bluuebunny/crossref_metadata_2025 huggingface dataset:
German EstSmoke: estimating adult smoking‐related costs and consequences of smoking cessation for Germany
Authors: Sonntag Diana , Gilbody Simon , Winkler Volker , Ali Shehzad
Published: July 2017

Aims

We compared predicted life‐time health‐care costs for current, never and ex‐smokers in Germany under the current set of tobacco control polices. We compared these economic consequences of the current situation with an alternative in which Germany were to implement more comprehensive tobacco control policies consistent with the World Health Organization (WHO) Framework Convention for Tobacco Control (FCTC) guidelines.

Design

German EstSmoke, an adapted version of the UK EstSmoke simulation model, applies the Markov modelling approach. Transition probabilities for (re‐)currence of smoking‐related diseases were calculated from large German disease‐specific registries and the German Health Update (GEDA 2010). Estimations of both health‐care costs and effect sizes of smoking cessation policies were taken from recent German studies and discounted at 3.5%/year.

Setting

Germany.

Participants

German population of prevalent current, never and ex‐smokers in 2009.

Measurement

Life‐time cost and outcomes in current, never and ex‐smokers.

Findings

If tobacco control policies are not strengthened, the German smoking population will incur €41.56 billion life‐time excess costs compared with never smokers. Implementing tobacco control policies consistent with WHO FCTC guidelines would reduce the difference of life‐time costs between current smokers and ex‐smokers by at least €1.7 billion.

Conclusions

Modelling suggests that the life‐time healthcare costs of people in Germany who smoke are substantially greater than those of people who have never smoked. However, more comprehensive tobacco control policies could reduce health‐care expenditures for current smokers by at least 4%.
A randomised controlled trial of oral chloral hydrate vs. intranasal dexmedetomidine before computerised tomography in children
Authors: Yuen V. M. , Li B. L. , Cheuk D. K. , Leung M. K. M. , Hui T. W. C. , Wong I. C. , Lam W. W. , Choi S. W. , Irwin M. G.
Published: July 2017

Chloral hydrate is commonly used to sedate children for painless procedures. Children may recover more quickly after sedation with dexmedetomidine, which has a shorter half‐life. We randomly allocated 196 children to chloral hydrate syrup 50 mg.kg−1 and intranasal saline spray, or placebo syrup and intranasal dexmedetomidine spray 3 μg.kg−1, 30 min before computerised tomography studies. More children resisted or cried after drinking chloral hydrate syrup than placebo syrup, 72 of 107 (67%) vs. 42 of 87 (48%), p = 0.009, but there was no difference after intranasal saline vs. dexmedetomidine, 49 of 107 (46%) vs. 40 of 87 (46%), p = 0.98. Sedation was satisfactory in 81 of 107 (76%) children after chloral hydrate and 64 of 87 (74%) children after dexmedetomidine, p = 0.74. Of the 173 children followed up for at least 4 h after discharge, 38 of 97 (39%) had recovered normal function after chloral hydrate and 32 of 76 (42%) after dexmedetomidine, p = 0.76. Six children vomited after chloral hydrate syrup and placebo spray vs. none after placebo syrup and dexmedetomidine spray, p = 0.03.
Long‐term effectiveness of the preoperative smoking cessation programme at Western Health
Authors: Taylor Hugh , Karahalios Amalia , Bramley David
Published: July 2017

Background

Smoking is associated with adverse effects in the perioperative period, including elevated risk of death. The perioperative period provides an opportunity to engage with patients who are smokers to encourage smoking cessation, often referred to as a ‘teachable moment’. We developed a smoking intervention model for the pre‐admission clinic (PAC) at Western Health, Victoria, Australia. This case series aimed to assess the impact of the smoking intervention model, which is standard of care, on the participant's smoking habits over four time points.

Methods

We enrolled 50 consecutive participants for elective surgery who were smokers and had attended PAC at Western Health, Footscray. All smokers were offered a standard intervention package to address their smoking. Participants underwent a brief interview to elicit their current smoking behaviour on their day of surgery, 3 and 12 months post‐operatively.

Results

We found a reduction at each time point post‐intervention in the average number of cigarettes smoked per day by all participants with a 43% reduction at 12 months compared with PAC. We found that the number of participants who had quit increased at each time point, with 29% abstinent at 12 months post‐operatively. At 12 months, we found 71% of participants had either quit or reduced the number of cigarettes smoked compared with the amount reported at PAC.

Conclusion

This study adds to the evidence that a simple intervention preoperatively can contribute to long‐term changes in smoking behaviour.
Sense organs in Pycnogonida: A review
Authors: Lehmann Tobias , Heß Martin , Melzer Roland R.
Published: July 2017

The Pycnogonida or sea spiders are exclusively marine invertebrates, numbering about 1,300 described species worldwide. Given their remarkable position in phylogeny as basal chelicerates or even basal euarthropods, the structure of their sense organs can reveal important characters, which—in a comparative framework—provide arguments to phylogenetic discussions and help to develop scenarios of evolutionary transformations. This review summarizes current knowledge and presents new original data on the sense organs in pycnogonids, that is, the eyes, the lateral sense organs and the ciliary or sensillar sense organs. Except for the eyes, there are not many detailed studies available. The ultrastructure of the R‐cells of the four eyes located on the ocular tubercle is described as “pseudoinverted”. The eyes are innervated to two visual neuropils located in the protocerebrum. The features of the lateral sense organ, also located on the ocular tubercle, are hitherto not conclusively resolved, a chemo‐ or thermoreceptive function is suggested. Finally, an overview of the various ciliary or sensillar sense organs distributed all over the body is given and the fine structure of branched setae is shown for the first time. The morphology of the sense organs of pycnogonids is compared with that of other arthropod taxa and assessed against the background of current theories of arthropod evolution.
Population pharmacokinetics and exposure–response of trastuzumab emtansine in advanced breast cancer previously treated with ≥2 HER2‐targeted regimens
Authors: Chen Shang‐Chiung , Quartino Angelica , Polhamus Daniel , Riggs Matthew , French Jonathan , Wang Xin , Vadhavkar Shweta , Smitt Melanie , Hoersch Silke , Strasak Alexander , Jin Jin Yan , Girish Sandhya , Li Chunze
Published: July 2017

