bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative study of efficacy, rapidity of detection, and cost‐effectiveness of potassium hydroxide, calcofluor white, and Chicago sky blue stains in the diagnosis of dermatophytoses
Authors: Prakash R. , Prashanth Hosakere Veerappa , Ragunatha Shivanna , Kapoor Meenakshi , Anitha T. K. , Krishnamurthy Veena
Published: February 2016

Background

The diagnosis of superficial mycosis such as dermatophytosis is often done clinically. However, in difficult cases, a rapid test with high sensitivity and specificity helps in the immediate confirmation and administration of treatment.

Methods

The efficacy, rapidity of detection, and cost‐effectiveness of KOH preparation, calcofluor white (CW) stain, and Chicago sky blue (CSB) stain in the identification of fungal elements were assessed in patients with dermatophytoses attending the dermatology clinic of a tertiary care hospital. All three tests were performed on each sample collected from 73 patients according to standard procedure. The slides were examined after 5 and 30 minutes in × 10 and × 40 magnifications. The sensitivity and specificity of CW and CSB at 5 and 30 minutes were calculated using KOH preparation as the standard test.

Results

CSB stain showed highest positivity (94.5%) within 5 minutes when compared to KOH (75.3%) and CW (83.5%). After 30 minutes, positivity increased in KOH (84.9%) and CW stains (89%), but it remained the same in CSB stain. Both CW and CSB stains when compared to 10% KOH are equally sensitive (100%), but CW was more specific (72.7%), particularly at 30 minutes. When cost of performing tests on 100 specimens is considered, KOH, CW, and CSB stains cost Rs 5, 100, and 15, respectively.

Conclusion

CSB stain is a better stain for rapid diagnosis of dermatophytoses because of ease of performance, rapidity of detection, better appreciation of morphology of fungal elements, and cost effectiveness.
Characterization of a new HLA‐A allele, HLA‐A*02:07:08, by cloning and sequencing
Authors: Wang W. Y. , Zhang W. , Li L. X. , Zhu F. M. , Tian W.
Published: February 2016

In this report, we present a novel HLA‐A*02:07 allele, HLA‐A*02:07:08. HLA‐A*02:07:08 was identified in an individual of Han ethnicity in Hunan province, southern China. Following polymerase chain reaction‐sequence‐based typing (PCR‐SBT), this new allele was further confirmed by cloning and sequencing. HLA‐A*02:07:08 differs from HLA‐A*02:07:01 by a single synonymous C to T substitution at nucleotide position 131 in exon 3.
Structural Transitions Induced by Ion Irradiation in V2AlC and Cr2AlC
Authors: Wang Chenxu , Yang Tengfei , Xiao Jingren , Liu Shaoshuai , Xue Jianming , Huang Qing , Zhang Jie , Wang Jingyang , Wang Yugang
Published: February 2016

Nanolayered structural metallic ceramics, MAX phases, possess unique and highly attractive properties, including excellent radiation tolerance for some of them, whereas little is known about the detailed process of irradiation‐induced structural transitions. In this study, the microstructural transformations and the stabilities of V2AlC and Cr2AlC induced by 1 MeV Au+ ions irradiation over a wide range of fluences were investigated by grazing incidence X‐ray diffraction (GIXRD) and transmission electron microscopy (TEM). GIXRD analyses show different processes of phase transitions and amorphization tolerance under irradiation between these two MAX phases, which are consistent with the selected area electron diffraction (SAED) results and the high‐resolution observations. TEM observations reveal that the nanolamellar structures are disturbed and respective phase transitions occur at relatively low fluences, with the formation of stacking faults. As the fluence increases, Cr2AlC becomes completely amorphous, while V2AlC are gradually transformed into face‐centered cubic (fcc) structure from the original hexagonal close‐packed (hcp) structure without amorphization, indicating that V2AlC is more tolerant of irradiation than Cr2AlC. Based on the phase contrast images and the electron‐diffraction pattern (EDP) simulation of the microstructures, mechanisms of the phase transitions of V2AlC and Cr2AlC are proposed and the difference of the irradiation tolerance between them is discussed.
Upconversion Luminescence and Energy‐Transfer Mechanism of NaGd(MoO4)2: Yb3+/Er3+ Microcrystals
Authors: Li Anming , Xu Dekang , Zhang Yueli , Lin Hao , Yang Shenghong , Chen Zhenqiang , Shao Yuanzhi
Published: February 2016

Uniform and well‐crystallized NaGd(MoO4)2: Yb3+/Er3+ microcrystals with tetragonal plate morphology were synthesized by a facile hydrothermal method. The structure and phase purity of the samples were identified by powder XRD analysis. The steady‐state and transient luminescence spectra were measured and analyzed. Under 980 nm excitation, intense green luminescence at 531 and 553 nm, and red luminescence at 657 and 670 nm were observed. The optimum doping concentrations for Yb3+ and Er3+ are determined to be 20% and 1% in NaGd(MoO4)2 tetragonal plate microcrystals. With increasing Yb3+ doping concentrations, the total integral emission intensities increase first and then decrease. The red/green intensity ratio of NaGd(MoO4)2: Yb3+/Er3+ microcrystals increases from 0.4 to 1.0 with the increase in Yb3+ concentrations. Based on the energy level diagram, the energy‐transfer mechanisms are investigated in detail according to the double logarithmic plot of upconversion intensities versus pump powers. The energy‐transfer mechanisms for green and red upconversion luminescence are ascribed to two‐photon processes at lower Yb3+ concentrations, and involve high‐Yb3+‐induced one‐photon processes at higher Yb3+ concentrations. For the red upconversion luminescence, energy back‐transfer process, that is, 4S3/2 (Er3+) + 2F7/2 (Yb3+) → 4I13/2 (Er3+) + 2F5/2 (Yb3+), is dominant at higher Yb3+ concentrations. Theoretical model of the energy‐transfer mechanisms based on rate equations is established, which agrees well with the experimental results.
Core–Shell Structure and Dielectric Properties of Ba0.991Bi0.006TiO3@Nb2O5–Co3O4 Ceramics
Authors: Liu Yu , Cui Bin , Wang Yan , Ma Rong , Shangguan Mengqian , Zhao Xiaotong , Wang Shuhao , Li Qianyu , Wang Yaoyu
Published: February 2016

