bluuebunny/crossref_metadata_2025 huggingface dataset:
Outpatient antibacterial use and costs in children and adolescents: a nationwide register-based study in Finland, 2008–16
Authors: Parviainen Sofia , Saastamoinen Leena , Lauhio Anneli , Sepponen Kati
Published: April 2019

Objectives

To describe the prevalence of outpatient use and the costs of systemic antibacterials among children and adolescents in Finland during 2008–16 and to examine patterns of use by age and gender.

Methods

Data were retrieved from the Finnish statistical database Kelasto, based on the Finnish Prescription Registry. Data included information on dispensed reimbursed prescriptions of antibacterials for systemic use in children aged 0–17 years during 2008–16. The prevalence of antibacterial prescriptions per 1000 children and costs per prescription were calculated.

Results

The overall prevalence of antibacterial prescriptions decreased in the study period and was highest in 2010 (with 708 prescriptions per 1000 children) and lowest in 2016 (with 374 prescriptions per 1000 children). Children aged 1–2 years had the highest prevalence of antibacterial prescriptions. Furthermore, boys had slightly higher prevalences than girls. The 10 most commonly used antibacterial agents covered ∼97% of all prescriptions and broad-spectrum penicillins were the most commonly used antibacterials. The total costs of antibacterials decreased during the study period, but the costs per prescription increased.

Conclusions

This study showed a decreasing trend in the prescribing of antibacterial drugs, regardless of age or gender. Increasing awareness of antimicrobial resistance, reimbursement status changes and pneumococcal and influenza vaccinations are possible reasons for this. Some of the antibacterial oral solutions lost their reimbursement status, but their consumption did not decrease any faster than the consumption of the substances with continuous reimbursability. It is likely that removing the reimbursement status of antibacterials has placed an extra cost burden on families and increased costs per prescription.
Characterization of monoclonal antibodies recognizing each extracellular loop domain of occludin
Authors: Shimizu Yoshimi , Shirasago Yoshitaka , Suzuki Takeru , Hata Tomoyuki , Kondoh Masuo , Hanada Kentaro , Yagi Kiyohito , Fukasawa Masayoshi
Published: April 2019

The tight junction protein occludin (OCLN) is a four-pass transmembrane protein with two extracellular loops (ELs), and also functions as a co-receptor for hepatitis C virus (HCV). Recently, we reported the establishment of monoclonal antibodies (mAbs) recognizing each intact EL domain of OCLN that can strongly prevent HCV infection in vitro and in vivo, and these mAbs were applicable for flow cytometric (FCM) analysis, immunocytochemistry (ICC) and cell-based enzyme-linked immunosorbent assay. In the present study, we further examined the application of these anti-OCLN mAbs and characterized their binding properties. All four mAbs were available for immunoprecipitation. The three first EL (EL1)-recognizing mAbs were applicable for immunoblotting, but the second EL (EL2)-recognizing one was not. Using site-directed mutagenesis, we also determined residues of OCLN critical for recognition by each mAb. Our findings showed that the small loop between two cysteines of the EL2 domain is essential for the binding to one EL2-recognizing mAb and that the recognition regions by three EL1-recognizing mAbs overlap, but are not the same sites of EL1. To obtain a deeper understanding of OCLN biology and its potential as a therapeutic target, specific mAbs to detect or target OCLN in intact cells should be powerful tools for future studies.
Fusarium Crown Rot Whitehead Symptom as Influenced by Wheat Crop Management and Sampling Date
Authors: Smiley Richard W.
Published: April 2019

Symptoms of Fusarium crown rot of wheat include premature death of inflorescens (whiteheads), lesions on subcrown internodes, and rotting of crown tissue and lower stem internodes. Each symptom type is influenced by a different set of environmental conditions. Whiteheads are the easiest symptom to quantify and are frequently reported in the Pacific Northwest U.S.A. The objective of this research was to examine factors associated with whitehead expression and relationships with wheat yield and test weight. Incidence of whiteheads differed for inoculations with different isolates of F. pseudograminearum and F. culmorum, and over years due to weather factors. Whiteheads became less as planting dates for winter wheat were delayed until after September, and incidence was increased with increasing nitrogen application rate. Dates of initial and greatest expression of whiteheads differed among cultivars, which was associated in part with the cultivar heading date. Whiteheads were not correlated with subcrown internode lesions or browning of crown tissue. Whiteheads were also not correlated with grain test weight. Whiteheads were sometimes negatively associated with grain yield, but that relationship was variable and could not be considered a reliable, recurrent, or accurate measure of crown rot severity. These results indicate the need for caution in reporting whiteheads as a sole indicator of cultivar susceptibility to Fusarium crown rot.
Planting a Problem: Examining the Spread of Seed-Borne Potato Virus Y
Authors: Rosenman Jeremy , McIntosh Christopher S. , Aryal Giri Raj , Nolte Phil
Published: April 2019

Potato virus Y (PVY) is among the most economically impactful potato pathogens, yet the spread of PVY from infected seed potatoes within commercial potato fields has not been adequately studied. Test lots containing various seed-borne PVY levels were created by mixing different proportions of seed pieces from healthy and infected tubers drawn from the same seed source. These seed lots were planted in commercial potato fields near the Teton Seed Potato Management Area from 2010 to 2012. Regression analyses on data from these test plots produced models of the in-season spread of PVY originating from infected seed. Conventional ordinary least squares techniques were supplemented with the use of quantile regression; the resulting models indicate the significance of seed-borne PVY on end-of-season infection levels and highlight the need of seed potato buyers to review postharvest testing results.
Management Reasoning: Implications for Health Professions Educators and a Research Agenda
Authors: Cook David A. , Durning Steven J. , Sherbino Jonathan , Gruppen Larry D.
Published: April 2019

Substantial research has illuminated the clinical reasoning processes involved in diagnosis (diagnostic reasoning). Far less is known about the processes entailed in patient management (management reasoning), including decisions about treatment, further testing, follow-up visits, and allocation of limited resources. The authors’ purpose is to articulate key differences between diagnostic and management reasoning, implications for health professions education, and areas of needed research.

