bluuebunny/crossref_metadata_2025 huggingface dataset:
Study of charge transport properties in a ZnO/CdS/Cu(In,Ga)Se2 solar cell via admittance spectroscopy
Authors: Paul Sanjoy , Lopez Roberto , Repins Ingrid L. , Li Jian V.
Published: February 2018

The authors investigate the charge carrier transport properties in a thin-film heterojunction Cu(In,Ga)Se2 (CIGS) solar cell device via coordinated capacitance–voltage and admittance spectroscopic measurements. The CIGS absorber width was measured using temperature dependent depletion width in the freeze-out regime and its acceptor density extracted from conventional capacitance–voltage analysis in the non-freeze-out regime. The bias-dependent modified dielectric relaxation in the Cu(In,Ga)Se2 solar cell was exploited to extract the absorber's resistivity, hole mobility, and their temperature dependency, all by admittance spectroscopy. In the temperature range of 133–300 K, the extracted hole mobility in the CIGS device increases from 7.55 × 10−3 to 4.08 cm2/V s with temperature. The temperature dependent resistivity and mobility show Arrhenius behavior with an activation energy ≈120 meV. The thermally activated behavior of mobility is related to the potential fluctuation encountered by the holes during their transport, which enables admittance spectroscopy to directly measure the potential fluctuation in the CIGS polycrystalline material.
(A)GO for gene expression
Authors: Ferrarelli Leslie K.
Published: February 2018

AGO1 promotes, rather than represses, gene expression in response to hormones and stress signaling in plants by binding chromatin.
Coexistence of Two
bla
NDM-5
Genes on an IncF Plasmid as Revealed by Nanopore Sequencing
Authors: Feng Yu , Liu Lu , McNally Alan , Zong Zhiyong
Published: February 2018

In a carbapenem-resistant
Escherichia coli
clinical isolate of sequence type 167, two copies of
bla
NDM-5
were found on a 144,225-bp IncF self-transmissible plasmid of the F36:A4:B
−
type. Both
bla
NDM-5
genes were located in 11,065-bp regions flanked by two copies of IS
26
. The two regions were identical in sequence but were present at different locations on the plasmid, suggesting a duplication of the same region. This study highlights the complex genetic contexts of
bla
NDM-5
.
Inactivation of Plasmepsins 2 and 3 Sensitizes Plasmodium falciparum to the Antimalarial Drug Piperaquine
Authors: Mukherjee Angana , Gagnon Dominic , Wirth Dyann F. , Richard Dave
Published: February 2018

Dihydroartemisinin-piperaquine (DHA-PPQ), the current frontline artemisinin combination therapy used to treat
Plasmodium falciparum
malaria in multiple Southeast Asian countries, is now increasingly failing in Cambodia, where artemisinin resistance is nearly fixed, which suggests that PPQ resistance has emerged and is spreading rapidly in the Greater Mekong Subregion. Recent reports have shown that amplification of the genes encoding plasmepsins 2 and 3 is a molecular marker of PPQ resistance; however, whether these enzymes play a role in the mechanism of resistance is currently unknown. We show here that inactivating the genes encoding plasmepsin 2 or 3 individually in
P. falciparum
reference strain 3D7 results in hypersusceptibility to PPQ. Interestingly, no significant differences in the susceptibility to other antimalarials were observed, which suggests specific roles of plasmepsins 2 and 3 in PPQ susceptibility. The piperaquine hyper-sensitivity of the plasmepsin-2-and-3-inactivated lines provides direct evidence that these enzymes modulate parasite susceptibility to PPQ in the context of a single copy of
PfMDR1
and independent of Kelch13 mutations conferring artemisinin resistance.
Metagenomics Reveals the Impact of Wastewater Treatment Plants on the Dispersal of Microorganisms and Genes in Aquatic Sediments
Authors: Chu Binh T. T. , Petrovich Morgan L. , Chaudhary Adit , Wright Dorothy , Murphy Brian , Wells George , Poretsky Rachel
Published: February 2018

Wastewater treatment plants (WWTPs) release treated effluent containing mobile genetic elements (MGEs), antibiotic resistance genes (ARGs), and microorganisms into the environment, yet little is known about their influence on nearby microbial communities and the retention of these factors in receiving water bodies. Our research aimed to characterize the genes and organisms from two different WWTPs that discharge into Lake Michigan, as well as from surrounding lake sediments to determine the dispersal and fate of these factors with respect to distance from the effluent outfall. Shotgun metagenomics coupled to distance-decay analyses showed a higher abundance of genes identical to those in WWTP effluent genes in sediments closer to outfall sites than in sediments farther away, indicating their possible WWTP origin. We also found genes attributed to organisms, such as those belonging to
Helicobacteraceae
,
Legionellaceae
,
Moraxellaceae
, and
Neisseriaceae
, in effluent from both WWTPs and decreasing in abundance in lake sediments with increased distance from WWTPs. Moreover, our results showed that the WWTPs likely influence the ARG composition in lake sediments close to the effluent discharge. Many of these ARGs were located on MGEs in both the effluent and sediment samples, indicating a relatively broad propensity for horizontal gene transfer (HGT). Our approach allowed us to specifically link genes to organisms and their genetic context, providing insight into WWTP impacts on natural microbial communities. Overall, our results suggest a substantial influence of wastewater effluent on gene content and microbial community structure in the sediments of receiving water bodies.