Aims

We conducted population pharmacokinetic (PopPK) and exposure–response analyses for trastuzumab emtansine (T‐DM1), to assess the need for T‐DM1 dose optimization in patients with low exposure by using TH3RESA [A Study of Trastuzumab Emtansine in Comparison With Treatment of Physician's Choice in Patients With human epidermal growth factor receptor 2 (HER2)‐positive Breast Cancer Who Have Received at Least Two Prior Regimens of HER2‐directed Therapy] study data (NCT01419197). The randomized phase III TH3RESA study investigated T‐DM1 vs. treatment of physician's choice (TPC) in patients with heavily pretreated HER2‐positive advanced breast cancer.

Methods

We compared a historical T‐DM1 PopPK model with T‐DM1 pharmacokinetics in TH3RESA and performed exposure–response analyses using model‐predicted cycle 1 maximum concentration (Cmax), cycle 1 minimum concentration (Cmin) and area under the concentration–time curve at steady state (AUCss). Kaplan–Meier analyses [overall survival (OS), progression‐free survival (PFS)] and logistic regression [overall response rate (ORR), safety] were stratified by T‐DM1 exposure metrics. Survival hazard ratios (HRs) in the lowest exposure quartile (Q1) of cycle 1 Cmin were compared with matched TPC‐treated patients.

Results

T‐DM1 concentrations in TH3RESA were described well by the historical PopPK model. Patients with higher cycle 1 Cmin and AUCss exhibited numerically longer median OS and PFS and higher ORR than patients with lower exposure. Exposure–response relationships were less evident for cycle 1 Cmax. No relationship between exposure and safety was identified. HRs for the comparison of T‐DM1‐treated patients in the Q1 subgroup with matched TPC‐treated patients were 0.96 [95% confidence interval (CI) 0.63, 1.47] for OS and 0.92 (95% CI 0.64, 1.32) for PFS.

Conclusions

Exposure–response relationships for efficacy were inconsistent across exposure metrics. HRs for survival in patients in the lowest T‐DM1 exposure quartile vs. matched TPC‐treated patients suggest that, compared with TCP, the approved T‐DM1 dose is unlikely to be detrimental to patients with low exposure.
Maternal SSRI discontinuation, use, psychiatric disorder and the risk of autism in children: a meta‐analysis of cohort studies
Authors: Kaplan Yusuf Cem , Keskin‐Arslan Elif , Acar Selin , Sozmen Kaan
Published: July 2017

We undertook an exclusive meta‐analysis of cohort studies investigating the possible link between prenatal selective serotonin reuptake inhibitor (SSRI) exposure and autism spectrum disorders (ASD) in children to further investigate our previous suggestion of confounding by indication. The point estimates regarding the following cohorts were extracted and pooled: (1) pregnant women who discontinued SSRI until 3 months before pregnancy; (2) pregnant women who were exposed to SSRI during pregnancy; and (3) pregnant women with maternal psychiatric disorder but no exposure to SSRI during pregnancy. Although the pooled point estimate of the first cohort showed a trend for increase, it did not reach significance. The pooled point estimates of the latter cohorts showed a significant association with ASD which strengthens our previous suggestion of confounding by indication. Future studies should be adequately designed to differentiate whether the previously suggested association is a result of maternal psychiatric disorder or SSRI exposure or both.
Incorporating Patient Preferences into Estimation of Optimal Individualized Treatment Rules
Authors: Butler Emily L. , Laber Eric B. , Davis Sonia M. , Kosorok Michael R.
Published: July 2017

Precision medicine seeks to provide treatment only if, when, to whom, and at the dose it is needed. Thus, precision medicine is a vehicle by which healthcare can be made both more effective and efficient. Individualized treatment rules operationalize precision medicine as a map from current patient information to a recommended treatment. An optimal individualized treatment rule is defined as maximizing the mean of a pre-specified scalar outcome. However, in settings with multiple outcomes, choosing a scalar composite outcome by which to define optimality is difficult. Furthermore, when there is heterogeneity across patient preferences for these outcomes, it may not be possible to construct a single composite outcome that leads to high-quality treatment recommendations for all patients. We simultaneously estimate the optimal individualized treatment rule for all composite outcomes representable as a convex combination of the (suitably transformed) outcomes. For each patient, we use a preference elicitation questionnaire and item response theory to derive the posterior distribution over preferences for these composite outcomes and subsequently derive an estimator of an optimal individualized treatment rule tailored to patient preferences. We prove that as the number of subjects and items on the questionnaire diverge, our estimator is consistent for an oracle optimal individualized treatment rule wherein each patient's preference is known a priori. We illustrate the proposed method using data from a clinical trial on antipsychotic medications for schizophrenia.
Transumbilical laparoendoscopic single‐site radical prostatectomy and cystectomy with the aid of a transurethral port: a feasibility study
Authors: Su Jian , Zhu Qingyi , Yuan Lin , Zhang Yang , Zhang Qingling , Wei Yunfei
Published: July 2017

Objective

To describe the surgical technique and report early outcomes of transurethral assisted laparoendoscopic single‐site (LESS) radical prostatectomy (RP) and LESS radical cystectomy (RC) in a single institution.