Diagnostic reasoning focuses primarily on classification (i.e., assigning meaningful labels to a pattern of symptoms, signs, and test results). Management reasoning involves negotiation of a plan and ongoing monitoring/adjustment of that plan. A diagnosis can usually be established as correct or incorrect, whereas there are typically multiple reasonable management approaches. Patient preferences, clinician attitudes, clinical contexts, and logistical constraints should not influence diagnosis, whereas management nearly always involves prioritization among such factors. Diagnostic classifications do not necessarily require direct patient interaction, whereas management prioritizations require communication and negotiation. Diagnoses can be defined at a single time point (given enough information), whereas management decisions are expected to evolve over time. Finally, management is typically more complex than diagnosis.

Management reasoning may require educational approaches distinct from those used for diagnostic reasoning, including teaching distinct skills (e.g., negotiating with patients, tolerating uncertainty, and monitoring treatment) and developing assessments that account for underlying reasoning processes and multiple acceptable solutions.

Areas of needed research include if and how cognitive processes differ for management and diagnostic reasoning, how and when management reasoning abilities develop, and how to support management reasoning in clinical practice.
Opioids on Trial: A Systematic Review of Interventions for the Treatment and Prevention of Opioid Overdose
Authors: Bahji Anees , Bajaj Neeraj
Published: April 2019

Background:

Canada is in the midst of an opioid epidemic. In 2016, there were more than 2800 apparent opioid-related deaths. Although improved access to naloxone has saved countless lives, it is unclear if there are other effective pharmacological or nonpharmacological interventions for the treatment and prevention of opioid overdose. In this systematic review, we aim to synthesize published findings on such interventions.

Methods:

We searched 5 electronic databases for randomized controlled studies using either pharmacological or nonpharmacological interventions to treat or prevent opioid overdose, and subsequently extracted and synthesized data from appropriate studies.

Results:

Twelve studies met our inclusion criteria. Naloxone, nalmefene, and physostigmine were effective in reversing opioid overdose, whereas naltrexone was effective in preventing opioid overdose. Opioid agonists, including methadone, buprenorphine, and diacetylmorphine, were effective in improving secondary outcomes with variable effects on overdose prevention. No trials using primarily nonpharmacological interventions were identified.

Conclusions:

In this systematic review, naloxone, nalmefene, and physostigmine emerged as effective in treating opioid overdose, whereas naltrexone showed evidence in preventing opioid overdose. Opioid agonists were found to be effective in improving retention in treatment and in reducing illicit opioid use. Pharmacological interventions play a key role in addressing the opioid epidemic; however, evidence for a multidisciplinary approach involving harm reduction and addressing psychosocial barriers could be the topic of subsequent literature reviews.
Functional lateralization in the prefrontal cortex of dopaminergic modulation of memory consolidation
Authors: Papp Mariusz , Gruca Piotr , Lason Magdalena , Niemczyk Monika , Willner Paul
Published: April 2019

There is increasing evidence of functional lateralization within the rat brain. Here, we have examined the lateralization of dopamine (DA) function in the medial prefrontal cortex (PFC) in relation to memory consolidation in the novel object recognition test (NOR). Male Wistar rats received single bilateral or unilateral injections into prelimbic-PFC of agonists (SKF81297; 0.2 µg, quinpirole; 1 µg, SB277,011; 0.5 µg) and antagonists (SCH23390; 3 µg, L-741,626; 1 µg, 7-OH-DPAT; 3 µg) at DA D1, D2, or D3 receptors, immediately following the exposure trial in the NOR, and were tested either 1 or 24 h later for discrimination between a novel and a familiar object. As previously reported, bilateral injection of a D1 antagonist (SCH23390, 3 µg/side), a D2 antagonist (L-741,626, 1 µg/side) or a D3 agonist (7-OH-DPAT, 3 µg/side) impaired NOR at 1 h, while a D1 agonist (SKF81297, 0.2 µg/side), a D2 agonist (quinpirole, 1 µg/side) or a D3 antagonist (SB277,011, 0.5 µg/side) improved NOR at 24 h. The same effects were seen with left-sided unilateral injections. No effects were seen with right-sided unilateral injections. Endogenous DA release in the prelimbic-PFC promotes memory consolidation in the NOR, but only on the left side of the brain.
Corticostriatal Hyperactivation to Reward Presentation in Individuals With TBI With High Depressive Symptomatology: A Pilot Study
Authors: Spirou Angela , Chiaravalloti Nancy D. , Dobryakova Ekaterina
Published: April 2019

Objective:

To examine the impact of depression on neural mechanisms associated with outcome processing (rewarding and punishing outcomes) in persons with traumatic brain injury (TBI).

