oligoclonal bands as evidence of dissemination in time in a patient with dissemination in space gathered by clinical or magnetic resonance examination. The distinction between asymptomatic and symptomatic lesions in counting for evidence of dissemination in space or time in supra, infratentorial, and spinal cord syndrome has been abandoned. Finally, cortical lesions can be used to demonstrate dissemination in space. Major differential diagnoses, in particular, the still-evolving concept of neuromyelitis optica spectrum disorders and the myelin oligodendrocyte glycoprotein-IgG-related demyelinating central nervous system disorders.

The new 2017 revisions will simplify the application of the MRI criteria for dissemination in space and include CSF findings as evidence for dissemination in time in clinically isolated syndrome.
Current therapeutic landscape in multiple sclerosis: an evolving treatment paradigm
Authors: Cree Bruce A.C. , Mares Jan , Hartung Hans-Peter
Published: April 2019

Purpose of review

To critically assess the current landscape of disease-modifying agents for multiple sclerosis (MS). Treatment algorithms will be discussed and studies for new agents in late development or recently approved are analyzed in terms of their impact on current treatment strategies.

Recent findings

A real-world study from Wales suggests that early initiation of highly effective therapy may provide more benefit that an escalation approach in relapsing MS. A study from the MSBase dataset found evidence that early treatment with highly effective therapies decreased the risk of developing secondary progressive MS. Ocrelizumab is highly efficacious in relapsing MS and in a group of patients with primary progressive MS. Another CD20 directed mAb, ofatumumab, is in phase 3. A large study examining extended interval dosing of natalizumab in an attempt to decrease the risk of developing progressive multifocal leukoencephalopathy is underway. Cladribine and alemtuzumab may work by immune reconstitution. Siponimod was recently approved by United States Federal Drug Administration for relapsing MS and active secondary progressive MS. Other S1P receptor modulators are being studied in phase 3 trials for relapsing MS. Cladribine received FDA approval as treatment for relapsing and active secondary progressive MS. Autologous hematopoetic stem-cell transplantation may be an option for treatment-refractory MS.

Development of disease-modifying agents in MS continues to be successful. Treatment algorithms need to take new developments into account.
Fourth Nerve Palsy Due to Neurocysticercosis
Authors: Hong Bennett Yau-Bun , Bean Andrew , Vickers Aroucha , Cykowski Matthew , Lee Andrew G.
Published: April 2019

Neurocysticercosis is the most common disease of the nervous system caused by a parasite. Ophthalmological manifestations of cysticercosis typically are due to direct intraorbital or intraocular involvement, parenchymal brainstem involvement, or secondary to hydrocephalus or increased intracranial pressure. We describe a patient with a unilateral fourth nerve palsy, a rare presentation of neurocyticercosis.
A backward encoding approach to recover subcortical auditory activity
Authors: Schmidt Fabian , Demarchi Gianpaolo , Geyer Florian , Weisz Nathan
Published: April 2019

1.

Several subcortical nuclei along the auditory pathway are involved in the processing of sounds. One of the most commonly used methods of measuring the activity of these nuclei is the auditory brainstem response (ABR). Due to its low signal-to-noise ratio, ABR’s have to be derived by averaging over thousands of artificial sounds such as clicks or tone bursts. This approach cannot be easily applied to natural listening situations (e.g. speech, music), which limits auditory cognitive neuroscientific studies to investigate mostly cortical processes.

We propose that by training a backward encoding model to reconstruct evoked ABRs from high-density electrophysiological data, spatial filters can be tuned to auditory brainstem activity. Since these filters can be applied (i.e. generalized) to any other data set using the same spatial coverage, this could allow for the estimation of auditory brainstem activity from any continuous sensor level data. In this study, we established a proof-of-concept by using a backward encoding model generated using a click stimulation rate of 30 Hz to predict ABR activity recorded using EEG from an independent measurement using a stimulation rate of 9 Hz. We show that individually predicted and measured ABR’s are highly correlated (r ∼ 0.7). Importantly these predictions are stable even when applying the trained backward encoding model to a low number of trials, mimicking a situation with an unfavorable signal-to-noise ratio. Overall, this work lays the necessary foundation to use this approach in more interesting listening situations.
Taxonomic variability over functional stability in the microbiome of Cystic Fibrosis patients chronically infected by Pseudomonas aeruginosa
Authors: Bacci Giovanni , Taccetti Giovanni , Dolce Daniela , Armanini Federica , Segata Nicola , Di Cesare Francesca , Lucidi Vincenzina , Fiscarelli Ersilia , Morelli Patrizia , Casciaro Rosaria , Negroni Anna , Mengoni Alessio , Bevivino Annamaria
Published: April 2019