Materials and Methods

Between December 2014 and March 2016, a total of 114 LESS RPs and RCs were performed, comprising 68 LESS RPs, 38 LESS RCs with cutaneous ureterostomy (CU) and eight LESS RCs with orthotopic ileal neobladder (OIN). Access was achieved via a single‐port, with four channels placed through a transumblical incision. After the apex of prostate was separated from the urethra, a self‐developed port (‘Zhu's port’) was inserted through the urethra to facilitate resection of prostate and urethrovesical anastomosis. The peri‐operative and postoperative data were collected and analysed retrospectively. Patients were followed up postoperatively for evidence of long‐term side effects.

Results

All the procedures were completed successfully. No conversion to conventional laparoscopic surgery was necessary. For LESS RP, the average operating time was 152 min. Estimated blood loss was 117 mL. The mean hospital stay was 16.4 days after surgery. For LESS RC with CU and LESS RC with OIN, the mean operating times were 215 and 328 min, mean estimated blood loss was 175 and 252 mL, and mean hospital stay was 9.4 and 18.2 days, respectively. Six patients required blood transfusion (5.26%). Intra‐operative complications occurred in two patients (1.75%), and postoperative complications in nine (7.89%). Fourteen out of 68 (20.6%) patients who underwent LESS RP had positive surgical margins. Follow‐up ranged from 10 to 30.6 months. In the prostate cancer cases, good urinary control was observed in 35.3%, 97.1% and 100% of patients at 1, 6 and 12 months after the operation, respectively, while biochemical recurrence was observed in 11.8% patients. In the bladder cancer cases, two patients had local recurrence and two patients had distant metastasis.

Conclusion

Our results showed that LESS RP and LESS RC are feasible and safe with the aid of a transurethral port. Operating through the transurethral port might overcome the challenges posed by the single‐port laparoscopic approach.
The role of pre‐existing structures during rifting, continental breakup and transform system development, offshore West Greenland
Authors: Peace Alexander , McCaffrey Ken , Imber Jonathan , van Hunen Jeroen , Hobbs Richard , Wilson Robert
Published: July 2017

Continental breakup between Greenland and North America produced the small oceanic basins of the Labrador Sea and Baffin Bay, which are connected via the Davis Strait, a region mostly comprised of continental crust. This study contributes to the debate regarding the role of pre‐existing structures on rift development in this region using seismic reflection data from the Davis Strait data to produce a series of seismic surfaces, isochrons and a new offshore fault map from which three normal fault sets were identified as (i) NE‐SW, (ii) NNW‐SSE and (iii) NW‐SE. These results were then integrated with plate reconstructions and onshore structural data allowing us to build a two‐stage conceptual model for the offshore fault evolution in which basin formation was primarily controlled by rejuvenation of various types of pre‐existing structures. During the first phase of rifting between at least Chron 27 (ca. 62 Ma; Palaeocene), but potentially earlier, and Chron 24 (ca. 54 Ma; Eocene) faulting was primarily controlled by pre‐existing structures with oblique normal reactivation of both the NE‐SW and NW‐SE structural sets in addition to possible normal reactivation of the NNW‐SSE structural set. In the second rifting stage between Chron 24 (ca. 54 Ma; Eocene) and Chron 13 (ca. 35 Ma; Oligocene), the sinistral Ungava transform fault system developed due to the lateral offset between the Labrador Sea and Baffin Bay. This lateral offset was established in the first rift stage possibly due to the presence of the Nagssugtoqidian and Torngat terranes being less susceptible to rift propagation. Without the influence of pre‐existing structures the manifestation of deformation cannot be easily explained during either of the rifting phases. Although basement control diminished into the post‐rift, the syn‐rift basins from both rift stages continued to influence the location of sedimentation possibly due to differential compaction effects. Variable lithospheric strength through the rifting cycle may provide an explanation for the observed diminishing role of basement structures through time.
Novel menadione hybrids: Synthesis, anticancer activity, and cell‐based studies
Authors: Prasad Chakka Vara , Nayak Vadithe Lakshma , Ramakrishna Sistla , Mallavadhani Uppuluri Venkata
Published: July 2017