Setting:

Kessler Foundation's Rocco Ortenzio Neuroimaging Center.

Participants:

A total of 16 adults with moderate to severe TBI.

Main Measures:

Chicago Multiscale Depression Inventory (CMDI); Behavioral Inhibition/Behavioral Activation Scale (BIS/BAS); functional MRI of the head while performing a gambling task, with a reward (+$1.00) and punishment (−$0.50).

Results:

Individuals with TBI reporting high depressive symptomatology exhibited increased activation in the ventromedial prefrontal cortex (VMPFC) and striatum during presentation of rewarding outcomes compared with individuals with TBI reporting low depressive symptomatology. Punishing outcome presentation was not associated with any change in brain activation. No differences in volume of the striatum and VMPFC were observed between groups.

Conclusions:

Current findings provide the first evidence of differences in neural mechanisms underlying outcome processing between individuals with TBI with and without depression. The results suggest that depressive symptomatology might have a different effect on individuals with TBI than what is typically observed in individuals without TBI reporting with depression, with the possibility of rewards becoming more reinforcing as depressive symptomatology increases. Future studies should explore the potential implications of behavioral responses to rewards and punishments in TBI and how they can affect rehabilitation approaches and activities of daily living.
The Relations Among Depression, Cognition, and Brain Volume in Professional Boxers: A Preliminary Examination Using Brief Clinical Measures
Authors: Lee Bern , Bennett Lauren L. , Bernick Charles , Shan Guogen , Banks Sarah J.
Published: April 2019

Objective:

Depression, neuropathology, and cognitive decline are commonly observed with repetitive head injuries (RHIs). We examined whether in boxers (a) clinically significant depression is associated with structural brain changes and cognition; (b) minimal symptoms of depression moderate the relations among RHI and brain volumes and cognition; and (c) baseline depression is associated with longitudinal cognitive changes.

Setting:

Clinical Research Center.

Participants:

A total of 205 male professional boxers.

Design:

Cross-sectional and longitudinal (subsample:n= 45; first visit to follow-up range = 1-6 years; mean = 2.61 years).

Main Measures:

Patient Health Questionnaire-9 depression; CNS Vital Signs cognitive battery; brain imaging.

Results:

Clinically significant depression was associated with smaller regional volumes in insula, cingulate, orbitofrontal cortex, thalami, and middle corpus-callosum subregions; and with poorer verbal memory and psychomotor speed performance. Depression symptoms moderated the relations between RHI and bilateral thalami, left hippocampus, left medial orbitofrontal cortex, and bilateral insula volumes; but not cognition. Baseline depression was associated with poorer psychomotor speed and reaction time longitudinally and improved verbal memory performance longitudinally.

Conclusion:

Clinical depression is associated with volumetric and cognitive changes occasioning RHI exposure, and even minimal depressive symptoms may moderate the relations between exposure and brain volumes in key regions. Longitudinally, there is preliminary evidence that depression precedes cognitive changes.
Acute alcohol effects on conditioned pain modulation, but not temporal summation of pain
Authors: Horn-Hofmann Claudia , Capito Eva Susanne , Wolstein Jörg , Lautenbacher Stefan
Published: April 2019

Although pain reduction after alcohol administration has repeatedly been demonstrated, alcohol effects on advanced and clinically relevant dynamic pain paradigms are still unknown. As such, temporal summation of pain (TSP) and conditioned pain modulation (CPM) indicate mechanisms of endogenous pain modulation and involve certain neurotransmitter systems crucially influenced by alcohol. Our study is the first to investigate acute alcohol effects on TSP and CPM. We investigated 39 healthy subjects in a placebo-controlled within-subject design and targeted alcohol levels of 0.06% (dose 1) and 0.08% (dose 2). Pain threshold, TSP, and CPM were evaluated before and after an alcoholic or placebo drink. Temporal summation of pain was assessed as enhanced pain response to 5 repetitive contact heat stimuli (threshold +3°C). Conditioned pain modulation was tested as pain inhibition when a conditioning stimulus (46°C hot water) was applied concurrently to a test stimulus (contact heat; threshold + 3°C). Both alcohol doses boosted CPM, with a greater effect size for the higher dose. Conditioning stimulus ratings increased after alcohol intake but were not correlated with CPM, suggesting independence of these effects. Temporal summation of pain was not affected by alcohol, and alcohol effects on pain threshold were small and limited to the higher dose. Our findings suggest that analgesic alcohol effects might be mainly driven by an enhancement of endogenous pain inhibition. The frequent use of alcohol as self-medication in chronic pain might be motivated by alcohol temporarily restoring deficient CPM, thus leading to pain relief in the short run and alcohol-related problems in the long run.
Surgical Management of Gynecomastia: A Review of the Current Insurance Coverage Criteria
Authors: Rasko Yvonne M. , Rosen Carly , Ngaage Ledibabari M. , AlFadil Sara , Elegbede Adekunle , Ihenatu Chinezi , Nam Arthur J. , Slezak Sheri
Published: April 2019

Background:

Gynecomastia is a common condition that can be corrected with surgical excision of the breast tissue. Unlike the policies available for reduction mammaplasty in women, gynecomastia policies are variable and not based on strong scientific evidence. This study reviews U.S. insurance policies for coverage of gynecomastia surgery and compares these policies to the guidelines put forth by the American Society of Plastic Surgeons.