To meet the needs of future multilayer ceramic capacitors (MLCCs), thinner dielectric layers are necessary. To achieve this goal, the grain size and uniformity of the particles must be effectively controlled. In this study, we confirmed a core–shell particle structure by means of X‐ray diffraction, scanning electron microscopy, and energy‐dispersive spectroscopy. The dielectric properties of the ceramics were measured using an LCR meter. We found Ba0.991Bi0.006TiO3 particles form a core that was coated with a homogeneous Nb2O5–Co3O4 layer (~9 nm). The relationship between core–shell structure and εr‐T curves of the Ba0.991Bi0.006TiO3@Nb2O5–Co3O4 ceramics by different sintering temperature has been investigated. Dense, fine‐grained Ba0.991Bi0.006TiO@Nb2O5–Co3O4 ceramics were obtained by sintering at 1160°C. The ceramics met the X8R requirements, with a maximum dielectric constant of 2795, and a low dielectric loss at room temperature of 0.89%.
Densification of Yttria Transparent Ceramics: The Utilization of Activated Sintering
Authors: Wang Jun , Zhang Jian , Ning Kaijie , Luo Dewei , Yang Hao , Yin Danlei , Tang Dingyuan , Kong Ling Bing
Published: February 2016

Highly transparent 0.5 at.% Tm:Y2O3 ceramics were prepared by using solid‐state reaction combined with vacuum sintering method, with ZrO2 and Al2O3 as sintering aids. Doping amount of ZrO2 was fixed at 1 at.%, while the effect of Al2O3 on densification, microstructure evolution, and transmittance of the Y2O3 ceramics was carefully studied. It was found that the addition of Al2O3 was very effective in improving densification of Y2O3, due to the formation of an Al‐rich eutectic phase Y4Al2O9 (YAM) during the sintering process. As the content of Al2O3 was increased from 0 to 81.8 wt ppm, porosity of the ceramics was decreased and transmittance was increased. However, when the content of Al2O3 was increased to 137 wt ppm, a secondary phase began to segregate at grain junctions. Further increase in the amount of Al2O3 led to an increase in both amount and size of the secondary phase. At the optimized content of Al2O3 with 81.8 wt ppm, the Tm:Y2O3 ceramics sintered at 1860°C for 13 h exhibited an in‐line transmittance of 83.0% at 2000 nm and 76.5% at 600 nm. It is expected that this finding can be readily applied to other transparent ceramics.
Naringenin targets ERK2 and suppresses UVB‐induced photoaging
Authors: Jung Sung Keun , Ha Su Jeong , Jung Chang Hwa , Kim Yun Tai , Lee Hoo‐Keun , Kim Myoung Ok , Lee Mee‐Hyun , Mottamal Madhusoodanan , Bode Ann M. , Lee Ki Won , Dong Zigang
Published: February 2016

A number of natural phytochemicals have anti‐photoaging properties that appear to be mediated through the inhibition of matrix metalloproteinase‐1 (MMP‐1) expression, but their direct target molecule(s) and mechanism(s) remain unclear. We investigated the effect of naringenin, a major flavonoid found in citrus, on UVB‐induced MMP‐1 expression and identified its direct target. The HaCaT human skin keratinocyte cell line and 3‐dimensional (3‐D) human skin equivalent cultures were treated or not treated with naringenin for 1 hr before exposure to UVB. The mechanism and target(s) of naringenin were analysed by kinase assay and multiplex molecular assays. Dorsal skins of hairless mice were exposed to UVB 3 times per week, with a dose of irradiation that was increased weekly by 1 minimal erythema dose (MED; 45 mJ/cm2) to 4 MED over 15 weeks. Wrinkle formation, water loss and water content were then assessed. Naringenin suppressed UVB‐induced MMP‐1 expression and AP‐1 activity, and strongly suppressed UVB‐induced phosphorylation of Fos‐related antigen (FRA)‐1 at Ser265. Importantly, UVB irradiation‐induced FRA1 protein stability was reduced by treatment with naringenin, as well as with a mitogen‐activated protein kinase (MEK) inhibitor. Naringenin significantly suppressed UVB‐induced extracellular signal‐regulated kinase 2 (ERK2) activity and subsequently attenuated UVB‐induced phosphorylation of p90RSK by competitively binding with ATP. Constitutively active MEK (CA‐MEK) increased FRA1 phosphorylation and expression and also induced MMP‐1 expression, whereas dominant‐negative ERK2 (DN‐ERK2) had opposite effects. U0126, a MEK inhibitor, also decreased FRA1 phosphorylation and expression as well as MMP‐1 expression. The photoaging data obtained from mice clearly demonstrated that naringenin significantly inhibited UVB‐induced wrinkle formation, trans‐epidermal water loss and MMP‐13 expression. Naringenin exerts potent anti‐photoaging effects by suppressing ERK2 activity and decreasing FRA1 stability, followed by down‐regulation of AP‐1 transactivation and MMP‐1 expression.
A Novel Universal Cementation Technique for Implant‐Supported Crowns with Subgingival Margins
Authors: Bhushan Prem , Aras Meena A. , Chitre Vidya , Mysore Ashwin R. , Daswani Sohil R.
Published: February 2016