IMPORTANCE
Wastewater treatment plants (WWTPs) release their effluent into aquatic environments. Although treated, effluent retains many genes and microorganisms that have the potential to influence the receiving water in ways that are poorly understood. Here, we tracked the genetic footprint, including genes specific to antibiotic resistance and mobile genetic elements and their associated organisms, from WWTPs to lake sediments. Our work is novel in that we used metagenomic data sets to comprehensively evaluate total gene content and the genetic and taxonomic context of specific genes in environmental samples putatively impacted by WWTP inputs. Based on two different WWTPs with different treatment processes, our findings point to an influence of WWTPs on the presence, abundance, and composition of these factors in the environment.
Enteric Viruses in Surface Waters from Argentina: Molecular and Viable-Virus Detection
Authors: Masachessi G. , Pisano M. B. , Prez V. E. , Martínez L. C. , Michelena J. F. , Martínez-Wassaf M. , Giordano M. O. , Isa M. B. , Pavan J. V. , Welter A. , Nates S. V. , Ré V.
Published: February 2018

Water resources contaminated with wastewater are an important source for the dissemination of enteric viruses with an impact on the health of the population. The aim of the study was to assess the viral contamination of freshwater from a dam in Argentina by using infectious enterovirus detection, viral RNA amplification, and a genetic characterization of five enteric viruses associated with diarrhea and hepatitis. Enterovirus infectivity (iEV) was evaluated by cell culture and direct immunofluorescence. The detection of the viral genome of rotavirus (RV), human astrovirus (HAstV), norovirus (NoV), hepatitis A virus (HAV), and hepatitis E virus (HEV) was performed by reverse transcriptase PCR (RT-PCR). A total of 48 water samples from 4 monitoring points on the body of the dam from January to December 2012 and 66 water samples from 3 tourist beaches on the edge of the dam from October 2013 to October 2015 were collected monthly. During the first period, the overall viral frequency detection was 52.1% for group A RV, 50% for HAstV, 60.4% for NoV, 22.9% for HAV, 2.1% for HEV, and 64.6% for iEV. The overall frequency detection for the second sampling was 18.2% for RV and HAstV, 31.8% for NoV, 7.57% for HEV, and 66.7% for iEV. There was no detection of HAV during this period. The genotypes and genogroups detected through the study correlated with the most common genomic variants associated with human gastrointestinal and hepatitis illnesses. The results obtained could alert the health systems and environmental sanitation to make decisions for viral control and prevention in our environment.

IMPORTANCE
The study shows the impact of anthropic contamination of one of the most important tourist water resources in Argentina. This course of recreational water would be a favorable scenario for infection, as well as a reservoir for the enteric viruses, creating a risk for the population exposed to these waters. The results obtained could alert the health systems and environmental sanitation to make decisions for the control and prevention of viral diseases in this environment.
Staphylococcal Osteomyelitis: Disease Progression, Treatment Challenges, and Future Directions
Authors: Kavanagh Nicola , Ryan Emily J. , Widaa Amro , Sexton Gillian , Fennell Jerome , O'Rourke Sadhbh , Cahill Kevin C. , Kearney Cathal J. , O'Brien Fergal J. , Kerrigan Steven W.
Published: February 2018

Osteomyelitis is an inflammatory bone disease that is caused by an infecting microorganism and leads to progressive bone destruction and loss. The most common causative species are the usually commensal staphylococci, with
Staphylococcus aureus
and
Staphylococcus epidermidis
responsible for the majority of cases. Staphylococcal infections are becoming an increasing global concern, partially due to the resistance mechanisms developed by staphylococci to evade the host immune system and antibiotic treatment. In addition to the ability of staphylococci to withstand treatment, surgical intervention in an effort to remove necrotic and infected bone further exacerbates patient impairment. Despite the advances in current health care, osteomyelitis is now a major clinical challenge, with recurrent and persistent infections occurring in approximately 40% of patients. This review aims to provide information about staphylococcus-induced bone infection, covering the clinical presentation and diagnosis of osteomyelitis, pathophysiology and complications of osteomyelitis, and future avenues that are being explored to treat osteomyelitis.
Virulence of the Melioidosis Pathogen Burkholderia pseudomallei Requires the Oxidoreductase Membrane Protein DsbB
Authors: McMahon Róisín M. , Ireland Philip M. , Sarovich Derek S. , Petit Guillaume , Jenkins Christopher H. , Sarkar-Tyson Mitali , Currie Bart J. , Martin Jennifer L.
Published: February 2018