Methods:

Sixty U.S. insurance companies were selected based on their market share value. Medicare was also evaluated. The policy for each company was identified using a Web-based search or by contacting the company directly. Policies were reviewed to abstract coverage criteria. All information gathered was compared to national recommendations.

Results:

Of the 61 companies evaluated, 38% did not have a well-defined policy for gynecomastia surgery and assessed each request on a case-by-case basis with no defined criteria. The remaining 62% of providers held a defined policy. Companies often required thorough documentation of breast size, body mass index, extent and duration of symptoms, and prior treatments, but requirements varied between insurers. Many of these policies were limited in their coverage, e.g. they would cover tissue excision but not liposuction. Fourteen companies would consider of coverage for patients younger than 18 years.

Conclusions:

Coverage of gynecomastia surgery varies across insurers. Insurance company considerations do not often align with patient concerns and physician recommendations on gynecomastia and its treatment options. Coverage criteria should be reevaluated and universally established, to expand access to care and improve treatment efficiency.
The Effect of Phenazopyridine on Immediate Postoperative Voiding After Prolapse Surgery: A Randomized Controlled Trial
Authors: Sierra Tania , Taylor Danielle L. , Leung Katherine , Hall Cynthia D. , Flynn Michael K.
Published: April 2019

Objectives

The objective of our study was to determine if phenazopyridine reduces void trial (VT) failure rates after prolapse surgery.

Methods

A single-institution randomized controlled trial was conducted comparing a second dose of phenazopyridine 200 mg on postoperative day 1 versus no additional phenazopyridine in women undergoing prolapse surgery. All subjects (including controls) received 200 mg of phenazopyridine preoperatively for ureteral patency verification. The intervention group received a second dose of phenazopyridine 200 mg the morning of postoperative day 1. The primary outcome was assessed using a standardized VT. Secondary outcomes included pain, opioid usage, urinary tract infections, and prolonged or recurrent urinary retention. An intent-to-treat analysis was performed with a χ2 test to compare failure rates between the intervention and control groups.

Results

We enrolled 152 women, and 76 were randomized to each group. There was no difference in VT failures between the 2 groups—34% failed without phenazopyridine on postoperative day 1, and 42% failed with phenazopyridine on postoperative day 1 (P = 0.326). Subject characteristics were similar across both groups. Pain scores immediately before the VT were 3 out of 10 in both groups (P = 0.206), with no difference in opioid consumption (P = 0.750). There were no differences in the rate of urinary tract infections or prolonged or recurrent urinary retention between the groups (P = 0.304 and P = 0.745).

Conclusions

While previous studies suggested an improvement in immediate postoperative voiding with phenazopyridine, our randomized controlled trial does not support this.
Physical Impairment and Access to Kidney Transplantation
Authors: Haugen Christine E. , Agoons Dayawa , Chu Nadia M. , Liyanage Luckimini , Long Jane , Desai Niraj M. , Norman Silas P. , Brennan Daniel C. , Segev Dorry L. , McAdams-DeMarco Mara
Published: April 2019

Background.

The short physical performance battery (SPPB) test is an objective measurement of lower extremity function (walk speed, balance, chair stands). SPPB impairment is associated with longer length of stay and increased mortality in kidney transplant (KT) recipients. Furthermore, the SPPB test may represent an objective quantification of the “foot of the bed test” utilized by clinicians; therefore, impairment may translate with decreased access to KT.

Methods.

We studied 3255 participants (2009–2018) at 2 KT centers. SPPB impairment was defined as a score of ≤10. We estimated time to listing, waitlist mortality, and transplant rate by SPPB impairment status using Cox proportional hazards, competing risks, and Poisson regression.

Results.

The mean age was 54 years (SD = 14; range 18–89) and 54% had SPPB impairment. Impaired participants were less likely to be listed for KT (adjusted hazard ratio: 0.70, 95% CI: 0.64-0.77, P < 0.001). Also, once listed, impaired candidates had a 1.6-fold increased risk of waitlist mortality (adjusted subhazard ratio: 1.56, 95% CI: 1.18-2.06, P = 0.002). Furthermore, impaired candidates were transplanted 16% less frequently (adjusted incidence rate ratio: 0.84, 95% CI: 0.73-0.98, P = 0.02).

Conclusions.

SPPB impairment was highly prevalent in KT candidates. Impaired candidates had decreased chance of listing, increased risk of waitlist mortality, and decreased rate of KT. Identification of robust KT candidates and improvement in lower extremity function are potential ways to improve survival on the waitlist and access to KT.
Prognostic Value of “A” Waves in Patients With Guillain Barre Syndrome
Authors: Badry Reda
Published: April 2019

Introduction:

The “A” wave is a compound action potential evoked consistently from a muscle by submaximal electric stimulation to the nerve. “A” waves were usually associated with the presence of conduction block and abounded in lower limbs more than in upper limbs. Guillain Barre syndrome is an autoimmune polyradiculoneuropathy that usually follows respiratory or gastrointestinal infections.

Purpose:

To study the prognostic value of “A” waves in patients with Guillain Barre syndrome with different recovery patterns.

Methods:

In this study, 50 patients with GuillainBarreSyndrome were enrolled. They were divided into two groups based on the presence or absence of “A” waves in their neurophysiologic study at onset of illness. Strength of limb muscles of the involved patients was assessed at onset of the study and 6 weeks later (short-term clinical recovery) using the Medical Research Council Scale.