Restoration of implant crowns with subgingival margins has always been a challenge. If done precisely it leads to better treatment outcomes and prognosis. An incorrect technique and improper execution of the luting procedure are known to cause a high incidence of peri‐implant disease due to incomplete elimination of the luting agent. Deep subgingival abutment margins are difficult to recognize, and cement removal in these cases becomes complicated if the sulcus depth is greater than 3 mm. Irrespective of the type of instrument used to remove the excess cement, scratches on the abutment and some cement remnants are consistently noticed. Therefore elimination of excess luting agent before the prosthesis is inserted intraorally is considered an effective technique to prevent complications due to excess luting agent. This article presents a chairside universal technique for cementation of implant crowns on abutments with deep subgingival margins. This technique attempts to minimize the amount of excess cement in peri‐implant tissue.
Advance care planning in chronic kidney disease: A survey of current practice in Australia
Authors: Luckett Tim , Spencer Lucy , Morton Rachael L , Pollock Carol A , Lam Lawrence , Silvester William , Sellars Marcus , Detering Karen M , Butow Phyllis N , Tong Allison , Clayton Josephine M
Published: February 2016

Aim

Advance care planning (ACP) in nephrology is widely advocated but not always implemented. The aims of this study were to describe current ACP practice and identify barriers/facilitators and perceived need for health professional education and chronic kidney disease (CKD)‐specific approaches.

Methods

An anonymous cross‐sectional survey was administered online. Nephrology health professionals in Australia and New Zealand were recruited via professional societies, email lists and nephrology conferences. Multiple regression explored the influence of respondents' attributes on extent of involvement in ACP and willingness to engage in future.

Results

A total of 375 respondents included nephrologists (23%), nurses (65%), social workers (4%) and others (8%) with 54% indicated that ACP at their workplace was performed ad hoc and 61% poorly. Perceived barriers included patient/family discomfort (84%), difficulty engaging families (83%), lack of clinician expertise (83%) and time (82%), health professional discomfort (72%), cultural/language barriers (65%), lack of private space (61%) and lack of formal policy/procedures (60%). Respondents overwhelmingly endorsed the need for more dialysis‐specific ACP programs (96%) and education (95%). Whilst 85% thought ACP would be optimally performed by specially trained staff, comments emphasized that all clinicians should have a working proficiency. Respondents who were more willing to engage in future ACP tended to be non‐physicians (odds ratio (OR) 4.96, 95% confidence intervals (CI) 1.74–14.07) and reported a greater need for CKD‐specific ACP materials (OR 10.88, 95% CI 2.38–49.79).

Conclusion

Advance care planning in nephrology needs support through education and CKD‐specific resources. Endorsement by nephrologists is important. A multidisciplinary approach with a gradient of ACP expertise is also recommended.
High‐Potency Topical Steroids: An Effective Therapy for Chronic Scalp Inflammation in Rapp–Hodgkin Ectodermal Dysplasia
Authors: Theiler Martin , Frieden Ilona J.
Published: February 2016

Chronic erosive pustular dermatitis with a predilection for the scalp is a hallmark of ectodermal dysplasias (EDs) caused by mutations in TP63, including Rapp–Hodgkin and Hay–Wells EDs. It is among the most troublesome and symptomatic complications and is typically refractory to classic wound care approaches. We report two cases of Rapp–Hodgkin ED with refractory scalp erosions that markedly improved with the use of potent topical steroids. We also note marked similarities between this scalp inflammation and “erosive pustular dermatosis of the scalp,” a condition more typically found in elderly individuals with severe scalp sun damage, and speculate about possible shared pathogenetic mechanisms.
Neurovascular Stains in Two Girls with Neurofibromatosis 1
Authors: Crall Cary S. , Rork Jillian , Maguiness Sheliagh , Schmidt Birgitta , Gellis Stephen
Published: February 2016

We report two girls, ages 9 and 17 years, with a clinical diagnosis of neurofibromatosis 1 (NF‐1) who presented with ill‐defined, blanchable, erythematous patches on the dorsal feet and ankles. We hypothesized that these patches were a rare cutaneous finding in NF‐1 that exist on a clinical and histopathologic spectrum with previously described NF‐1 vascular lesions including blue–red macules and skin ulceration due to NF‐1 vasculopathy. We suggest that these lesions be called neurovascular stains (NVSs) to unify their clinical and histopathologic features.
Palisaded Neutrophilic Granulomatous Dermatitis in a Child with Juvenile Idiopathic Arthritis on Etanercept
Authors: Nguyen Tuyet A. , Celano Nicholas J. , Matiz Catalina
Published: February 2016

Palisaded neutrophilic granulomatous dermatitis (PNGD) is a rare neutrophilic dermatosis that may be associated with significant morbidity because of associated pruritus and pain. It is typically seen in adults with collagen vascular diseases, but may be associated with medications as well. PNGD is rarely reported in children. We describe a girl with polyarticular juvenile idiopathic arthritis who developed PNGD after administration of etanercept and demonstrated rapid and significant improvement upon treatment with topical triamcinolone 0.1% ointment.
Factors associated with the specific worries of childhood cancer survivors: Cross‐sectional survey in Japan
Authors: Ishida Yasushi , Higaki Takashi , Hayashi Mitsue , Inoue Fumiko , Ozawa Miwa
Published: February 2016

Background

Previous research has shown that adult childhood cancer survivors (CCS) have many worries. We re‐analyzed the employment data in order to identify these worries and their associated factors.