The naturally antibiotic-resistant bacterium
Burkholderia pseudomallei
is the causative agent of melioidosis, a disease with stubbornly high mortality and a complex, protracted treatment regimen. The worldwide incidence of melioidosis is likely grossly underreported, though it is known to be highly endemic in northern Australia and Southeast Asia. Bacterial disulfide bond (DSB) proteins catalyze the oxidative folding and isomerization of disulfide bonds in substrate proteins. In the present study, we demonstrate that
B. pseudomallei
membrane protein disulfide bond protein B (BpsDsbB) forms a functional redox relay with the previously characterized virulence mediator
B. pseudomallei
disulfide bond protein A (BpsDsbA). Genomic analysis of diverse
B. pseudomallei
clinical isolates demonstrated that
dsbB
is a highly conserved core gene. Critically, we show that DsbB is required for virulence in
B. pseudomallei
. A panel of
B. pseudomallei
dsbB
deletion strains (K96243, 576, MSHR2511, MSHR0305b, and MSHR5858) were phenotypically diverse according to the results of
in vitro
assays that assess hallmarks of virulence. Irrespective of their
in vitro
virulence phenotypes, two deletion strains were attenuated in a BALB/c mouse model of infection. A crystal structure of a DsbB-derived peptide complexed with BpsDsbA provides the first molecular characterization of their interaction. This work contributes to our broader understanding of DSB redox biology and will support the design of antimicrobial drugs active against this important family of bacterial virulence targets.
Reduction of Spermidine Content Resulting from Inactivation of Two Arginine Decarboxylases Increases Biofilm Formation in Synechocystis sp. Strain PCC 6803
Authors: Kera Kota , Nagayama Tatsuya , Nanatani Kei , Saeki-Yamoto Chika , Tominaga Akira , Souma Satoshi , Miura Nozomi , Takeda Kota , Kayamori Syunsuke , Ando Eiji , Higashi Kyohei , Igarashi Kazuei , Uozumi Nobuyuki
Published: February 2018

The phototropic bacterium
Synechocystis
sp. strain PCC 6803 is able to adapt its morphology in order to survive in a wide range of harsh environments. Under conditions of high salinity, planktonic cells formed cell aggregates in culture. Further observations using crystal violet staining, confocal laser scanning microscopy, and field emission-scanning electron microscopy confirmed that these aggregates were
Synechocystis
biofilms. Polyamines have been implicated in playing a role in biofilm formation, and during salt stress the content of spermidine, the major polyamine in
Synechocystis
, was reduced. Two putative arginine decarboxylases, Adc1 and Adc2, in
Synechocystis
were heterologously expressed in
Escherichia coli
and purified. Adc2 had high arginine decarboxylase activity, whereas Adc1 was much less active. Disruption of the
adc
genes in
Synechocystis
resulted in decreased spermidine content and formation of biofilms even under nonstress conditions. Based on the characterization of the
adc
mutants, Adc2 was the major arginine decarboxylase whose activity led to inhibition of biofilm formation, and Adc1 contributed only minimally to the process of polyamine synthesis. Taken together, in
Synechocystis
the shift from planktonic lifestyle to biofilm formation was correlated with a decrease in intracellular polyamine content, which is the inverse relationship of what was previously reported in heterotroph bacteria.

IMPORTANCE
There are many reports concerning biofilm formation in heterotrophic bacteria. In contrast, studies on biofilm formation in cyanobacteria are scarce. Here, we report on the induction of biofilm formation by salt stress in the model phototrophic bacterium
Synechocystis
sp. strain PCC 6803. Two arginine decarboxylases (Adc1 and Adc2) possess function in the polyamine synthesis pathway. Inactivation of the
adc1
and
adc2
genes leads to biofilm formation even in the absence of salt. The shift from planktonic culture to biofilm formation is regulated by a decrease in spermidine content in
Synechocystis
. This negative correlation between biofilm formation and polyamine content, which is the opposite of the relationship reported in other bacteria, is important not only in autotrophic but also in heterotrophic bacteria.
Identification of Streptococcus gallolyticus subsp. gallolyticus (Biotype I) Competence-Stimulating Peptide Pheromone
Authors: Harrington Anthony , Tal-Gan Yftah
Published: February 2018

Streptococcus gallolyticus
subsp.
gallolyticus
, a member of the group D streptococci, is normally found in the bovine rumen and human gut. It is an opportunistic pathogen that was recently determined to be a bacterial driver of colorectal cancer, in addition to causing other diseases, such as infective endocarditis, bacteremia, neonatal meningitis, and septicemia. As an emerging pathogen, not much is known about this bacterium, its virulence mechanisms, or its virulence regulatory pathways. Previous studies suggest that
S. gallolyticus
subsp.
gallolyticus
uses a ComRS pathway, one of many
Streptococcus
quorum-sensing circuitries, for competence. However, thus far, the ubiquitous ComABCDE pathway has not been studied, nor has its regulatory role in
S. gallolyticus
subsp.
gallolyticus
. We therefore sought to study the
S. gallolyticus
subsp.
gallolyticus
ComABCDE quorum-sensing pathway and have identified its peptide pheromone, which is termed the competence-stimulating peptide (CSP). We further determined that this peptide regulates the production of bacteriocin-like inhibitory substances (BLISs), a phenotype that has been linked with the ComABCDE pathway in both
Streptococcus pneumoniae
and
Streptococcus mutans
. Our data show that
S. gallolyticus
subsp.
gallolyticus
TX20005 produces a 21-mer CSP signal, which differs from CSP signals of other
Streptococcus
species in that its active form begins three residues after the double-glycine leader signal of the ComC precursor peptide. Additionally, our data suggest that this peptide might not be related to competence induction, as opposed to CSP signaling peptides in other
Streptococcus
species. This study provides the first evidence that
S. gallolyticus
subsp.
gallolyticus
utilizes quorum sensing to eliminate competitors, presenting a potential pathway to target this emerging human pathogen.