Results:

Patients with waves (29 patients: 58%) showed poorer short-term follow-up parameters than those without “A” waves (21 patients: 42%).

Conclusions:

Presence of “A” waves is usually associated with conduction block and marked degree of demyelination. “A” waves carry poor prognostic value in short-term follow-up parameters in patients with Guillain Barre syndrome.
Integrated K+channel and K+-Cl−cotransporter functions regulate fin proportionality in zebrafish
Authors: Lanni Jennifer S. , Peal David , Ekstrom Laura , Chen Haining , Stanclift Caroline , Bowen Margot , Mercado Adriana , Gamba Gerardo , Kahle Kristopher T. , Harris Matthew P.
Published: April 2019

The coordination of growth during development establishes proportionality within and among the different anatomic structures of organisms. Innate memory of this proportionality is preserved, as shown in the ability of regenerating structures to return to their original size. Although the regulation of this coordination is incompletely understood, mutant analyses of zebrafish with long-finned phenotypes have uncovered important roles for bioelectric signaling in modulating growth and size of the fins and barbs. To date, long-finned mutants identified are caused by hypermorphic mutations, leaving unresolved whether such signaling is required for normal development. We isolated a new zebrafish mutant,schleier, with proportional overgrowth phenotypes caused by a missense mutation and loss of function in the K+-Cl−cotransporter Kcc4a. Genetic depletion of Kcc4a in wild-type fish leads to a dose-dependent loss of growth restriction in fins and barbs, supporting a requirement for Kcc4a in regulation of proportion. Epistasis experiments suggest that Kcc4a and the two-pore potassium channel Kcnk5b both contribute to a common bioelectrical signaling response in the fin. These data suggest that an integrated bioelectric signaling pathway is required for the coordination of size and proportion during development.

Graphical Abstract
Choice of Contact Points Modulates Sensorimotor Cortical Interactions for Dexterous Manipulation
Authors: Parikh Pranav J. , Fine Justin M. , Santello Marco
Published: April 2019

Humans are unique in their ability to perform dexterous object manipulation in a wide variety of scenarios. However, previous work has used a grasping context that predominantly elicits memory-based control of digit forces by constraining where the object should be grasped. For this ‘constrained’ grasping context, primary motor cortex (M1) is involved in storage and retrieval of digit forces used in previous manipulations. In contrast, when choice of digit contact points is allowed (‘unconstrained’ grasping), behavioral studies revealed that forces are adjusted, on a trial-to-trial basis, as a function of digit position. This suggests a role of online feedback that detects digit position, rather than memory, for force control. However, despite the ubiquitous nature of unconstrained hand-object interactions in activities of daily living, the underlying neural mechanisms are unknown. Using non-invasive brain stimulation and electroencephalography, we found the role of M1 to be sensitive to grasping condition. While confirming the role of M1 in storing and retrieving learned digit forces and position in ‘constrained’ grasping, we also found that M1 is involved in modulating digit forces to digit position in unconstrained grasping. Furthermore, we found that digit force modulation to position relies on sensorimotor integration mediated by primary sensory cortex (S1) and M1. This finding supports the notion of a greater contribution of somatosensory feedback of digit position in unconstrained grasping. We conclude that the relative contribution of memory and online feedback based on whether contact points are constrained or unconstrained modulates sensorimotor cortical interactions for dexterous manipulation.
The preparation of cyclopentadecanone and cyclopentadecanolide from Malania oleifera Chum oil
Authors: Liu Pin , Liu Xiongmin , Lai Fang , Ma Li , Li Weiguang , Huang Pinxian
Published: April 2019

The macrocyclic musks are of central importance in the fragrance industry. The preparation of cyclopentadecanone and cyclopentadecanolide from Malania oleifera Chum oil were investigated. Preparation method of cyclopentadecanone is three steps process: first fatty acid double bonds of Malania oleifera Chum oil are cut off by ozonolysis; second ozonides are converted into methyl esters by esterification; afterwards cyclopentadecanone was achieved from through acyloin condensation, reduction and separation with 38.5 % overall yield. The preparation coyfclopentadecanolide is two step process: first by ozonolysis triglycerides of ω-hydroxycarboxylic acids synthesized from malania oleifera chum oil by ozonolysis; and it were catalytically transformed to macrocyctic lactones, and a 63% yield of cyclopentadecanolide was obtained. The effect of different ester groups on cyclization of α,ω-difatty acid alkyl ester, and effect of catalysts on cyclization of ω-hydroxycarboxylic acid triglyceride were investigated.
SwissFEL Aramis beamline photon diagnostics. Erratum
Authors: Juranić Pavle , Rehanek Jens , Arrell Christopher A. , Pradervand Claude , Cassar Ariana , Calvi Marco , Ischebeck Rasmus , Erny Christian , Heimgartner Peter , Gorgisyan Ishkhan , Thominet Vincent , Tiedtke Kai , Sorokin Andrey , Follath Rolf , Makita Mikako , Seniutinas Gediminas , David Christian , Milne Christopher J. , Lemke Henrik , Radovic Milan , Hauri Christoph P. , Patthey Luc
Published: April 2019

The list of authors in the paper by Juranić et al. (2018) [J. Synchrotron Rad.
25, 1238–1248] is corrected.
Structural and functional insights into phosphomannose isomerase: the role of zinc and catalytic residues
Authors: Bangera Mamata , Gowda K Giri , Sagurthi S. R. , Murthy M. R. N.
Published: April 2019