Although the cystic fibrosis (CF) lung microbiome has been characterized in several studies, little is still known about the functions harboured by those bacteria, and how they change with disease status and antibiotic treatment. The aim of this study was to investigate the taxonomic and functional temporal dynamics of airways microbiome in a cohort of CF patients. Multiple sputum samples were collected over 15 months from 22 patients with chronic P. aeruginosa infection, for a total of 79 samples. DNA extracted from samples was subjected to shotgun metagenomic sequencing allowing either strain-level taxonomic profiling and assessment of the functional metagenomic repertoire. High inter-patient taxonomic heterogeneity was found with short-term compositional changes during exacerbations and following antibiotic treatment. Each patient exhibited distinct sputum microbial communities at the taxonomic level, and strain-specific colonization of traditional CF pathogens, including P. aeruginosa, and emerging pathogens. Sputum microbiome was found to be extraordinarily resilient following antibiotic treatment, with rapid recovery of taxa and metagenome-associated gene functions. In particular, a large core set of genes, including antibiotic resistance genes, were shared across patients despite observed differences in clinical status or antibiotic treatment, and constantly detected in the lung microbiome of all subjects independently from known antibiotic exposure, suggesting an overall microbiome-associated functions stability despite taxonomic fluctuations of the communities.

IMPORTANCE

While the dynamics of CF sputum microbial composition were highly patient-specific, the overall sputum metagenome composition was stable, showing a high resilience along time and antibiotic exposure. The high degree of redundancy in the CF lung microbiome could testifies ecological aspects connected to the disease that were never considered so far, as the large core-set of genes shared between patients despite observed differences in clinical status or antibiotic treatment. Investigations on the actual functionality (e.g. by metatranscriptomics) of the identified core-set of genes could provide clues on genetic function of the microbiome to be targeted in future therapeutic treatments.
Streptococcus pyogenescapsule promotes microcolony-independent biofilm formation
Authors: Matysik Artur , Kline Kimberly A.
Published: April 2019

Biofilms play an important role in the pathogenesis of Group A Streptococcus (GAS), a gram-positive pathogen responsible for a wide range infections and significant public health impact. Although most GAS serotypes are able to form biofilms, there is large heterogeneity between individual strains in biofilm formation, as measured by standard crystal violet assays. It is generally accepted that biofilm formation includes initial adhesion of bacterial cells to a surface, followed by microcolony formation, biofilm maturation, and extensive production of extracellular matrix that links together proliferating cells and provides a scaffold for the three-dimensional biofilm structure. However, our studies show that for GAS strain JS95, microcolony formation is not an essential step in static biofilm formation, and instead, biofilm can be effectively formed from slow-growing or non-replicating late exponential or early stationary planktonic cells, via sedimentation and fixation of GAS chains into biofilms. In addition, we show that the GAS capsule specifically contributes to the alternative, sedimentation-initiated biofilms. Microcolony-independent, sedimentation biofilms are similar in morphology and 3-D structure to biofilms initiated by actively dividing planktonic bacteria. We conclude that GAS can form biofilms by an alternate, non-canonical mechanism that does not require transition from microcolony formation to biofilm maturation, and which may be obscured by biofilm phenotypes that arise via the classical biofilm maturation processes.

IMPORTANCE

The static biofilm assay is a common tool for easy biomass quantification of biofilm forming bacteria. However,S. pyogenesbiofilm formation as measured by the static assay is strain dependent and yields heterogeneous results for different strains of the same serotype. In this study, we show that two independent mechanisms, for which the protective capsule contributes opposing functions, may contribute to static biofilm formation. We propose that separation of these mechanisms for biofilm formation might uncover previously unappreciated biofilm phenotypes that may otherwise be masked in the classic static assay.
Robust Reconstruction of CRISPR and Tumor Lineage Using Depth Metrics
Authors: Sugino Ken , Lee Tzumin
Published: April 2019