A series of novel menadione‐based triazole hybrids were designed and synthesized by employing copper‐catalyzed azide‐alkyne cycloaddition (CuAAC). All the synthesized hybrids were characterized by their spectral data (1H NMR, 13C NMR, IR, and HRMS). The synthesized compounds were evaluated for their anticancer activity against five selected cancer cell lines including lung (A549), prostate (DU‐145), cervical (Hela), breast (MCF‐7), and mouse melanoma (B‐16) using MTT assay. The screening results showed that majority of the synthesized compounds displayed significant anticancer activity. Among the tested compounds, the triazoles 5 and 6 exhibited potent activity against all cell lines. In particular, compound 6 showed higher potency than the standard tamoxifen and parent menadione against MCF‐7 cell line. Flow cytometric analysis revealed that compound 6 arrested cell cycle at G0/G1 phase and induced apoptotic cell death which was further confirmed by Hoechst staining, measurement of mitochondrial membrane potential (ΔΨm) and Annexin‐V‐FITC assay. Thus, compound 6 can be considered as lead molecule for further development as potent anticancer therapeutic agent.
Molecular analysis of brazilian patients with combined pituitary hormone deficiency and orthotopic posterior pituitary lobe reveals eight different PROP1 alterations with three novel mutations
Authors: Madeira Joao LO , Nishi Mirian Y , Nakaguma Marilena , Benedetti Anna F , Biscotto Isabela Peixoto , Fernandes Thamiris , Pequeno Thiago , Figueiredo Thalita , Franca Marcela M , Correa Fernanda A , Otto Aline P , Abrão Milena , Miras Mirta B , Santos Silvana , Jorge Alexander AL , Costalonga Everlayny F , Mendonca Berenice B , Arnhold Ivo JP , Carvalho Luciani R
Published: July 2017

Background

Mutations in PROP1, HESX1 and LHX3 are associated with combined pituitary hormone deficiency (CPHD) and orthotopic posterior pituitary lobe (OPP).

Objective

To identify mutations in PROP1, HESX1 and LHX3 in a large cohort of patients with CPHD and OPP (35 Brazilian, two Argentinian).

Design and Methods

We studied 23 index patients with CPHD and OPP (six familial and 17 sporadic) as well as 14 relatives. PROP1 was sequenced by the Sanger method in all except one sporadic case studied using a candidate gene panel. Multiplex ligation‐dependent probe amplification (MLPA) was applied to one familial case in whom PROP1 failed to amplify by PCR. In the 13 patients without PROP1 mutations, HESX1 and LHX3 were sequenced by the Sanger method.

Results

We identified PROP1 mutations in 10 index cases. Three mutations were novel: one affecting the initiation codon (c.1A>G) and two affecting splicing sites, c.109+1G>A and c.342+1G>C. The known mutations, c.150delA (p.Arg53Aspfs*112), c.218G>A (p.Arg73His), c.263T>C (p.Phe88Ser) and c.301_302delAG (p.Leu102Cysfs*8), were also detected. MLPA confirmed complete PROP1 deletion in one family. We did not identify HESX1 and LHX3 mutations by Sanger.

Conclusion

PROP1 mutations are a prevalent cause of congenital CPHD with OPP, and therefore, PROP1 sequencing must be the first step of molecular investigation in patients with CPHD and OPP, especially in populations with a high frequency of PROP1 mutations. In the absence of mutations, massively parallel sequencing is a promising approach. The high prevalence and diversity of PROP1 mutations is associated with the ethnic background of this cohort.
Implant treatment in pharmacologically immunosuppressed liver transplant patients: A prospective‐controlled study
Authors: Paredes Víctor , López‐Pintor Rosa María , Torres Jesús , de Vicente Juan Carlos , Sanz Mariano , Hernández Gonzalo
Published: July 2017

Objectives

The main objective of this prospective study was to evaluate the long‐term outcome of implant therapy in liver transplant patients (LTP). The secondary goal was to assess several implant‐ and patient‐dependent variables, such as peri‐implantitis (PI), peri‐implant mucositis (PIM), bone loss (BL), and immediate postoperative complications.

Material and methods

Two groups, including 16 pharmacologically immunosuppressed LTP and 16 matched controls, received 52 and 54 implants, respectively, between 1999 and 2008. After evaluating the postoperative healing, a mean follow‐up of more than 8 years was carried out, and radiographic, clinical, and periodontal parameters were recorded to evaluate implant survival and implant‐ and patient‐dependent outcomes.

Results

The early postsurgical complications were similar in both groups. Implant survival rate was 100% in the LTP group and 98.15% in the CG. PIM was diagnosed in 35.42% of the implants and 64.29% of the patients of LTP group (LTPG) and in 43.40% of the implants and 56.25% of the patients in the CG. PI was detected in 4.17% of the implants and 7.10% of the patients in the LTPG and in 9.43% of the implants and 18.80% of the patients in the CG.

Conclusion

Pharmacologically immunosuppression in liver transplant patients was not a risk factor for implant failure, nor for the incidence of peri‐implant diseases. Liver transplant is not a contraindication for dental implant treatment, although these patients should be carefully monitored during follow‐up care.
Downregulation of DEC1 contributes to the neurotoxicity induced by MPP+ by suppressing PI3K/Akt/GSK3β pathway
Authors: Zhu Zhu , Wang Yu‐Wen , Ge Ding‐Hao , Lu Ming , Liu Wei , Xiong Jing , Hu Gang , Li Xiao‐Ping , Yang Jian
Published: July 2017

Aim

Differentiated embryonic chondrocyte gene 1 (DEC1) is involved in the neuronal differentiation and development. The aim of this study is to investigate the role of DEC1 in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPP+)‐induced PD model.

Methods

The location of DEC1 and tyrosine hydroxylase (TH)‐positive neurons were detected by immunofluorescence. 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced mouse subacute model of PD was established to evaluate the change of DEC1 expression in midbrain. Then, SH‐SY5Y cells were used to investigate the role of DEC1 in MPP+‐induced neurotoxicity.