Methods

The participants were selected from the membership directory of Heart Link mutual‐aid health insurance, and recruited by the CCS Network. We conducted a cross‐sectional survey (a self‐rated questionnaire on employment) via post or email with a link to an Internet website. We investigated the association between CCS factors and the specific worries. The adjusted odds ratios (OR) for the associated factors with a specific worry were estimated on logistic regression analysis.

Results

A total of 240 questionnaires were collected by November 2012. One questionnaire was excluded because the answers were not provided by the CCS him/herself. The most common worries were health‐related problems (50%) and employment issues (40%), which were followed by his/her personality and life (23%) and self‐appearance (20%). Fifty (21%) out of 239 CCS answered no specific worry. The common consistent factor associated with worries was the presence of late effects. Of note was that the CCS worries were not associated with age at diagnosis or follow up, gender, educational achievement or marriage. The worry about employment issues was associated with economic status, disability qualification, and employment status.

Conclusions

The CCS worries were strongly affected by the presence of late effects. No significant association was noted between CCS worries and gender, age at diagnosis or follow up, or educational achievements. Economic status and disability qualification were associated with some worries.
Word to the Wise: Notes on a Black Feminist Metaphilosophy of Race
Authors: Dotson Kristie
Published: February 2016

It is not uncommon to ask a race and gender‐based question of a philosopher of race, only to hear ‘I do race, not gender’. To the ears of many Black feminists, this sounds, to be frank, utterly foolish. Here, I identify three metaphilosophical assumptions, i.e. the disaggregation, fundamentality and transcendental assumptions, that aid in underwriting the ability to use the statement, ‘I do race, not gender’, as a means for avoiding gender‐based questions in ‘race talks’. Then, I gesture to a reason to reject the fundamentality and transcendental assumptions, i.e. the promotion of intellectual slumming.
In Quality We Trust; but Quality of Life or Quality of Care?
Authors: Chen Shan Shan , Unruh Mark , Williams Mark
Published: February 2016

The ESRD program provides medical care to a diverse and medically complex patient population. The care for the ESRD patient population has become increasingly benchmarked with process of care measures. These measures include dialysis adequacy, anemia, nutrition, and vascular access outcomes. These process‐related dialysis measures may not improve the care of the individual patient as care relates to the individual's goals and values. There is also evidence that these process measures may not be causally related to quality of life, hospitalization, and survival. The adoption of patient‐reported outcomes may shift the balance toward more patient‐centered care. However, the extent to which mandated measures of health‐related quality of life and patient satisfaction result in improved outcomes remains unclear.
Dispositional aspects of body focus and idiopathic environmental intolerance attributed to electromagnetic fields (IEI‐EMF)
Authors: Dömötör Zsuzsanna , Doering Bettina K. , Köteles Ferenc
Published: February 2016

Body focus is often considered an undesirable characteristic from medical point of view as it amplifies symptoms and leads to higher levels of health anxiety. However, it is connected to mindfulness, well‐being and the sense of self in psychotherapy. The current study aimed to investigate the contribution of various body focus related constructs to acute and chronic generation and maintenance of medically unexplained symptoms (MUS). Thirty‐six individuals with idiopathic environmental intolerance to electromagnetic fields (IEI‐EMF) and 36 controls were asked to complete questionnaires assessing negative affect, worries about harmful effects of EMFs, health anxiety (HA), body awareness, and somatosensory amplification (SSA), and to report experienced symptoms evoked by a sham magnetic field. Body awareness, HA, SSA, and EMF‐related worries showed good discriminative power between individuals with IEI‐EMF and controls. Considering all variables together, SSA was the best predictor of IEI‐EMF. In the believed presence of a MF, people with IEI‐EMF showed higher levels of anxiety and reported more symptoms than controls. In the IEI‐EMF group, actual symptom reports were predicted by HA and state anxiety, while a reverse relationship between symptom reports and HA was found in the control group. Our findings show that SSA is a particularly important contributor to IEI‐EMF, probably because it is the most comprehensive factor in its aetiology. IEI‐EMF is associated with both a fear‐related monitoring of bodily symptoms and a non‐evaluative body focus. The identification of dispositional body focus may be relevant for the management of MUS.
A geometric view of the mean of a set of numbers
Authors: Sarkar Jyotirmoy , Rashid Mamunur
Published: February 2016

The sample mean is sometimes depicted as a fulcrum placed under the Dot plot. We provide an alternative geometric visualization of the sample mean using the empirical cumulative distribution function or the cumulative histogram data.
Erythrocyte invasion receptors for Plasmodium falciparum: new and old
Authors: Satchwell T. J.
Published: February 2016