Phosphomannose isomerase (PMI) is a housekeeping enzyme that is found in organisms ranging from bacteria to fungi to mammals and is important for cell-wall synthesis, viability and signalling. PMI is a zinc-dependent enzyme that catalyses the reversible isomerization between mannose 6-phosphate (M6P) and fructose 6-phosphate (F6P), presumably via the formation of acis-enediol intermediate. The reaction is hypothesized to involve ring opening of M6P, the transfer of a proton from the C2 atom to the C1 atom and between the O1 and O2 atoms of the substrate, followed by ring closure resulting in the product F6P. Several attempts have been made to decipher the role of zinc ions and various residues in the catalytic function of PMI. However, there is no consensus on the catalytic base and the mechanism of the reaction catalyzed by the enzyme. In the present study, based on the structure of PMI fromSalmonella typhimurium, site-directed mutagenesis targeting residues close to the bound metal ion and activity studies on the mutants, zinc ions were shown to be crucial for substrate binding. These studies also suggest Lys86 as the most probable catalytic base abstracting the proton in the isomerization reaction. Plausible roles for the highly conserved residues Lys132 and Arg274 could also be discerned based on comparison of the crystal structures of wild-type and mutant PMIs. PMIs from prokaryotes possess a low sequence identity to the human enzyme, ranging between 30% and 40%. Since PMI is important for the virulence of many pathogenic organisms, the identification of catalytically important residues will facilitate its use as a potential antimicrobial drug target.
The politics of development in Palau
Authors: Thomas Erin
Published: April 2019

Purpose

The Republic of Palau in the Micronesian region of the Pacific illuminates the complexities of how the political geography of development is shaped through diplomacy, defense and migration policy. The Compact of Free Association (COFA) between Palau and the US has been a topic of debate and for some resistance.

Design/methodology/approach

Through discursive analysis of grey literature and post-development and political geography frameworks, this paper analyzes the way in which development, through unconventional pathways, is used to exert power by Palau’s largest donor, the US.

Findings

The donor–recipient, government-to-government framework fails to explore the ways in development is used as power through military operations, zonal capitalism, redefined citizenship and tourism as new aid modalities. These graduated sovereignties in Palau show that political geography is taking shape through new pathways of development, which has resulted in more actors, institutions and discourses.

Originality/value

With limited research on the region of Micronesia and particularly the politics of development, this paper contributes important analysis to the lead up to the COFA renewal negotiations between the US and Palau in 2024.
The strong, the weak and the meaningful
Authors: Patulny Roger , Ramia Gaby , Feng Zhuqin , Peterie Michelle , Marston Greg
Published: April 2019

Purpose

Governments increasingly promote employment through social networks (whether via formal job networks or informal personal networks). However, they rarely account for how weak-tie “bridging” networks and strong-tie “bonding” networks differentially affect employment outcomes. Given criticism that (usually weak-tie bridging-focussed) formal job networks are overly focussed on finding entry-level (i.e. any) jobs, it is imperative to understand the impact of strong and weak ties on securing work with good conditions, or of meaning to the worker. Such links are poorly understood in the present literature. The paper aims to discuss this issue.

Design/methodology/approach

This study uses national Australian survey data to assess whether support from close “friends” or distant “acquaintances” is associated with employment outcomes such as finding any work or “meaningful” work.

Findings

The results show that relatively distant ties (close acquaintances) and emotional support from friends are each associated with reduced chances of being an unemployed/discouraged worker. Stronger ties (close friends) are associated with better chances of a having a “meaningful” job.

Practical implications

More attention should be paid to tie strength dynamics and meaningful employment outcomes in the delivery of employment services. In particular, a role for active “close-tie brokers” in promoting networks should be investigated, instead of expecting/pushing the unemployed to rely on either extremely close or distant connections.

Originality/value

This is the first study to find a link between network type and meaningful work, which has important implications for the delivery of employment services.
Next generation engagement: Setting a research agenda for community engagement in Australia's infrastructure sector
Authors: Bice Sara , Neely Kate , Einfeld Colette
Published: April 2019

The global infrastructure sector is thriving. But community opposition to major projects is also rising. Australian examples demonstrate the policy backflips, reputational pitfalls, and financial costs of project delays and cancellations. Failures to engage communities are surprising, given the widespread adoption of community engagement (CE) principles and the increasing professionalization of CE roles. If acceptance of the need for CE in infrastructure is more widespread than ever, why are we not seeing smoother project delivery, reduced protest, and cost savings? This paradox is the driving force behind the Next Generation Engagement project. This article offers a practitioners’ perspective to introduce the project and present key findings from its 12‐month pilot study aiming to establish a transdisciplinary, industry‐led research agenda for CE in Australia's infrastructure sector. The article contributes to our understanding of CE literature and research codesign. It maps out the top five priority themes for future research to support infrastructure selection, planning and delivery. The research agenda provides guidance for policy, and practice, offering consolidated, research‐based insights for policymakers and practitioners.
Phase I/II Pilot Study of Wilms' Tumor 1 Peptide‐Pulsed Dendritic Cell Vaccination Combined With Conventional Chemotherapy in Patients With Head and Neck Cancer
Authors: Ogasawara Masahiro , Miyashita Mamiko , Yamagishi Yuka , Ota Shuichi
Published: April 2019