Results

We showed that the co‐expressed DEC1 and TH neurons took up more than 80% of the expressed TH neurons in the midbrain of mice. DEC1/TH double‐positive neurons decreased by 40.6% in SNpc and 28.8% in VTA of MPTP‐injured mice. Consistently, DEC1, TH and dopamine transporter (DAT) expression decreased in the midbrain of MPTP mice. In SY‐SY5Y cells, MPP+ significantly suppressed DEC1 expression and increased the cleaved caspase 3/caspase 3 and Bax/Bcl‐2. DEC1 overexpression relieved, whereas DEC1 knockdown aggravated MPP+‐induced cytotoxicity. Likewise, DEC1 overexpression and knockdown inversely regulated the expression of β‐catenin and PI3Kp110α (PIK3CA), an essential role in Wnt/β‐catenin and PI3K/Akt signaling pathways. Interestingly, LY294002, an inhibitor of PI3K/Akt signaling, aggravated, whereas LiCl, an activator of Wnt/β‐catenin signaling, abolished the reduction in DEC1 by MPP+. It is established that these two pathways are interconnected by the phosphorylation status of GSK3β. DEC1 overexpression increased but MPP+ and DEC1 knockdown decreased GSK3β phosphorylation.

Conclusion

Downregulation of DEC1 contributes to MPP+‐induced neurotoxicity by suppressing PI3K/Akt/GSK3β pathway.
Sleep duration and progression to diabetes in people with prediabetes defined by HbA1c concentration
Authors: Kim C.‐W. , Chang Y. , Sung E. , Ryu S.
Published: July 2017

Aims

To evaluate the association between sleep duration and the risk of progression to diabetes among people with prediabetes, defined by HbA1c values.

Methods

We conducted a cohort study in 17 983 adults who underwent health check‐up examinations, including assessments of sleep duration and quality. Diabetes was defined as either HbA1c ≥48 mmol/mol (6.5%), or the use of antidiabetic medication. Time‐dependent proportional hazards models were used to evaluate the association between sleep duration and the risk of progression to diabetes.

Results

During 31,582 person‐years of follow‐up, 664 incident cases of diabetes were identified; the incidence rate was 21.0 per 1000 person‐years. The multivariate adjusted hazard ratios for progression to diabetes in people with sleep durations of ≤5, 6 and ≥8 h compared with 7 h were 1.68 (95% CI 1.30–2.16), 1.44 (95% CI 1.17–1.76) and 1.23 (95% CI 0.85–1.78), respectively (P for quadratic trend <0.001). This association was partially mediated by biomarkers of adiposity, fatty liver and insulin resistance.

Conclusion

In this large study in young and middle‐aged adults with prediabetes, we found an association between short sleep duration and the risk of progression to diabetes. Our findings suggest that sufficient sleep duration is important for delaying or preventing the progression of prediabetes to diabetes.
Urban “slums” and social mobility
Authors: Turok Ivan , Budlender Joshua , Visagie Justin
Published: July 2017

Informal urban settlements determine the wellbeing of a large section of global humanity. Yet there has been little research on their role in facilitating social mobility. In theory such settlements may foster human progress by linking rural–urban migrants to the services, contacts and livelihoods concentrated in cities. The article uses longitudinal data for South Africa to explore the magnitude of social progression among people living within informal settlements compared with rural areas and formal urban areas. It finds that there may be some advantage from living in an informal settlement compared with a rural area, but the effect is not strong. The impact may be larger in the more prosperous Gauteng city‐region than in other urban regions.
Strain‐related pathogenicity in Diplodia corticola
Authors: Félix C. , Pinto G. , Amaral J. , Fernandes I. , Alves A. , Esteves A. C.
Published: July 2017

Diplodia corticola is one of the most aggressive fungal pathogens of Quercus species and is involved in the decline of Mediterranean cork oak forests and Californian oaks. Information regarding variation in virulence between strains is scarce. We hypothesize that D. corticola strains differ in virulence and consequently induce different symptoms in infected plants. To test this, infection assays were carried out on Quercus suber half‐sib seedlings with seven strains of D. corticola. Visual symptoms of infection (external lesions, leaf wilting, exudation and others) were recorded in parallel with physiological and biochemical parameters. All strains were able to cause lesions but at differing levels of aggressiveness. We show that internal lesion length did not correlate directly with strain aggressiveness and this agrees with physiological parameters that should be taken into account to infer about strain pathogenicity. Infection by all strains induced an overall negative impact on the net photosynthetic rate and an increase in the oxidative stress status of plants; however, significant differences were found when the effects of different strains were compared. Results also suggest that being under optimum growth conditions, prior to and during infection, allowed plants to respond to the pathogen. At the end of the experiment, some strains of D. corticola established a latent pathogen‐like relationship with cork oak. This is the first study to show that D. corticola virulence is strain‐dependent.
Expression and function of the metabotropic purinergic P2Y receptor family in experimental seizure models and patients with drug‐refractory epilepsy
Authors: Alves Mariana , Gomez‐Villafuertes Rosa , Delanty Norman , Farrell Michael A. , O'Brien Donncha F. , Miras‐Portugal Maria Teresa , Hernandez Miguel Diaz , Henshall David C. , Engel Tobias
Published: July 2017

Objective

ATP is released into the extracellular space during pathologic processes including increased neuronal firing. Once released, ATP acts on P2 receptors including ionotropic P2X and metabotropic P2Y receptors, resulting in changes to glial function and neuronal network excitability. Evidence suggests an involvement of P2Y receptors in the pathogenesis of epilepsy, but there has been no systematic effort to characterize the expression and function of the P2Y receptor family during seizures and in experimental and human epilepsy.