Lineage reconstruction using CRISPR edited barcodes are becoming wide-spread and methods robust against noise are in need. Neighbor-Joining (NJ) algorithm is a robust distance based algorithm extensively used in phylogeny field. NJ is also used for CRISPR-encoded-lineage (CEL) reconstruction with proper re-rooting since NJ is unrooted algorithm. However, we found NJ works without re-rooting for reconstructing CEL when the lineage contains multiple trees but not for a single tree. Examining why this is the case leads to the idea of “depth metrics”. The notion of depth metrics also naturally explains why Russell-Rao metric, previously found best metric for CEL reconstruction, works well. Furthermore, based on the probabilistic model of CEL, we constructed a new metric that performs better than Russell-Rao metric. We also propose inferring ancestral code during reconstruction instead of using a linkage method. These, together with Nearest-Neighbor-Interchange resulted in a new robust method for reconstructing CEL or tumor-cell-lineages which share same assumptions as CEL.
Transmission of prion infectivity from blood by peptoid-conjugated beads
Authors: Hornemann Simone , Schwarz Petra , Rushing Elisabeth J. , Connolly Michael D. , Zuckermann Ronald N. , Yam Alice Y. , Aguzzi Adriano
Published: April 2019

Prions cause transmissible infectious diseases in humans and animals and have been found to be transmissible by blood transfusion even in the presymptomatic stage. However, the concentration of prions in body fluids such as blood and urine is extremely low, and therefore direct diagnostic tests on such specimens often yield false-negative results. Quantitative preanalytical prion enrichment may significantly improve the sensitivity of prion assays by concentrating trace amounts of prions from large volumes of body fluids. Here we show that beads conjugated to positively charged peptoids not only captured PrP aggregates from plasma of prion-infected hamsters, but also adsorbed prion infectivity in both the symptomatic and preclinical stages of the disease. Bead absorbed prion infectivity efficiently transmitted disease to transgenic indicator mice. We found that the readout of the peptoid-based misfolded protein assay (MPA) correlates closely with prion infectivity in vivo, thereby validating the MPA as a simple, quantitative, and sensitive surrogate indicator of the presence of prions. The reliable and sensitive detection of prions in plasma will enable a wide variety of applications in basic prion research and diagnostics.
Use of an automated pyrosequencing technique for confirmation of Sickle Cell Disease
Authors: Martino CC , Alencar CS , Loureiro P , Carneiro-Proietti AB , Máximo CA , Mota RA , Rodrigues DOW , Gaburo N , Kelly S , Sabino EC ,   for the International Component of the NHLBI Recipient Epidemiology and Donor Evaluation Study (REDS-III)
Published: April 2019

Background

The diagnosis of sickle cell disease (SCD) is made by hemoglobin assays such as high-performance liquid chromatography (HPLC), isoelectric focusing and cellulose acetate or citrate agar electrophoresis. These assays are easy to perform and used in large-scale newborn screening in many countries. These tests however may not easily differentiate Sβ0 thalassemia from SS or identify other hemoglobin variants, and in this case, hemoglobin (HBB) gene sequencing may be necessary.

Objectives

To develop a high throughput DNA based confirmatory assay for SCD and to detect mutations in the HBB gene.

Methods

We developed an automated pyrosequencing technique (PyS) based on QIAGEN technology (Hilden, Germany) to detect homozygous or heterozygous hemoglobin S mutations as well as hemoglobin C mutations. The technique was tested on 2,748 samples from patients enrolled in a multi-center SCD cohort in Brazil. Patients were previously tested using HPLC to diagnose SCD as part of routine clinical care. Any subjects with discrepant results between HPLC and PyS or with heterozygous hemoglobin S detected had Sanger sequencing of the HBB gene.

Results

We identified 168 samples with discrepant results between HPLC and PyS and 100 with concordant HPLC and PyS= heterozygous S, which would suggest Sβ-thalassemia or other hemoglobin S variants. The PyS assay correctly identified 1906 (98.7%) of the 1930 HbSS and 628 (98.7%) of the 636 HbSC samples. Of the 179 remaining samples, PyS correctly indicated S heterozygosis in 165 (92.2%). Of the 165 heterozygous S samples confirmed by Sanger as consistent with Sβ thalassemia genotype, 84 samples were classified as Sβ0 thalassemia and 81 as Sβ+ thalassemia. The most frequent beta thalassemia mutations of Sβ0 and Sβ+ were HBB: c.118C>T (Gln40Stop) and HBB c.92 + 6T> C, respectively.