Understanding the complex process by which the invasive form of the Plasmodium falciparum parasite, the merozoite, attaches to and invades erythrocytes as part of its blood stage life cycle represents a key area of research in the battle to combat malaria. Central to this are efforts to determine the identity of receptors on the host cell surface, their corresponding merozoite‐binding proteins and the functional relevance of these binding events as part of the invasion process. This review will provide an updated summary of studies identifying receptor interactions essential for or implicated in P. falciparum merozoite invasion of human erythrocytes, highlighting the recent identification of new receptors using groundbreaking high throughput approaches and with particular focus on the properties and putative involvement of the erythrocyte proteins targeted by these invasion pathways.
An order set and checklist improve physician transfusion ordering practices to mitigate the risk of transfusion‐associated circulatory overload
Authors: Tseng E. , Spradbrow J. , Cao X. , Callum J. , Lin Y.
Published: February 2016

Objectives and background

There are few studies of quality interventions to mitigate the risk of transfusion‐associated circulatory overload (TACO). Our aim was to reduce TACO risk in patients admitted to internal medicine at our hospital, by addressing gaps in transfusion practice.

Materials and methods

A 3‐month baseline audit of red blood cell (RBC) transfusion orders was conducted. An intervention consisting of a transfusion order set and physician checklist was developed and implemented based on identified gaps, followed by a 3‐month post‐intervention audit. Compliance with appropriateness criteria for RBC transfusion was ascertained, along with documentation of transfusion rate, diuretic usage and consent.

Results

A total of 97 transfusion orders from 68 inpatients and 95 orders from 62 inpatients were audited in the baseline and post‐intervention groups, respectively. Compliance with appropriateness criteria was similar pre‐ and post‐intervention (87 versus 85%, P = 0·81). Specification of transfusion rate improved (84 versus 98%, P < 0·01), and diuretics were appropriately ordered more frequently for patients with TACO risk factors (37 versus 64%, P < 0·01). Timing of diuretics shifted from between or post‐transfusion to pre‐transfusion (35 versus 86%, P < 0·01), without increases in hypokalemia or acute kidney injury. No case of TACO was observed during the study. Documentation of specific risks discussed during consent discussion improved (4 versus 23%, P < 0·01).

Conclusion

A checklist and order set are tools that can improve the quality of transfusion orders by increasing the judicious use of pre‐transfusion diuretics and augmenting the specification of transfusion rate. These interventions could be adapted to electronic order formats to improve transfusion safety.
The role of Orai–STIM calcium channels in melanocytes and melanoma
Authors: Stanisz Hedwig , Vultur Adina , Herlyn Meenhard , Roesch Alexander , Bogeski Ivan
Published: February 2016

Calcium signalling within normal and cancer cells regulates many important cellular functions such as migration, proliferation, differentiation and cytokine secretion. Store operated Ca2+ entry (SOCE) via the Ca2+ release activated Ca2+ (CRAC) channels, which are composed of the plasma membrane based Orai channels and the endoplasmic reticulum stromal interaction molecules (STIMs), is a major Ca2+ entry route in many cell types. Orai and STIM have been implicated in the growth and metastasis of multiple cancers; however, while their involvement in cancer is presently indisputable, how Orai–STIM‐controlled Ca2+ signals affect malignant transformation, tumour growth and invasion is not fully understood. Here, we review recent studies linking Orai–STIM Ca2+ channels with cancer, with a particular focus on melanoma. We highlight and examine key molecular players and the signalling pathways regulated by Orai and STIM in normal and malignant cells, we expose discrepancies, and we reflect on the potential of Orai–STIMs as anticancer drug targets. Finally, we discuss the functional implications of future discoveries in the field of Ca2+ signalling.

image
Teaching neurons to respond to placebos
Authors: Benedetti Fabrizio , Frisaldi Elisa , Carlino Elisa , Giudetti Lucia , Pampallona Alan , Zibetti Maurizio , Lanotte Michele , Lopiano Leonardo
Published: February 2016

Key points

We analysed the placebo response at the single‐neuron level in the thalamus of Parkinson patients to see the differences between first‐time administration of placebo and administration after pharmacological pre‐conditioning.

When the placebo was given for the first time, it induced neither clinical improvement, as assessed through muscle rigidity reduction at the wrist, nor neuronal changes in thalamic neurons.

However, if placebo was given after two, three or four prior administrations of an anti‐Parkinson drug, apomorphine, it produced both clinical and neuronal responses.

Both the magnitude and the duration of these placebo responses depended on the number of prior exposures to apomorphine, according to the rule: the greater the number of previous apomorphine administrations, the larger the magnitude and the longer the duration of the clinical and neuronal placebo responses.

These findings show that learning plays a crucial role in the placebo response and suggest that placebo non‐responders can be turned into placebo responders, with important clinical implications.