Methods

Status epilepticus was induced using either intra‐amygdala kainic acid or pilocarpine to characterize the acute‐ and long‐term changes in hippocampal P2Y expression. P2Y expression was also investigated in brain tissue from patients with temporal lobe epilepsy. Finally, we analyzed the effects of two specific P2Y agonists, ADP and UTP, on seizure severity and seizure‐induced cell death.

Results

Both intra‐amygdala kainic acid and pilocarpine‐induced status epilepticus increased the transcription of the uracil‐sensitive P2Y receptors P2ry2, P2ry4, and P2ry6 and decreased the transcription of the adenine‐sensitive P2Y receptors P2ry1, P2ry12, P2ry13. Protein levels of P2Y1, P2Y2, P2Y4, and P2Y6 were increased after status epilepticus, whereas P2Y12 expression was decreased. In the chronic phase, P2ry1, P2ry2, and P2ry6 transcription and P2Y1, P2Y2, and P2Y12 protein levels were increased with no changes for the other P2Y receptors. In hippocampal samples from patients with temporal lobe epilepsy, P2Y1 and P2Y2 protein expression was increased, whereas P2Y13 levels were lower. Demonstrating a functional contribution of P2Y receptors to seizures, central injection of ADP exacerbated seizure severity, whereas treatment with UTP decreased seizure severity during status epilepticus in mice.

Significance

The present study is the first to establish the specific hippocampal expression profile and function of the P2Y receptor family after experimental status epilepticus and in human temporal lobe epilepsy and offers potential new targets for seizure control and disease modification.
Comparison of preferences of healthcare professionals and MS patients for attributes of disease‐modifying drugs: A best‐worst scaling
Authors: Kremer Ingrid E. H. , Evers Silvia M. A. A. , Jongen Peter J. , Hiligsmann Mickaël
Published: July 2017

Background

The choice between disease‐modifying drugs (DMDs) for the treatment of multiple sclerosis (MS) becomes more often a shared decision between the patient and the neurologist and MS nurse. This study aimed to assess which DMD attributes are most important for the healthcare professionals in selecting a DMD for a patient. Subsequently, within this perspective, the neurologists’ and nurses’ perspectives were compared. Lastly, the healthcare professionals’ perspective was compared with the patients’ perspective to detect any differences that may need attention in the communication about DMDs.

Design

A best‐worst scaling (BWS) was conducted among 27 neurologists and 33 MS nurses treating patients with MS to determine the importance of 27 DMD attributes. These attributes were identified through three focus groups with MS patients in a previous study (N=19). Relative importance scores (RISs) were estimated for each attribute. Multivariable linear regression analyses were used to compare the different perspectives.

Results

According to the neurologists and nurses, safety of the DMD was the most important DMD attribute in the treatment decision, closely followed by effect on disability progression, quality of life and relapse rate. Patients with MS agreed with the importance of the last three attributes, but valued safety significantly lower (b=−2.59, P<.001).

Conclusions

This study suggests that, overall, neurologists and nurses regard the same DMD attributes as important as MS patients with the notable exception of safety. This study provides valuable information for the development of interventions to support shared decision making and highlights which attributes of DMDs may need additional attention.
Microstructure and phase evolution of Indian magnesite‐derived MgAl2O4 as a function of stoichiometry and ZrO2 doping
Authors: Mandal Somnath , Mondal Santanu , Das Kaberi
Published: July 2017

To aid development of cost‐effective sintered spinel as a refractory raw material, this paper presents an extensive analysis of microstructure and complex phase evolution of Al‐rich, Mg‐rich, and stoichiometric spinel aggregates derived from Indian magnesite and calcined alumina. Pore morphology in Al‐rich spinel was transformed upon sintering at 1650°C and corundum laths embedded in porous Al‐rich spinel matrix was formed. Stoichiometric spinel sintered at 1600°C consisted of mostly direct bonded angular equiaxed spinel grains which incorporated the impurities in solid solution. Mg‐rich spinel was composed of spinel grains with reduced angularity along with intergranular amorphous phase, small round monticellite grains, and periclase. EDS line scan revealed impurity‐free joins existed between direct bonded spinel grains. Mg‐rich spinel containing 0.65 wt% ZrO2 formed cubic ZrO2‐CaO‐MgO solid solution located along spinel boundaries, which reduced both intergranular amorphous phase and monticellite. This increased SiO2 and MgO content in spinel solid solution triggering exsolution of metastable cubic forsterite manifested as split spinel peaks in XRD pattern. A 14.7% reduction in slag penetration was exhibited upon doping Mg‐rich spinel with 0.21% ZrO2. Stoichiometric and Mg‐rich spinels attained 0.35% and 0.54% apparent porosity at 1600°C, which is better than most commercial sintered refractory spinels.
Successful treatment of metastatic clear cell carcinoma with nivolumab in a patient receiving dialysis treatment
Authors: Tabei Tadashi , Natsume Ichiro , Kobayashi Kazuki
Published: July 2017

The efficacy and safety of nivolumab for patients receiving dialysis treatment has not been established yet. Herein, we describe a patient on dialysis successfully treated with nivolumab as seventh‐line therapy for metastatic renal cell carcinoma. Before initiating nivolumab, he had respiratory discomfort induced by a lesion occluding the left intermediate bronchus that originated from the metastatic lymph node behind the tracheal bifurcation. Four weeks after nivolumab was initiated, his symptom remarkably improved, and the occlusion disappeared according to the bronchoscopy examination. The effectiveness and safety of nivolumab has continued for 6 months. There are few cases in which nivolumab has been given to patients on dialysis. In the present case, nivolumab was given to a patient on dialysis, and it resulted in a remarkable improvement without any adverse events.
Equal Opportunity and the Family: Levelling Up the Brighouse‐Swift Thesis
Authors: Engster Daniel
Published: July 2017