Discussion

The PyS proved to be satisfactory for large-scale confirmatory testing of hemoglobin mutation. Moreover, with this study we were able to describe the most common β+ and β0 mutations in SCD patients with Sβ-thalassemia in a large multi-institutional SCD cohort in Brazil.
Mck1 defines a key S-phase checkpoint effector in response to various degrees of replication threats
Authors: Li Xiaoli , Jin Xuejiao , Sharma Sushma , Liu Xiaojing , Zhang Jiaxin , Niu Yanling , Li Jiani , Li Zhen , Zhang Jingjing , Cao Qinhong , Liu Beidong , Lou Huiqiang
Published: April 2019

The S-phase checkpoint plays an essential role in regulation of the ribonucleotide reductase (RNR) activity to maintain the dNTP pools. How eukaryotic cells respond appropriately to different levels of replication threats remains elusive. Here, we have identified that a conserved GSK-3 kinase Mck1 cooperates with Dun1 in regulating this process. DeletingMCK1sensitizesdun1Δ to hydroxyurea (HU) reminiscent ofmec1Δ orrad53Δ. As a kinase at the downstream of Rad53, Mck1 does not participate in the post-translational regulation of RNR as Dun1 does, but Mck1 can release the Crt1 repressor from the promoters ofRNR2/3/4by phosphorylation. Meanwhile, Hug1, an Rnr2 inhibitor, is induced to fine-tune the dNTP levels. When cells suffer a more severe threat, Mck1 can inhibit the transcription ofHUG1. Importantly, only a combined deletion ofHUG1andCRT1, can confer a dramatic boost of dNTP levels and the survival ofmck1Δdun1Δ ormec1Δ cells assaulted by a lethal dose of HU. These findings reveal the division-of-labor between Mck1 and Dun1 at the S-phase checkpoint pathway to fine-tune dNTP homeostasis.

Author Summary

The appropriate amount and balance of four dNTPs are crucial for all cells correctly copying and passing on their genetic material generation by generation. Eukaryotes have developed an alert and response system to deal with the disturbance. Here, we uncovered a second-level effector branch. It is activated by the upstream surveillance kinase cascade, which can induce the expression of dNTP-producing enzymes. It can also reduce the inhibitor of these enzymes to further boost their activity according to the degrees of threats. These findings suggest a multi-level response system to guarantee dNTP supply, which is essential to maintain genetic stability under various environmental challenges.
Propane-1,3-diammonium molybdate
Authors: Wane Alioune , Kama Antoine Blaise , Diop Mouhamadou Birame , Diop Libasse , Plasseraud Laurent , Cattey Hélène
Published: April 2019

The reaction between equimolar amounts of propane-1,3-diamine and molybdenum trioxide in water led to the formation of single crystals of the title salt, (C3H12N2)[MoO4]. The asymmetric unit is comprised of one propane-1,3-diammonium cation and one molybdate anion. The latter is isolated in the structure and has a slightly distorted tetrahedral configuration. An extensive network of N—H...O hydrogen bonds connects anions and cations, giving rise to a compact three-dimensional packing.
Tone of earnings announcements in sin industries
Authors: Luo Yan , Zhou Linying
Published: April 2019

Purpose

The purpose of this paper is to investigate the empirical association between the tone of earnings announcements and a company’s membership in a sin industry.

Design/methodology/approach

This study constructs a model of the determinants of earnings announcement tone to examine the impact of sin industry membership on earnings announcement tone. An interaction term between CEO power (CEO–chairman duality) and sin industry membership is used to test whether CEO power moderates the strength of the association. The earnings announcements tone is measured using the spread in the proportion of positive and negative words. The category of sin industry includes not only industries such as tobacco, gambling and alcohol, but also industries associated with emerging environmental, social, and ethical issues (i.e. firearms, oil and cement).

Findings

The analysis of a sample of US firms from the 1994 to 2013 period shows that the tone of earnings announcement is less optimistic for companies in sin industries, but this association is weaker for companies that are led by powerful CEOs. The results remain robust to alternative definitions of sin industry membership and CEO power (CEO tenure) and to alternative model specifications.