Placebos have been found to affect the patient's brain in several conditions, such as pain and motor disorders. For example, in Parkinson's disease, a placebo treatment induces a release of dopamine in the striatum and changes the activity of neurons in both thalamic and subthalamic nuclei. The present study shows that placebo administration for the first time induces neither clinical nor neuronal improvement in Parkinson patients who undergo implantation of electrodes for deep brain stimulation. However, this lack of placebo responsiveness can be turned into substantial placebo responses following previous exposure to repeated administrations of the anti‐Parkinson agent apomorphine. As the number of apomorphine administrations increased from one to four, both the clinical response and the neuronal activity in the ventral anterior and anterior ventrolateral thalamus increased. In fact, after four apomorphine exposures, placebo administration induced clinical responses that were as large as those to apomorphine, along with long‐lasting neuronal changes. These clinical placebo responses following four apomorphine administrations were again elicited after a re‐exposure to a placebo 24 h after surgery, but not after 48 h. These data indicate that learning plays a crucial role in placebo responsiveness and suggest that placebo non‐responders can be turned into responders, with important implications in the clinical setting.
A Probabilistic Crack Band Model for Quasibrittle Fracture
Authors: Le Jia-Liang , Eliáš Jan
Published: February 2016

This paper presents a new crack band model (CBM) for probabilistic analysis of quasibrittle fracture. The model is anchored by a probabilistic treatment of damage initiation, localization, and propagation. This model regularizes the energy dissipation of a single material element for the transition between damage initiation and localization. Meanwhile, the model also takes into account the probabilistic onset of damage localization inside the finite element (FE) for the case where the element size is larger than the crack band width. The random location of the localization band is related to the random material strength, whose statistics is described by a finite weakest link model. The present model is applied to simulate the probability distributions of the nominal strength of different quasibrittle structures. It is shown that for quasibrittle structures direct application of the conventional CBM for stochastic FE simulations would lead to mesh-sensitive results. To mitigate such mesh dependence, it is essential to incorporate the strain localization mechanism into the formulation of the sampling distribution functions of material constitutive parameters.
Experimental Investigation on Underwater Buckling of Thin-Walled Composite and Metallic Structures
Authors: Pinto Michael , Matos Helio , Gupta Sachin , Shukla Arun
Published: February 2016

An experimental study on the underwater buckling of composite and metallic tubes is conducted to evaluate and compare their collapse mechanics. Experiments are performed in a pressure vessel designed to provide constant hydrostatic pressure through the collapse. Filament-wound carbon-fiber/epoxy, glass/polyester (PE) tubes, and aluminum tubes are studied to explore the effect of material type on the structural failure. Three-dimensional digital image correlation (DIC) technique is used to capture the full-field deformation and velocities during the implosion event. Local pressure fields generated by the implosion event are measured using dynamic pressure transducers to evaluate the strength of the emitted pressure pulse. The results show that glass/PE tubes release the weakest pressure pulse and carbon/epoxy tubes release the strongest upon collapse. In each case, the dominating mechanisms of failure control the amount of flow energy released.
Resolving the Complexity of Human Skin Metagenomes Using Single-Molecule Sequencing
Authors: Tsai Yu-Chih , Conlan Sean , Deming Clayton ,   NISC Comparative Sequencing Program, Segre Julia A. , Kong Heidi H. , Korlach Jonas , Oh Julia
Published: February 2016

Deep metagenomic shotgun sequencing has emerged as a powerful tool to interrogate composition and function of complex microbial communities. Computational approaches to assemble genome fragments have been demonstrated to be an effective tool for
de novo
reconstruction of genomes from these communities. However, the resultant “genomes” are typically fragmented and incomplete due to the limited ability of short-read sequence data to assemble complex or low-coverage regions. Here, we use single-molecule, real-time (SMRT) sequencing to reconstruct a high-quality, closed genome of a previously uncharacterized
Corynebacterium simulans
and its companion bacteriophage from a skin metagenomic sample. Considerable improvement in assembly quality occurs in hybrid approaches incorporating short-read data, with even relatively small amounts of long-read data being sufficient to improve metagenome reconstruction. Using short-read data to evaluate strain variation of this
C. simulans
in its skin community at single-nucleotide resolution, we observed a dominant
C. simulans
strain with moderate allelic heterozygosity throughout the population. We demonstrate the utility of SMRT sequencing and hybrid approaches in metagenome quantitation, reconstruction, and annotation.

IMPORTANCE
The species comprising a microbial community are often difficult to deconvolute due to technical limitations inherent to most short-read sequencing technologies. Here, we leverage new advances in sequencing technology, single-molecule sequencing, to significantly improve reconstruction of a complex human skin microbial community. With this long-read technology, we were able to reconstruct and annotate a closed, high-quality genome of a previously uncharacterized skin species. We demonstrate that hybrid approaches with short-read technology are sufficiently powerful to reconstruct even single-nucleotide polymorphism level variation of species in this a community.
Genome-wide Annotation, Identification, and Global Transcriptomic Analysis of Regulatory or Small RNA Gene Expression in Staphylococcus aureus
Authors: Carroll Ronan K. , Weiss Andy , Broach William H. , Wiemels Richard E. , Mogen Austin B. , Rice Kelly C. , Shaw Lindsey N.
Published: February 2016

In
Staphylococcus aureus
, hundreds of small regulatory or small RNAs (sRNAs) have been identified, yet this class of molecule remains poorly understood and severely understudied. sRNA genes are typically absent from genome annotation files, and as a consequence, their existence is often overlooked, particularly in global transcriptomic studies. To facilitate improved detection and analysis of sRNAs in
S. aureus
, we generated updated GenBank files for three commonly used
S. aureus
strains (MRSA252, NCTC 8325, and USA300), in which we added annotations for >260 previously identified sRNAs. These files, the first to include genome-wide annotation of sRNAs in
S. aureus
, were then used as a foundation to identify novel sRNAs in the community-associated methicillin-resistant strain USA300. This analysis led to the discovery of 39 previously unidentified sRNAs. Investigating the genomic loci of the newly identified sRNAs revealed a surprising degree of inconsistency in genome annotation in
S. aureus
, which may be hindering the analysis and functional exploration of these elements. Finally, using our newly created annotation files as a reference, we perform a global analysis of sRNA gene expression in
S. aureus
and demonstrate that the newly identified
tsr25
is the most highly upregulated sRNA in human serum. This study provides an invaluable resource to the
S. aureus
research community in the form of our newly generated annotation files, while at the same time presenting the first examination of differential sRNA expression in pathophysiologically relevant conditions.