Although liberal political philosophers have long recognised the tension between equal opportunity and the family, most have assumed there is little society can do to mitigate it. Brighouse and Swift argue, by contrast, that an analysis of the value of the family reveals limits on the rights of parents to benefit their children and hence points to a way to reconcile the family with equal opportunity. Their solution for resolving the tension between equal opportunity and the family, however, leads to some untenable conclusions. A better solution for promoting equal opportunity in the family is to level up the opportunities that less advantaged parents have to promote the development and wellbeing of their children so that they are on par with the opportunities of the most advantaged parents. Five strategies are outlined for achieving this goal. Once society has provided all parents with real opportunities to fulfil their fiduciary duties, Brighouse and Swift's argument for limited parental partiality can be applied without contradiction. The result is an alternate solution for mitigating the conflict between equal opportunity and the family in liberal political philosophy.
Natural history of periodontitis: Disease progression and tooth loss over 40 years
Authors: Ramseier Christoph A. , Anerud Age , Dulac Mary , Lulic Martina , Cullinan Mary P. , Seymour Gregory J. , Faddy Malcolm J. , Bürgin Walter , Schätzle Marc , Lang Niklaus P.
Published: July 2017

Objectives

To assess long‐term attachment and periodontitis‐related tooth loss (PTL) in untreated periodontal disease over 40 years.

Material and Methods

Data originated from the natural history of periodontitis study in Sri Lankan tea labourers first examined in 1970. In 2010, 75 subjects (15.6%) of the original cohort were re‐examined.

Results

PTL over 40 years varied between 0 and 28 teeth (mean 13.1). Four subjects presented with no PTL, while 12 were edentulous. Logistic regression revealed attachment loss as a statistically significant covariate for PTL (p < .004). Markov chain analysis showed that smoking and calculus were associated with disease initiation and that calculus, plaque, and gingivitis were associated with loss of attachment and progression to advanced disease. Mean attachment loss <1.81 mm at the age of 30 yielded highest sensitivity and specificity (0.71) to allocate subjects into a cohort with a dentition of at least 20 teeth at 60 years of age.

Conclusions

These results highlight the importance of treating early periodontitis along with smoking cessation, in those under 30 years of age. They further show that calculus removal, plaque control, and the control of gingivitis are essential in preventing disease progression, further loss of attachment and ultimately tooth loss.
Evaluation of a technique for color correction in restoring anterior teeth
Authors: Rauber Gabrielle Branco , Bernardon Jussara Karina , Vieira Luiz Clovis Cardoso , Baratieri Luiz Narciso
Published: July 2017

Objective

This study aimed to evaluate the ability of the proposed technique in producing restorations that exhibit mimesis with tooth structure and to define a restorative clinical protocol.

Materials and Methods

For this study a typodont was used. The right upper central incisor with Class IV lesion was restored with the layering technique (reference tooth, RT). For the left upper central incisor with Class IV lesion, six teeth were restored monochromatically (test teeth, TT), using DA3.5 (n = 3) and DA4 (n = 3) composite resins—resulting in six unsatisfactory color restorations. TT were divided into six groups depending on the color of unsatisfactory restoration and preparation depth. First, a preparation was realized on the labial surface with 0.5 mm, 0.7 mm or 1.0 mm of depth. A second preparation was then performed to reproduce the dentinal mamelons. Next, adhesive procedures were performed and the teeth restored. Opaque halo, opalescent halo and vestibular enamel were then reproduced by the addition of different composite resins. The RT and TT were photographed side by side in typodont to obtain six photographic prints. The photographs of the groups were subjected to visual evaluation by 120 volunteers via a questionnaire. Data were analyzed by the prevalence of answers, and Chi‐square test was used to investigate the association between variables at .05 significance. Furthermore, ΔE of groups was evaluated in comparison RT.

Results

The results demonstrated that the moderate intensity restorations (DA3.5) with depths of 0.5 mm and 0.7 mm had the highest prevalence of acceptance. For severe intensity restorations (DA4), the preparation depth of 1.0 mm obtained better acceptance.

Conclusions

The technique was able to modify the final color of Class IV restorations, producing satisfactory color restorations.

CLINICAL SIGNIFICANCE

This technique can be used for color correction in cases of Class IV restorations, in situations where there is no time for immediate layered restoration, and as a restorative technique.
Whitening‐dependent changes of fluorescence of extracted human teeth
Authors: Pereira Sanchez Natalie , Aleksic Aleksandar , Dramicanin Miroslav , Paravina Rade D.
Published: July 2017

Objective

To evaluate in vitro the fluorescence properties of extracted human teeth whitened with 40% hydrogen peroxide.

Materials and Methods

A total of 28 extracted human teeth were pumiced for 1 minute using a low‐speed dental handpiece and a disposable rubber cup. Pre‐whitening fluorescence measurements (T0), maximum excitation (Exmax), maximum emission (Emmax), and maximum intensity (Imax108), were performed using a spectrofluorometer. After T0 measurements, the teeth were whitened using the in‐office method with 40% hydrogen peroxide, three times for 20 minutes. The fluorescence parameters were measured under the same conditions 7 and 14 days after bleaching (T1 and T2, respectively).