Originality/value

The findings suggest that although sin companies cannot change the nature of their business, the management of such companies, in general, uses a less aggressive tone in their earnings announcements. These results further investors’ understanding of sin companies’ reporting behavior.
How cross-culture affects the outcomes of co-creation
Authors: Grott Emily Mary , Cambra-Fierro Jesus , Perez Lourdes , Yani-de-Soriano Mirella
Published: April 2019

Purpose

The aim of this study is two-fold. Firstly, to examine the outcomes of co-creation from a customer perspective using well-recognised customer management variables (customer satisfaction, loyalty and word-of-mouth (WOM). Secondly, to assess potential cross-cultural differences that may exist within the context of co-creation.

Design/methodology/approach

A questionnaire was completed in the banking services industry, and the final valid sample comprised individuals from the UK and Spain. Multi-sample analysis was carried out using PLS software.

Findings

Co-creation has a direct influence on customer satisfaction, customer loyalty and WOM; co-creation activities lead to cumulative customer satisfaction, which also affects customer loyalty and positive WOM. Furthermore, the results show that the direct relationships between co-creation and loyalty and WOM are more powerful for British consumers than Spanish consumers, who need to feel satisfied prior to demonstrating loyalty and engaging in positive WOM.

Practical implications

Firms can use co-creation as a strategic tool if they provide trustworthy collaboration spaces. Furthermore, firms need to adapt the way they interact, listen and respond to customers in different cultural contexts. Trustworthy collaboration spaces and adapting to cultural differences can result in customers who are more satisfied, loyal to the company and more likely to carry out positive WOM, which can ultimately lead to future business.

Originality/value

This study provides insights into co-creation from a customer perspective. Although much service research has examined the drivers of customer co-creation, literature that analyses the consequences of customer co-creation is still scarce. Moreover, this is the first study to provide empirical evidence of cross-cultural differences within the context of co-creation.
Inflation and income inequality in developed and developing countries
Authors: Siami-Namini Sima , Hudson Darren
Published: April 2019

Purpose

The purpose of this paper is to investigate both linear and/or nonlinear effects of inflation on income inequality and to test the Kuznets hypothesis using panel data of 24 developed countries (DCs) and 66 developing countries (LDCs) observed over the period of 1990–2014.

Design/methodology/approach

This paper explores the short- and long-run Granger causality relationship between inflation and income inequality using the Toda and Yamamoto (1995) procedure and a Vector Error Correction Model (VECM) approach. The existence of a nonlinear relationship between inflation and income inequality is confirmed implying as inflation rises income inequality decreases. Income inequality then reaches a minimum and then starts rising again. The findings of this paper show the existence of Kuznets “U-shaped” hypothesis between income inequality and real GDP per capita in DCs group, and the existence of Kuznets’ inverted “U-shaped” hypothesis for LDCs group.

Findings

The results indicate that there is no bi-directional Granger causality between inflation and income inequality in the short-run, but, there is bi-directional Granger causality in the long-run for both the DCs and LDCs group. The results help us to assess the effectiveness of monetary policy in reducing income inequality in both the DCs and LDCs group. As a policy implication, monetary policy is often aimed at controlling the annual rate of inflation in the long-run with a short-run focus on reducing output gaps and creating employment. However, managing inflation may have implications for income inequality.

Originality/value

This is original research paper which analyzes the “U-shaped” and inverted “U-shaped” paths of income inequality and real GDP per capita for large sample of two group countries including developed and developing countries, respectively. Also, this paper analyzes the nonlinear relationship between inflation and income inequality in two groups. Furthermore, this paper investigates the short- and long-run relationship between variables. The results are important for policy makers.
The role of inclusive development and military expenditure in modulating the effect of terrorism on governance
Authors: Asongu Simplice , Nwachukwu Jacinta , le Roux Sara
Published: April 2019

Purpose

The purpose of this paper is to investigate the role of inclusive human development and military expenditure in modulating the effect of terrorism on governance.

Design/methodology/approach

It is based on 53 African countries for the period 1998–2012 and interactive generalised method of moments is employed. Six governance indicators from the World Bank and two terrorism variables are used, namely, domestic and transnational terrorism dynamics.

Findings

The following main findings are established. There is a negative net effect on governance (regulation quality and corruption-control) when inclusive human development is used to reduce terrorism. There is a positive net impact on governance (voice and accountability and rule of law) when military expenditure is used to reduce domestic terrorism.

Originality/value

The authors have complemented the sparse literature on the use of policy variables to mitigate the effect of policy syndromes on macroeconomic outcomes.