IMPORTANCE
Despite a large number of studies identifying regulatory or small RNA (sRNA) genes in
Staphylococcus aureus
, their annotation is notably lacking in available genome files. In addition to this, there has been a considerable lack of cross-referencing in the wealth of studies identifying these elements, often leading to the same sRNA being identified multiple times and bearing multiple names. In this work, we have consolidated and curated known sRNA genes from the literature and mapped them to their position on the
S. aureus
genome, creating new genome annotation files. These files can now be used by the scientific community at large in experiments to search for previously undiscovered sRNA genes and to monitor sRNA gene expression by transcriptome sequencing (RNA-seq). We demonstrate this application, identifying 39 new sRNAs and studying their expression during
S. aureus
growth in human serum.
Host RNA Packaging by Retroviruses: A Newly Synthesized Story
Authors: Eckwahl Matthew J. , Telesnitsky Alice , Wolin Sandra L.
Published: February 2016

A fascinating aspect of retroviruses is their tendency to nonrandomly incorporate host cell RNAs into virions. In addition to the specific tRNAs that prime reverse transcription, all examined retroviruses selectively package multiple host cell noncoding RNAs (ncRNAs). Many of these ncRNAs appear to be encapsidated shortly after synthesis, before assembling with their normal protein partners. Remarkably, although some packaged ncRNAs, such as pre-tRNAs and the spliceosomal U6 small nuclear RNA (snRNA), were believed to reside exclusively within mammalian nuclei, it was demonstrated recently that the model retrovirus murine leukemia virus (MLV) packages these ncRNAs from a novel pathway in which unneeded nascent ncRNAs are exported to the cytoplasm for degradation. The finding that retroviruses package forms of ncRNAs that are rare in cells suggests several hypotheses for how these RNAs could assist retrovirus assembly and infectivity. Moreover, recent experiments in several laboratories have identified additional ways in which cellular ncRNAs may contribute to the retrovirus life cycle. This review focuses on the ncRNAs that are packaged by retroviruses and the ways in which both encapsidated ncRNAs and other cellular ncRNAs may contribute to retrovirus replication.
Two Cyanobacterial Photoreceptors Regulate Photosynthetic Light Harvesting by Sensing Teal, Green, Yellow, and Red Light
Authors: Wiltbank Lisa B. , Kehoe David M.
Published: February 2016

The genomes of many photosynthetic and nonphotosynthetic bacteria encode numerous phytochrome superfamily photoreceptors whose functions and interactions are largely unknown. Cyanobacterial genomes encode particularly large numbers of phytochrome superfamily members called cyanobacteriochromes. These have diverse light color-sensing abilities, and their functions and interactions are just beginning to be understood. One of the best characterized of these functions is the regulation of photosynthetic light-harvesting antenna composition in the cyanobacteriumFremyella diplosiphonby the cyanobacteriochrome RcaE in response to red and green light, a process known as chromatic acclimation. We have identified a new cyanobacteriochrome named DpxA that maximally senses teal (absorption maximum, 494 nm) and yellow (absorption maximum, 568 nm) light and represses the accumulation of a key light-harvesting protein called phycoerythrin, which is also regulated by RcaE during chromatic acclimation. Like RcaE, DpxA is a two-component system kinase, although these two photoreceptors can influence phycoerythrin expression through different signaling pathways. The peak responsiveness of DpxA to teal and yellow light provides highly refined color discrimination in the green spectral region, which provides important wavelengths for photosynthetic light harvesting in cyanobacteria. These results redefine chromatic acclimation in cyanobacteria and demonstrate that cyanobacteriochromes can coordinately impart sophisticated light color sensing across the visible spectrum to regulate important photosynthetic acclimation processes.

IMPORTANCEThe large number of cyanobacteriochrome photoreceptors encoded by cyanobacterial genomes suggests that these organisms are capable of extremely complex light color sensing and responsiveness, yet little is known about their functions and interactions. Our work uncovers previously undescribed cooperation between two photoreceptors with very different light color-sensing capabilities that coregulate an important photosynthetic light-harvesting protein in response to teal, green, yellow, and red light. Other cyanobacteriochromes that have been shown to interact functionally sense wavelengths of light that are close to each other, which makes it difficult to clearly identify their physiological roles in the cell. Our finding of two photoreceptors with broad light color-sensing capabilities and clearly defined physiological roles provides new insights into complex light color sensing and its regulation.
Methods of a large prospective, randomised, open-label, blinded end-point study comparing morning versus evening dosing in hypertensive patients: the Treatment In Morning versus Evening (TIME) study
Authors: Rorie David A , Rogers Amy , Mackenzie Isla S , Ford Ian , Webb David J , Willams Bryan , Brown Morris , Poulter Neil , Findlay Evelyn , Saywood Wendy , MacDonald Thomas M
Published: February 2016

Introduction

Nocturnal blood pressure (BP) appears to be a better predictor of cardiovascular outcome than daytime BP. The BP lowering effects of most antihypertensive therapies are often greater in the first 12 h compared to the next 12 h. The Treatment In Morning versus Evening (TIME) study aims to establish whether evening dosing is more cardioprotective than morning dosing.