IMPORTANCE
Streptococcus gallolyticus
subsp.
gallolyticus
is an emerging human pathogen known as a causative agent of infective endocarditis, and recently, of colorectal cancer. In this work, we revealed a functional quorum-sensing circuitry in
S. gallolyticus
subsp.
gallolyticus
, including the identification of the central signaling peptide pheromone, competence-stimulating peptide (CSP), and the regulatory role of this circuitry in the production of bacteriocin-like inhibitory substances (BLISs). This work uncovered a mechanism by which this bacterium outcompetes other bacterial species and thus provides a potential tool to study this opportunistic pathogen.
Expression of Pyridoxal 5′-Phosphate-Independent Racemases Can Reduce 2-Aminoacrylate Stress in Salmonella enterica
Authors: Hodge-Hanson Kelsey M. , Zoino Allison , Downs Diana M.
Published: February 2018

The RidA protein (PF01042) from
Salmonella enterica
is a deaminase that quenches 2-aminoacrylate (2AA) and other reactive metabolites. In the absence of RidA, 2AA accumulates, damages cellular enzymes, and compromises the metabolic network.
In vitro
, RidA homologs from all domains of life deaminate 2AA, and RidA proteins from plants, bacteria, yeast, and humans complement the mutant phenotype of a
ridA
mutant strain of
S. enterica
. In the present study, a methanogenic archaeon,
Methanococcus maripaludis
S2, was used to probe alternative mechanisms to restore metabolic balance.
M. maripaludis
MMP0739, which is annotated as an aspartate/glutamate racemase, complemented a
ridA
mutant strain and reduced the intracellular 2AA burden. The aspartate/glutamate racemase YgeA from
Escherichia coli
or
S. enterica
, when provided in
trans
, similarly restored wild-type growth to a
ridA
mutant. These results uncovered a new mechanism to ameliorate metabolic stress, and they suggest that direct quenching by RidA is not the only strategy to quench 2AA.

IMPORTANCE
2-Aminoacrylate is an endogenously generated reactive metabolite that can damage cellular enzymes if not directly quenched by the conserved deaminase RidA. This study used an archaeon to identify a RidA-independent mechanism to prevent metabolic stress caused by 2AA. The data suggest that a gene product annotated as an aspartate/glutamate racemase (MMP0739) produces a metabolite that can quench 2AA, expanding our understanding of strategies available to quench reactive metabolites.
Lactic Acid Downregulates Viral MicroRNA To Promote Epstein-Barr Virus-Immortalized B Lymphoblastic Cell Adhesion and Growth
Authors: Mo Xiaohui , Wei Fang , Tong Yin , Ding Ling , Zhu Qing , Du Shujuan , Tan Fei , Zhu Caixia , Wang Yuyan , Yu Qian , Liu Yeqiang , Robertson Erle S. , Yuan Zhenghong , Cai Qiliang
Published: February 2018

High plasma lactate is associated with poor prognosis of many malignancies, but its role in virally mediated cancer progression and underlying molecular mechanisms are unclear. Epstein-Barr virus (EBV), the first human oncogenic virus, causes several cancers, including B-cell lymphoma. Here, we report that lactate dehydrogenase A (LDH-A) expression and lactate production are elevated in EBV-immortalized B lymphoblastic cells, and lactic acid (LA; acidic lactate) at low concentration triggers EBV-infected B-cell adhesion, morphological changes, and proliferation
in vitro
and
in vivo
. Moreover, LA-induced responses of EBV-infected B cells uniquely occurs in viral latency type III, and it is dramatically associated with the inhibition of global viral microRNAs, particularly the miR-BHRF1 cluster, and the high expression of
SMAD3
,
JUN
, and
COL1A
genes. The introduction of miR-BHRF1-1 blocks the LA-induced effects of EBV-infected B cells. Thus, this may be a novel mechanism to explain EBV-immortalized B lymphoblastic cell malignancy in an LA microenvironment.

IMPORTANCE
The tumor microenvironment is complicated, and lactate, which is created by cell metabolism, contributes to an acidic microenvironment that facilitates cancer progression. However, how LA operates in virus-associated cancers is unclear. Thus, we studied how EBV (the first tumor virus identified in humans; it is associated with many cancers) upregulates the expression of LDH-A and lactate production in B lymphoma cells. Elevated LA induces adhesion and the growth of EBV-infected B cells by inhibiting viral microRNA transcription. Thus, we offer a novel understanding of how EBV utilizes an acidic microenvironment to promote cancer development.
Health professionals’ and coroners’ views on less invasive perinatal and paediatric autopsy: a qualitative study
Authors: Lewis Celine , Hill Melissa , Arthurs Owen J , Hutchinson John C , Chitty Lyn S , Sebire Neil
Published: February 2018

Objective

To assess health professionals’ and coroners’ attitudes towards non-minimally and minimally invasive autopsy in the perinatal and paediatric setting.

Methods

A qualitative study using semistructured interviews. Data were analysed thematically.

Results

Twenty-five health professionals (including perinatal/paediatric pathologists and anatomical pathology technologists, obstetricians, fetal medicine consultants and bereavement midwives, intensive care consultants and family liaison nurses, a consultant neonatologist and a paediatric radiologist) and four coroners participated. Participants viewed less invasive methods of autopsy as a positive development in prenatal and paediatric care that could increase autopsy rates. Several procedural and psychological benefits were highlighted including improved diagnostic accuracy in some circumstances, potential for faster turnaround times, parental familiarity with imaging and laparoscopic approaches, and benefits to parents and faith groups who object to invasive approaches. Concerns around the limitations of the technology such not reaching the same levels of certainty as full autopsy, unsuitability of imaging in certain circumstances, the potential for missing a diagnosis (or misdiagnosis) and de-skilling the workforce were identified. Finally, a number of implementation issues were raised including skills and training requirements for pathologists and radiologists, access to scanning equipment, required computational infrastructure, need for a multidisciplinary approach to interpret results, cost implications, equity of access and acceptance from health professionals and hospital managers.