The prognosis of metastatic or relapsed head and neck squamous cell carcinoma (HNSCC) remains poor despite the introduction of immune checkpoint blockade agents. We aimed to investigate the safety and the feasibility of a vaccination with Wilms' tumor 1 peptide‐loaded dendritic cells (DCs) and OK‐432 adjuvant combined with conventional chemotherapy. Eleven eligible patients with metastatic or relapsed HNSCC were enrolled. No severe adverse events related to a vaccination were observed. Five patients had durable stable disease and six other patients had disease progression after DC vaccination. Median progression‐free survival and overall survival was 6.4 months and 12.1 months, respectively. DC vaccination augmented Wilms' tumor 1‐specific immunity which might be related to clinical outcome. These results indicate that DC‐based immunotherapy combined with a conventional chemotherapy is safe and feasible for patients in advanced stage of HNSCC.
Evaluating a 24‐year tuberculosis screening in first‐grade elementary schoolers in a low‐burden area
Authors: Trachanatzi E , Ladomenou F , Galanakis E
Published: April 2019

Aim

Early diagnosis of tuberculosis infection can significantly contribute to the control of the disease. The aim of the present study was to describe the tuberculin skin test (TST) trends over a 24‐year period (1990–2013) and explore the value of universal tuberculosis screening in a low‐burden area.

Methods

All first graders that underwent TST during the 24‐year study period (1990–2013) on the island of Crete, Greece, were retrospectively included in the study.

Results

A total of 82 402 children (92.3% of Greek nationality; 51.0% male) underwent TST, of whom 335 (0.41%, 95% CI 0.37–0.46) were found to have positive TST while 0.27% of the study population had a TST between 5 and 9 mm. The tuberculin index declined significantly between 1990–1994 and 2010–2013 (0.67 vs 0.26; RR 2.73, 95% CI 1.82–4.09; p < 0.0001). Positive TST result was significantly higher in the immigrant than the native group (0.66% vs 0.24%; RR 3.76 95%, CI 2.89–4.84; p < 0.0001). In the last study years, 386 children (488 native; 153 immigrant) should be tested for one to be found TST positive.

Conclusion

Our findings question the massive tuberculin testing in low‐burden areas and point to selective screening of high‐risk groups.
The Resilient Organisation: A Meta‐Analysis of the Effect of Communication on Team Diversity and Team Performance
Authors: Bui Hong , Chau Vinh Sum , Degl'Innocenti Marta , Leone Ludovica , Vicentini Francesca
Published: April 2019

The Input‐Process‐Output framework is adopted to examine the impact of diversity attributes (the input) on communication (the process) and their influence on performance (the output), to understand the internal group/team working mechanisms of organisational resilience. A meta‐analysis of 174 correlations from 35 empirical studies undertaken over 35 years (1982–2017) showed that members of a team who have different experiences are more likely to share information and communicate openly when they deal with a task that requires collaboration outside the team. This supports the view that organisations are more resilient by being more closely connected with the external environment. Differences in social categories tend to favour openness of communication, especially in the case of age diversity and race/ethnicity diversity. An increase in openness of communication is likely to enhance team performance, particularly for small and medium‐sized teams operating in manufacturing industries, while frequency of communication can be beneficial for both large and medium‐sized teams working in the high technology industry. The positive workings of these associations form the resilient organisation.
Efficacious dose of metformin for breast cancer therapy is determined by cation transporter expression in tumours
Authors: Cai Hao , Everett Ruth S. , Thakker Dhiren R.
Published: April 2019

Background and Purpose

It has been extensively reported that the leading anti‐diabetic drug, metformin, exerts significant anticancer effects. This hydrophilic, cationic drug requires cation transporters for cellular entry where it activates its intracellular target, the AMPK signalling pathway. However, clinical results on metformin therapy (used at antidiabetic doses) for breast cancer are ambiguous. It is likely that the antidiabetic dose is inadequate in patients that have breast tumours with low cation transporter expression, resulting in non‐responsiveness to the drug. We postulate that cation transporter expression and metformin dose are key determinants in its antitumour efficacy in breast cancer.

Experimental Approach

Antitumour efficacy of metformin was compared between low cation transporter‐expressing MCF‐7 breast tumours and MCF‐7 tumours overexpressing organic cation transporter 3 (OCT3‐MCF7). A dose–response relationship of metformin in combination with standard‐of‐care paclitaxel (for oestrogen receptor‐positive MCF‐7 breast tumours) or carboplatin (for triple‐negative MDA‐MB‐468 breast tumours) was investigated in xenograft mice.

Key Results

Metformin had greater efficacy against tumours with higher cation transporter expression, as observed in OCT3‐MCF7 versus MCF‐7 tumours and MDA‐MB‐468 versus MCF‐7 tumours. In MCF‐7 tumours, a threefold higher metformin dose was required to achieve intratumoural exposure that was comparable to exposure in MDA‐MB‐468 tumours and enhance antitumour efficacy of standard‐of‐care in MCF‐7 tumours versus MDA‐MB‐468 tumours. Antitumour efficacy correlated with intratumoural AMPK activation and metformin concentration.

Conclusions and Implications

An efficacious metformin dose for breast cancer varies among tumour subtypes based on cation transporter expression, which provides a useful guide for dose selection.
The thickness of labial bone affects the esthetics of immediate implant placement and provisionalization in the esthetic zone: A prospective cohort study
Authors: Yang Xingmei , Zhou Tengfei , Zhou Nan , Man Yi
Published: April 2019

Background

A 1‐2 mm thick labial plate is generally advocated in immediate implant placement and provisionalization (IIPP). However, most of the human labial plates fail to meet this requirement.