Methods and analysis

The TIME study uses the prospective, randomised, open-label, blinded end-point (PROBE) design. TIME recruits participants by advertising in the community, from primary and secondary care, and from databases of consented patients in the UK. Participants must be aged over 18 years, prescribed at least one antihypertensive drug taken once a day, and have a valid email address. After the participants have self-enrolled and consented on the secure TIME website (http://www.timestudy.co.uk) they are randomised to take their antihypertensive medication in the morning or the evening. Participant follow-ups are conducted after 1 month and then every 3 months by automated email. The trial is expected to run for 5 years, randomising 10 269 participants, with average participant follow-up being 4 years. The primary end point is hospitalisation for the composite end point of non-fatal myocardial infarction (MI), non-fatal stroke (cerebrovascular accident; CVA) or any vascular death determined by record-linkage. Secondary end points are: each component of the primary end point, hospitalisation for non-fatal stroke, hospitalisation for non-fatal MI, cardiovascular death, all-cause mortality, hospitalisation or death from congestive heart failure. The primary outcome will be a comparison of time to first event comparing morning versus evening dosing using an intention-to-treat analysis. The sample size is calculated for a two-sided test to detect 20% superiority at 80% power.

Ethics and dissemination

TIME has ethical approval in the UK, and results will be published in a peer-reviewed journal.

Trial registration number

UKCRN17071; Pre-results.
The Irish National Adverse Events Study (INAES): the frequency and nature of adverse events in Irish hospitals—a retrospective record review study
Authors: Rafter Natasha , Hickey Anne , Conroy Ronan M , Condell Sarah , O'Connor Paul , Vaughan David , Walsh Gillian , Williams David J
Published: February 2016

Introduction

Irish healthcare has undergone extensive change recently with spending cuts and a focus on quality initiatives; however, little is known about adverse event occurrence.

Objective

To assess the frequency and nature of adverse events in Irish hospitals.

Methods

1574 (53% women, mean age 54 years) randomly selected adult inpatient admissions from a sample of eight hospitals, stratified by region and size, across the Republic of Ireland in 2009 were reviewed using two-stage (nurse review of patient charts, followed by physician review of triggered charts) retrospective chart review with electronic data capture. Results were weighted to reflect the sampling strategy. The impact on adverse event rate of differing application of international adverse event criteria was also examined.

Results

45% of charts were triggered. The prevalence of adverse events in admissions was 12.2% (95% CI 9.5% to 15.5%), with an incidence of 10.3 events per 100 admissions (95% CI 7.5 to 13.1). Over 70% of events were considered preventable. Two-thirds were rated as having a mild-to-moderate impact on the patient, 9.9% causing permanent impairment and 6.7% contributing to death. A mean of 6.1 added bed days was attributed to events, representing an expenditure of €5550 per event. The adverse event rate varied substantially (8.6%–17.0%) when applying different published adverse event eligibility criteria.

Conclusions

This first study of adverse events in Ireland reports similar rates to other countries. In a time of austerity, adverse events in adult inpatients were estimated to cost over €194 million. These results provide important baseline data on the adverse event burden and, alongside web-based chart review, provide an incentive and methodology to monitor future patient-safety initiatives.
The glucoregulatory response to high-intensity aerobic exercise following training in rats with insulin-treated type 1 diabetes mellitus
Authors: McDonald Matthew W. , Murray Michael R. , Grise Kenneth N. , Olver T. Dylan , Dey Adwitia , Shoemaker J. Kevin , Noble Earl G. , Melling C.W. James
Published: February 2016

An acute bout of exercise elicits a rapid, potentially deleterious, reduction in blood glucose in patients with type 1 diabetes mellitus (T1DM). In the current study, we examined whether a 10-week aerobic training program could alleviate the rapid exercise-associated reduction in blood glucose through changes in the glucoregulatory hormonal response or increased hepatic glycogen storage in an insulin-treated rat model of T1DM. Thirty-two male Sprague–Dawley rats were divided evenly into 4 groups: non-T1DM sedentary (C) (n = 8), non-T1DM exercised (CX) (n = 8), T1DM sedentary (D) (n = 8), and T1DM exercised (DX) (n = 8). Exercise training consisted of treadmill running for 5 days/week (1 h, 27 m/min, 6% grade) for 10 weeks. T1DM was induced by multiple streptozotocin injections (20 mg/kg) followed by implantation of subcutaneous insulin pellets. At week 1, an acute exercise bout led to a significant reduction in blood glucose in DX (p < 0.05), whereas CX exhibited an increase in blood glucose (p < 0.05). During acute exercise, serum epinephrine was increased in both DX and CX (p < 0.05), whereas serum glucagon was increased during recovery only in CX (p < 0.01). Following aerobic training in DX, the exercise-mediated reduction in blood glucose remained; however, serum glucagon increased to the same extent as in CX (p < 0.05). DX exhibited significantly less hepatic glycogen (p < 0.001) despite elevations in glycogenic proteins in the liver (p < 0.05). Elevated serum epinephrine and decreased hepatic adrenergic receptor expression were also evident in DX (p < 0.05). In summary, despite aerobic training in DX, abrupt blood glucose reductions and hepatic glycogen deficiencies were evident. These data suggest that sympathetic overactivity may contribute to deficiencies in hepatic glycogen storage.