Conclusion

Health professionals and coroners viewed less invasive autopsy as a positive development in perinatal and paediatric care. However, to inform implementation a detailed health economic analysis and further exploration of parental views, particularly in different religious groups, are required.
Isolated intraventricular hemorrhage secondary to dural arteriovenous fistula
Authors: Amuluru Krishna , Al-Mufti Fawaz , Romero Charles
Published: February 2018

Isolated intraventricular hemorrhage due to dural arteriovenous fistula (dAVF) is extremely rare and has been reported only a few times in the literature. The pathophysiological cause of isolated intraventricular hemorrhage in these cases was hypothetically attributed to retrograde venous flow into subependymal vessels, although none of these cases demonstrated radiographic evidence of such reflux. We present the first case of a dAVF with radiographic evidence of severe cortical venous reflux into the subependymal venous network causing isolated intraventricular hemorrhage, thus lending proof for the underlying pathophysiology. Furthermore, ours is the first case of dAVF with isolated intraventricular hemorrhage that was successfully treated using multimodality transvenous and transarterial embolization techniques. In cases of high-grade dAVF, multimodality treatment may offer the greatest chance for success, and should be strongly considered for management.
Yellow (577 nm) micropulse laser versus half-dose verteporfin photodynamic therapy in eyes with chronic central serous chorioretinopathy: results of the Pan-American Collaborative Retina Study (PACORES) Group
Authors: Roca Jose A , Wu Lihteh , Fromow-Guerra Jans , Rodríguez Francisco J , Berrocal Maria H , Rojas Sergio , Lima Luiz H , Gallego-Pinazo Roberto , Chhablani Jay , Arevalo J Fernando , Lozano-Rechy David , Serrano Martin
Published: February 2018

Purpose

To compare the functional and anatomical outcomes of eyes with chronic central serous chorioretinopathy treated with yellow micropulse (MP) laser versus half-dose verteporfin photodynamic therapy (PDT).

Methods

This is a multicentre, retrospective comparative study of 92 eyes treated with yellow MP laser (duty cycle of 5%, zero spacing between spots, spot size varied from 100 to 200 µm, power varied from 320 to 660 mW, and the pulse burst duration was 200 ms) and 67 eyes treated with PDT (half-dose verteporfin (3 mg/m2) infused over 10 min), followed by laser activation for 83 s. Spot sizes varied from 400 to 2000 µm.

Results

In the MP group, at 12 months of follow-up, the mean best corrected visual acuity (BCVA) improved from the logarithm of the minimum angle of resolution (logMAR) of 0.41±0.27 at baseline to 0.21±0.26 (P<0.0001), 48.9% (45/92) of eyes had an improvement of ≥3 lines of BCVA from baseline, 48.9% (45/92) of eyes remained within 2 lines of baseline BCVA, and only 2.2% (2/92) of eyes lost ≥3 lines of BCVA from baseline. In the PDT group, at 12 months of follow-up, the mean BCVA changed from logMAR of 0.50±0.34 at baseline to 0.47±0.34 (P=0.89), 19% (13/67) of eyes had an improvement of ≥3 lines of BCVA from baseline, 73% (49/67) of eyes remained within 2 lines of baseline BCVA, and 7% (5/67) of eyes lost ≥3 lines of BCVA from baseline. There were no adverse events attributable to the yellow MP laser treatment. One eye in the PDT group developed choroidal neovascularisation, which was treated with three intravitreal bevacizumab injections.

Conclusions

Both PDT and MP are effective in restoring the macular anatomy. In places where PDT is not available, yellow MP laser may be an adequate treatment alternative.
Primary photodynamic therapy with verteporfin for pigmented posterior pole cT1a choroidal melanoma: a 3-year retrospective analysis
Authors: Fabian Ido Didi , Stacey Andrew W , Harby Lamis Al , Arora Amit K , Sagoo Mandeep S , Cohen Victoria M L
Published: February 2018

Aims

To investigate the outcomes of primary photodynamic therapy (PDT) for pigmented posterior pole cT1a choroidal melanoma.

Methods

Retrospective interventional consecutive case series of 26 patients (26 eyes) with pigmented posterior pole cT1a choroidal melanoma, who were treated with 3 sessions of PDT and followed-up thereafter.

Results

Included were 11 males and 15 females that presented at a median age of 66 years (mean: 64) with transformed naevi (n=11) or suspicious lesions (n=15) with ≥3 risk factors for growth, with lipofuscin in all. In all cases, diagnosis was clinically based (no tissue biopsy). Tumour control was achieved in 16 (62%) patients in a median follow-up time of 29 months (mean: 27). Ten patients failed treatment by form of radial expansion, diagnosed in a median time of 13 months (mean: 12) from last treatment. By Kaplan-Meier analysis, success rate after 1, 2 and 3 years was 85%, 59% and 51%, respectively. On statistical analysis, number of suspicious features was found to be the only risk factor predicting failure (P=0.046). One patient developed macula-sparing branch retinal artery occlusion after treatment. Following PDT, subretinal fluid resolved in all cases and visual acuity significantly improved in all treatment-success cases (P=0.043). There were no cases of metastatic spread.