Purpose

This study aimed to investigate the effect of labial plate thickness on hard tissue, soft tissue, and esthetic outcomes in IIPP.

Materials and Methods

In this prospective cohort study, 40 patients received IIPP of 50 single‐crown implants in the anterior maxilla. Patients were categorized into three groups according to their presurgical thickness of labial bone: 0‐0.5, 0.5‐1, and ≥ 1 mm. CBCT, mucosa recession and the papilla index were used to analyze labial hard and soft tissue alterations with a 1‐year follow‐up.

Results

At 1 year, OCI bone losses were 1.17 ± 0.73, 0.37 ± 0.39, 0.46 ± 0.35 mm; ICH bone losses were 2.23 ± 1.83, 0.74 ± 0.71, 0.72 ± 1.27 mm; TM recessions were 1.00 ± 0.51, −0.06 ± 0.37, −0.30 ± 0.88 mm; TL recessions were 0.61 ± 1.02, −0.18 ± 0.40, −0.26 ± 1.15 mm; TD recessions were 0.61 ± 1.02, −0.18 ± 0.40, −0.26 ± 1.15 mm; PIS scores were 1.63 ± 0.64, 2.20 ± 0.71, 2.71 ± 0.57 in group 0‐0.5, 0.5‐1 and ≥ 1 mm, respectively. No statistical significance was found between group 0.5‐1 and ≥ 1 mm in bone resorption, gingival recession, and papilla index. The bone resorption and gingival recession were significantly the highest in group 0‐0.5 mm at 6 months and 1 year.

Conclusions

Group 0.5‐1 mm had similar tissue dimensional alteration as group ≥1 mm, while group <0.5 mm suffered more massive bone resorption and gingival recession. Concerning the thickness of the labial plate, this study may suggest an expansion in the indication of IIPP.
Biological width establishment around dental implants is influenced by abutment height irrespective of vertical mucosal thickness: A cluster randomized controlled trial
Authors: Spinato Sergio , Stacchi Claudio , Lombardi Teresa , Bernardello Fabio , Messina Marcello , Zaffe Davide
Published: April 2019

Objective

Prosthetic abutment height and peri‐implant mucosal thickness are considered factors that influence marginal bone remodeling during biological width establishment around dental implants. However, no clinical studies have evaluated their simultaneous effect on marginal bone loss (MBL). This study analyzes the influence of abutment height on MBL around implants surrounded by both thin and thick mucosa up to 12 months after prosthetic loading.

Material and methods

Seventy platform‐switched implants with internal hex were placed equicrestally in two groups of patients with different vertical mucosal thickness: thin (≤2.0 mm) and thick mucosa (>2.0 mm). After three months of submerged healing, prosthetic abutments with a height of 1 mm (short) or 3 mm (long) were randomly assigned for single crown screwed restoration in both groups. MBL was evaluated on radiographs taken at implant placement (T0), restoration delivery (T1), and after 6 months (T2) and 12 months (T3) of loading.

Results

After 12 months of loading, 66 implants were functioning (two dropouts, two failures), resulting in a 97% survival rate. Compared with T0, mean MBL at T3 ranged between 0.59 and 0.80 mm in short abutment groups and between 0.28 and 0.37 mm in long abutment groups. Differences resulted statistically significant, irrespective of vertical peri‐implant mucosal thickness. The MBL pattern over time showed the greatest amount of bone resorption in the first 6 months after loading, particularly around implants with short abutments.

Conclusions

Platform‐switched implants restored with short abutments present greater marginal bone loss than identical implants with long abutments, without significant peri‐implant mucosal thickness effects.
Allochrony as a potential driver for reproductive isolation in adaptive radiations of European whitefish ecomorphs
Authors: Bitz‐Thorsen Julie , Häkli Katja , Bhat Shripathi , Præbel Kim
Published: April 2019

In northern Fennoscandian lakes, monophylogenetic lineages of postglacial fishes are radiating into several adaptive forms, but the speciation process is still at an incipient stage. The speciation process has received increased attention over the years, but the underlying mechanisms and drivers are still debated and poorly understood. European whitefish (Coregonus lavaretus[L.]) is the most abundant fish species in these lakes and has evolved into several ecomorphs adapted to different trophic niches and habitats. Genetic divergence has been observed among these ecomorphs, but the mechanism(s) responsible for the ongoing build‐up of reproductive isolation has still to be revealed. As these systems are young in evolutionary time (<10 kyr), prezygotic and postzygotic extrinsic isolation mechanisms are thought to be more likely to contribute to the reproductive isolation than intrinsic isolation mechanisms. We determined the gonadosomatic index (GSI) of three ecomorphs in two replicated lake systems and used GSI as a proxy to investigate the prezygotic isolation mechanism, allochrony, as a driving factor of divergence in this adaptive radiation of whitefish. We found that the three ecomorphs differed in GSI values within and between lakes, suggesting different spawning times of the ecomorphs. We also show that males of one ecomorph had equal onset of maturity as another ecomorph, giving novel insights into the ongoing gene flow observed between ecomorphs. The result supports allochrony as a driver for the divergence process of whitefish ecomorphs, but more evidence is still needed to rule out that the three ecomorphs make use of different spawning grounds.