Results

Exmax exhibited a broader range 7 days after whitening and decreased after 14 days. The Emmax and Imax108 displayed a narrower range after whitening. The mean Exmax differed significantly between the time points (F = 20.09. P < .001). The corresponding analysis for the mean Emmax differed significantly between the time points (F = 16.69, P < .001). The same was true for the mean Imax108 (F = 9.69, P < .001).

Conclusions

Within the limitations of this study, whitening provoked statistically significant changes in fluorescence of the intact teeth in vitro.

Clinical significance

The appearance of human teeth and dental materials and their changes upon aging and exposure to different agents (staining, whitening) is a topic of great relevance to esthetic dentistry. While some appearance parameters, such as color, translucency, and gloss, have been thoroughly studied, fluorescence and its influence on overall tooth appearance is still not well understood, yet it has influenced the development of fluorescence emitting restorative materials.
Effectiveness of Light Therapy in Cognitively Impaired Persons: A Metaanalysis of Randomized Controlled Trials
Authors: Chiu Huei‐Ling , Chan Pi‐Tuan , Chu Hsin , Hsiao Shu‐Tai Sheen , Liu Doresses , Lin Chueh‐Ho , Chou Kuei‐Ru
Published: July 2017

Objectives

To explore the effects of light therapy on behavioral disturbances (BDs), sleep quality, and depression.

Design

Meta‐analysis of randomized controlled trials.

Setting

PubMed, Cochrane Library, Medline, EMBASE, Web of Science, and clinicaltrials.gov of selected randomized controlled trials and previous systematic reviews were searched.

Participants

Cognitively impaired persons.

Measurements

Information was extracted on study characteristics, quality assessment, and outcomes. Outcome measures included BDs, sleep quality, and depression.

Results

Nine randomized controlled trials were examined. The results showed that light therapy has a moderate effect on BD (g = −0.61) and depression (g = −0.58) and a small effect on total sleep time at night (g = 0.25). Subgroup analysis indicated that a light intensity of 2,500 lux or greater has a greater effect on depression than an intensity of less than 2,500 lux (P = .03), and the low risk of bias in blinding was superior to the RCTs deemed to be of high or unclear risk of bias in blinding in terms of BD (P = .02).

Conclusion

Light therapy can relieve BD, improve sleep quality, and alleviate symptoms of depression for cognitively impaired persons.
Dementia risk and prevention by targeting modifiable vascular risk factors
Authors: Tariq Sana , Barber Philip A.
Published: July 2017

The incidence of dementia is expected to double in the next 20 years and will contribute to heavy social and economic burden. Dementia is caused by neuronal loss that leads to brain atrophy years before symptoms manifest. Currently, no cure exists and extensive efforts are being made to mitigate cognitive impairment in late life in order to reduce the burden on patients, caregivers, and society. The most common type of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) often co‐exists in the brain and shares common, modifiable risk factors, which are targeted in numerous secondary prevention trials. There is a growing need for non‐pharmacological interventions and infrastructural support from governments to encourage psychosocial and behavioral interventions. Secondary prevention trials need to be redesigned based on the risk profile of individual subjects, which require the use of validated and standardized clinical, biological, and neuroimaging biomarkers. Multi‐domain approaches have been proposed in high‐risk populations that target optimal treatment; clinical trials need to recruit individuals at the highest risk of dementia before symptoms develop, thereby identifying an enriched disease group to test preventative and disease modifying strategies. The underlying aim should be to reduce microscopic brain tissue loss by modifying vascular and lifestyle risk factors over a relatively short period of time, thus optimizing the opportunity for preventing dementia in the future. Collaboration between international research groups is of key importance to the optimal use and allocation of existing resources, and the development of new techniques in preventing dementia.

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This article is part of the Special Issue “Vascular Dementia”.
Inpatient palliative care referral and 9‐month hospital readmission in patients with congestive heart failure: a linked nationwide analysis
Authors: Wiskar K. , Celi L. A. , Walley K. R. , Fruhstorfer C. , Rush B.
Published: July 2017

Objective

End‐stage heart failure (HF) is characterized by high symptom burden and frequent hospitalization. Palliative care (PC) is recommended for advanced HF, and there is some evidence in other diseases that this may reduce readmission rates. We attempted examine the association of an inpatient PC visit on hospital readmission for patients admitted with HF.

Methods

Retrospective linked nationwide analysis from 2013 with 9‐month follow‐up for all hospital readmissions for patients admitted with HF exacerbations using the Nationwide Readmission Database (NRD). The NRD gathers all hospital admissions for patients from 22 states and tracks patients throughout the year, allowing for examination of readmission statistics. A propensity score model for PC visit was made, and patients were matched in a 1 : 1 fashion.

Results

There were 102 746 patients who survived an admission for HF in the first 3 months of 2013. Of these, 2287 (2.2%) patients had a PC visit as inpatients.

After matching based on propensity for a PC visit during the index hospitalization, 2282 patients who received a PC visit were matched to 2282 patients who did not. Those receiving a PC visit were less likely to be readmitted for HF (9.3% vs. 22.4%, P < 0.01) or for any cause (29.0% vs. 63.2%, P < 0.01) during the 9‐month follow‐up period. The average hospital charges during the follow‐up period for the non‐PC cohort were $77 643 per patient. The average charges for PC patients were $23 200 (P < 0.01).

Conclusions

Patients with HF who received an inpatient PC visit had significantly lower rates of all‐cause and HF‐specific readmission in the subsequent 9 months. Total 9‐month hospital charges were also significantly lower for patients who received an inpatient PC visit.