Conclusion

Primary PDT resulted in tumour regression of small, pigmented choroidal melanoma in 62% after a mean of 27 months. Treatment was more effective in tumours with three or less risk factors for growth, and resulted with fluid elimination and significant improvement in vision in treatment-success cases.
Evaluation of patient-reported outcome protocol content and reporting in UK cancer clinical trials: the EPiC study qualitative protocol
Authors: Retzer Ameeta , Keeley Thomas , Ahmed Khaled , Armes Jo , Brown Julia M , Calman Lynn , Copland Chris , Efficace Fabio , Gavin Anna , Glaser Adam , Greenfield Diana M , Lanceley Anne , Taylor Rachel M , Velikova Galina , Brundage Michael , Mercieca-Bebber Rebecca , King Madeleine T , Calvert Melanie , Kyte Derek
Published: February 2018

Introduction

Patient-reported outcomes (PROs) are increasingly included within cancer clinical trials. If appropriately collected, analysed and transparently reported, these data might provide invaluable evidence to inform patient care. However, there is mounting indication that the design and reporting of PRO data in cancer trials may be suboptimal. This programme of research will establish via three interlinked studies whether these findings are applicable to UK cancer trials, and if so, how to best enhance the way PROs are assessed, managed and reported in clinical trials. This study will explore with key stakeholders factors that influence optimal PRO protocol content, implementation and reporting and make recommendations for training and guidance.

Methods and analysis

Semistructured interviews will be conducted with members of key stakeholder groups. The purposive sample of up to 48 participants will include: (1) trial chief investigators, trial management group members, statisticians and research nurses of cancer trials including primary or secondary PRO recruited via the National Cancer Research Institute (NCRI) Clinical Studies Group and Consumer Liaison Group and the UK Clinical Research Collaboration Registered UK Clinical Trial Unit Network; (2) NCRI Consumer Liaison Group members; (3) international experts in PRO oncology trial design; and (4) journal editors and funding bodies. Data will be analysed using directed thematic analysis employing a coding frame and modified as analysis progresses. Formal triangulation of coding and member checking will be employed to enhance credibility.

Ethics and dissemination

This study was approved by the University of Birmingham Ethics Committee (Ref: ERN_17–0085). Findings will be disseminated via conference presentations, peer-reviewed journals, patient groups and social media (@CPROR_UoB;http://www.birmingham.ac.uk/cpror).

PROSPERO registration number

CRD42016036533.
To what extent do hospitalised patients receive appropriate CT and MRI scans? Results of a cross-sectional study in Southern Italy
Authors: Bianco Aida , Zucco Rossella , Lotito Francesca , Pavia Maria
Published: February 2018

Objectives

The aim of this study was to assess the frequency of appropriateness of inpatient CT and MRI scans performed in Southern Italy.

Methods

The study was carried out by retrospectively reviewing medical records of adult patients admitted between 1 January and 31 December 2012 in two hospitals. The evaluation of appropriateness was performed according to the American College of Radiology Appropriateness Criteria, which assigns a score between 1 and 9.

Results

Eight hundred and fifty-three medical records were reviewed. Six hundred and thirty-nine patients received CT examinations and 256 received MRI examinations. Four hundred and ninety-six (77.6%) of the patient population had appropriate CT and 202 (78.9%) received appropriate MRI examinations. The appropriateness was associated with: a confirmation of the diagnostic hypothesis, only one examination performed during hospital stay, the anatomical scan region, with musculoskeletal system being the least appropriate anatomical scan region. Moreover, for CT examinations, appropriateness was also associated with no use of contrast agent.

Conclusions

Our findings highlight the need to reduce inappropriate use of CT and MRI. The study showed that the tool used is reliable to measure the extent of appropriateness of diagnostic imaging for inpatient examinations.
Factors associated with health literacy in multimorbid patients in primary care: a cross-sectional study in Switzerland
Authors: N’Goran Alexandra A , Pasquier Jérôme , Deruaz-Luyet Anouk , Burnand Bernard , Haller Dagmar M , Neuner-Jehle Stefan , Zeller Andreas , Streit Sven , Herzig Lilli , Bodenmann Patrick
Published: February 2018

Objective

To identify factors associated with health literacy in multimorbid patients.

Design

A nationwide cross-sectional study in Switzerland. Univariate and multivariate linear regressions were calculated to identify variables associated with health literacy. A multiple imputation approach was used to deal with missing values.

Participants

Multimorbid patients recruited in primary care settings (n=888), above 18 years old and suffering from at least 3 of 75 chronic conditions on a predefined list based on the International Classification of Primary Care 2.

Main measures

Health literacy was assessed using the European Health Literacy Survey project questionnaire (HLS-EU 6). This comprises six items scored from 1 to 4 (very difficult=1, fairly difficult=2, fairly easy=3, very easy=4), and the total health literacy score is computed as their mean. As we wished to understand the determinants associated with lower health literacy, the HLS-EU 6 score was the only dependent variable; all other covariates were considered independent.

Results

The mean health literacy score (SD) was 2.9 (0.5). Multivariate analyses found significant associations between low health literacy scores and treatment burden scores (β=−0.004, 95% CI −0.006 to 0.002); marital status, predominantly the divorced group (β=0.136, 95% CI 0.012 to 0.260); dimensions of the EuroQuol 5 Dimension 3 Level (EQ5D3L) quality of life assessment, that is, for moderate problems with mobility (β=−0.086, 95% CI −0.157 to 0.016); and with moderate problems (β=−0.129, 95% CI −0.198 to 0.060) and severe problems with anxiety/depression (β=−0.343, 95% CI −0.500 to 0.186).

Conclusions

Multimorbid patients with a high treatment burden, altered quality of life by problems with mobility, anxiety or depression, often also have low levels of health literacy. Primary care practitioners should therefore pay particular attention to these patients in their daily practice.
Assessing the nutrient intake of a low-carbohydrate, high-fat (LCHF) diet: a hypothetical case study design
Authors: Zinn Caryn , Rush Amy , Johnson Rebecca
Published: February 2018

Objective

The low-carbohydrate, high-fat (LCHF) diet is becoming increasingly employed in clinical dietetic practice as a means to manage many health-related conditions. Yet, it continues to remain contentious in nutrition circles due to a belief that the diet is devoid of nutrients and concern around its saturated fat content. This work aimed to assess the micronutrient intake of the LCHF diet under two conditions of saturated fat thresholds.

Design

In this descriptive study, two LCHF meal plans were designed for two hypothetical cases representing the average Australian male and female weight-stable adult. National documented heights, a body mass index of 22.5 to establish weight and a 1.6 activity factor were used to estimate total energy intake using the Schofield equation. Carbohydrate was limited to <130 g, protein was set at 15%–25% of total energy and fat supplied the remaining calories. One version of the diet aligned with the national saturated fat guideline threshold of <10% of total energy and the other included saturated fat ad libitum.

Primary outcomes

The primary outcomes included all micronutrients, which were assessed using FoodWorks dietary analysis software against national Australian/New Zealand nutrient reference value (NRV) thresholds.

Results

All of the meal plans exceeded the minimum NRV thresholds, apart from iron in the female meal plans, which achieved 86%–98% of the threshold. Saturated fat intake was logistically unable to be reduced below the 10% threshold for the male plan but exceeded the threshold by 2 g (0.6%).

Conclusion

Despite macronutrient proportions not aligning with current national dietary guidelines, a well-planned LCHF meal plan can be considered micronutrient replete. This is an important finding for health professionals, consumers and critics of LCHF nutrition, as it dispels the myth that these diets are suboptimal in their micronutrient supply. As with any diet, for optimal nutrient achievement, meals need to be well formulated.
Challenges of diagnosis and management of giant cell arteritis in general practice: a multimethods study
Authors: Helliwell Toby , Muller Sara , Hider Samantha L , Prior James A , Richardson Jane C , Mallen Christian D
Published: February 2018

Background

In the UK, general practitioners (GPs) are usually the first medical contact for patients with suspected giant cell arteritis (GCA). While rare, it is critical not to miss, as delayed treatment can lead to significant complications including permanent visual loss. To date, little is known about the approach and challenges to diagnosis and management of GCA by GPs.

Objective

To investigate the diagnosis and management of patients with suspected GCA in UK general practice.

Design and participants

A multimethods approach was taken, comprising a postal survey of 5000 randomly selected UK GPs and semistructured telephone interviews of 24 GPs from across the UK.

Setting

UK general practice.

Results

1249 questionnaires were returned. 879 responders (70%) indicated that they had diagnosed and managed a patient with GCA. A variety of clinical features were used to identify GCA. 21.9% suggested that they would exclude GCA as a diagnosis if headache was absent and around one-third do not routinely initiate glucocorticoid treatment prior to referral. Significant regional variations in referral pathways were reported. Thematic analysis of interview transcripts highlighted fears relating to a missed diagnosis of GCA and the non-specific nature of early GCA presentation. Accessing specialist care was highlighted as challenging by many GPs and that a national standard fast-track pathway is lacking to support this patient group. Additionally there were significant concerns regarding potential adverse effects relating to long-term treatment with glucocorticoids.

Conclusion

GPs appear to over-rely on headache to identify GCA and marked geographical differences in management, with conflicting referral pathways and difficulties in accessing appropriate services exist in the UK. A national standard for fast-tracking patients with suspected GCA to relevant specialists would be beneficial to improve care and outcomes for patients with GCA.
‘Care Under Pressure’: a realist review of interventions to tackle doctors’ mental ill-health and its impacts on the clinical workforce and patient care
Authors: Carrieri Daniele , Briscoe Simon , Jackson Mark , Mattick Karen , Papoutsi Chrysanthi , Pearson Mark , Wong Geoffrey
Published: February 2018

Introduction

Mental ill-health is prevalent across all groups of health professionals and this is of great concern in many countries. In the UK, the mental health of the National Health Service (NHS) workforce is a major healthcare issue, leading to presenteeism, absenteeism and loss of staff from the workforce. Most interventions targeting doctors aim to increase their ‘productivity’ and ‘resilience’, placing responsibility for good mental health with doctors themselves and neglecting the organisational and structural contexts that may have a detrimental effect on doctors’ well-being. There is a need for approaches that are sensitive to the contextual complexities of mental ill-health in doctors, and that do not treat doctors as a uniform body, but allow distinctions to account for particular characteristics, such as specialty, career stage and different working environments.

Methods and analysis

Our project aims to understand how, why and in what contexts support interventions can be designed to minimise the incidence of doctors’ mental ill-health. We will conduct a realist review—a form of theory-driven interpretative systematic review—of interventions, drawing on diverse literature sources. The review will iteratively progress through five steps: (1) locate existing theories; (2) search for evidence; (3) select articles; (4) extract and organise data and (5) synthesise evidence and draw conclusions. The analysis will summarise how, why and in what circumstances doctors’ mental ill-health is likely to develop and what can remediate the situation. Throughout the project, we will also engage iteratively with diverse stakeholders in order to produce actionable theory.

Ethics and dissemination

Ethical approval is not required for our review. Our dissemination strategy will be participatory. Tailored outputs will be targeted to: policy makers; NHS employers and healthcare leaders; team leaders; support organisations; doctors experiencing mental ill-health, their families and colleagues.

PROSPERO registration number

CRD42017069870.
Using a network organisational architecture to support the development of Learning Healthcare Systems
Authors: Britto Maria T , Fuller Sandra C , Kaplan Heather C , Kotagal Uma , Lannon Carole , Margolis Peter A , Muething Stephen E , Schoettker Pamela J , Seid Michael
Published: February 2018

The US National Academy of Sciences has called for the development of a Learning Healthcare System in which patients and clinicians work together to choose care, based on best evidence, and to drive discovery as a natural outgrowth of every clinical encounter to ensure innovation, quality and value at the point of care. However, the vision of a Learning Healthcare System has remained largely aspirational. Over the last 13 years, researchers, clinicians and families, with support from our paediatric medical centre, have designed, developed and implemented a network organisational model to achieve the Learning Healthcare System vision. The network framework aligns participants around a common goal of improving health outcomes, transparency of outcome measures and a flexible and adaptive collaborative learning system. Team collaboration is promoted by using standardised processes, protocols and policies, including communication policies, data sharing, privacy protection and regulatory compliance. Learning methods include collaborative quality improvement using a modified Breakthrough Series approach and statistical process control methods. Participants observe their own results and learn from the experience of others. A common repository (a ‘commons’) is used to share resources that are created by participants. Standardised technology approaches reduce the burden of data entry, facilitate care and result in data useful for research and learning. We describe how this organisational framework has been replicated in four conditions, resulting in substantial improvements in outcomes, at scale across a variety of conditions.
New decision formulas for predicting endotracheal tube depth in children: analysis of neck CT images
Authors: Lee Se Uk , Jung Jae Yun , Kim Do Kyun , Kwak Young Ho , Kwon Hyuksool , Cho Jun Hwi , Park Joong Wan , Choi Yoo Jin
Published: February 2018

Introduction

The purpose of this study was to construct a prediction model for endotracheal tube depth using neck CT images.

Methods

A retrospective image review was conducted that included patients who had undergone neck CT. Using sagittal neck CT images, we calculated the length between upper incisor and mid-trachea and then derived the model via regression analysis. The model was validated externally using chest radiographs of patients who had undergone endotracheal intubation. We compared performance of our model with that of other methods (Broselow tape and APLS formula) via Bland-Altman analysis and the percentage of estimations within 10% of the measured values.

Results

A total of 1111 children were included in this study. The tube depth obtained from CT images was linearly related to body weight (tube depth (cm)=5.5+0.5×body wt (kg)) in children younger than 1 year and to height (tube depth (cm)=3+0.1×height (cm)) in children older than 1 year. External validation demonstrated that our new model showed better agreement with the desired tube depth than Broselow tape and APLS formula. The mean differences in children younger than 1 year were 0.61 cm and −1.24 cm for our formula and Broselow tape, respectively. The mean differences in children older than 1 year were −0.43 cm, −1.98 and −1.64 cm for our formula, Broselow tape and APLS formula, respectively. The percentages of estimates within 10% of the measured values were 52.7% and 35.8% for our formula and Broselow tape in children younger than 1 year, respectively, and 54.3%, 33.8% and 37.2% for our formula, Broselow tape and APLS formula in children older than 1 year, respectively (P<0.01).

Conclusion

Our new formula is useful and more accurate than the currently available methods.
Exposure to traffic-related air pollution and acute bronchitis in children: season and age as modifiers
Authors: Bai Lijun , Su Xi , Zhao Desheng , Zhang Yanwu , Cheng Qiang , Zhang Heng , Wang Shusi , Xie Mingyu , Su Hong
Published: February 2018

Background

Acute bronchitis (AB) is one of the principal causes of childhood morbidity. Increasing number of studies has shown that air pollution is an important environmental contributor of respiratory disease. However, evidence so far is scarce regarding the effects of air pollution on childhood AB, and it also remains unclear how the risk of AB will change by season and age.

Methods

Data on hospital visits for AB in children, air pollution and meteorological factors from 1 January 2015 to 31 December 2016 were collected in Hefei, China. Time-series analysis was applied to assess the short-term effects of traffic-related air pollution on childhood AB outpatient visits. A Poisson generalised linear regression model combined with a distributed lag non-linear model was used to estimate the relationships, controlling for long-term trends, seasonal patterns, meteorological factors and other possible confounders.

Results

We found that an IQR increase in concentrations of nitrogen dioxide, particulate matter <2.5 µm and carbon monoxide significantly increased the daily hospital visits for childhood AB with 4-day cumulative effect estimates (relative risks: 1.03, 95% CI 1.01 to 1.05; 1.09, 95% CI 1.07 to 1.11; 1.07, 95% CI 1.05 to 1.09). Notably, the risk estimates during the cold season are pronounced; however, no significant association was observed during the warm season. Interestingly, children aged 6–14 years were more vulnerable to air pollutants than children aged less than 1 year and within 1–5 years. However, no gender difference was observed.

Conclusion

A significant association of traffic-related air pollution and increased department visits for childhood AB was observed, notably in school-age children and during the cold season.