bluuebunny/crossref_metadata_2025 huggingface dataset:
Leptin and the vasculature in young adults: The African‐PREDICT study
Authors: Ahiante Blessing O. , Smith Wayne , Lammertyn Leandi , Schutte Aletta E.
Published: October 2018

Background and aim

Information regarding the effect of leptin on the vasculature in young healthy adults at risk for cardiovascular disease development is limited. We therefore examined the associations between measures of subclinical atherosclerosis (carotid intima‐media thickness, carotid cross‐sectional wall area), large artery stiffness (pulse wave velocity) and a measure of endothelial dysfunction (von Willebrand factor [vWF]) with leptin in young healthy men and women.

Methods

In a cross‐sectional study in South Africa involving 820 normotensive individuals (337 men and 483 women) aged 20‐30 years, we measured carotid intima‐media thickness, carotid cross‐sectional wall area, pulse wave velocity, vWF from citrated plasma and leptin from serum.

Results

Despite sevenfold higher leptin in women than men (P < 0.001), only in young healthy men, we observed negative, independent associations between measures of carotid wall thickness (carotid intima‐media thickness: R2 = 0.05; β = −0.20; P = 0.036; carotid cross‐sectional wall area: R2 = 0.05; β = −0.20; P = 0.035) with leptin in multivariable‐adjusted regression analyses. When reviewing these associations across body mass index categories, we found an association to be evident only in overweight men (carotid intima‐media thickness: R2 = 0.15; β = −0.41; P = 0.007; carotid cross‐sectional wall area: R2 = 0.21; β = −0.47; P = 0.002). No association was observed in the women or between pulse wave velocity and vWF with leptin.

Conclusion

In young healthy men, we found a beneficial inverse association between measures of carotid wall thickness and circulating leptin, thereby supporting a potential vascular protective role of leptin.
Phase I study of domatinostat (4SC‐202), a class I histone deacetylase inhibitor in patients with advanced hematological malignancies
Authors: von Tresckow Bastian , Sayehli Cyrus , Aulitzky Walter E. , Goebeler Maria‐Elisabeth , Schwab Matthias , Braz Eunice , Krauss Babett , Krauss Rolf , Hermann Frank , Bartz René , Engert Andreas
Published: October 2018

Objectives

Domatinostat (4SC‐202) is a selective class I histone deacetylase inhibitor (HDACi). This phase I study investigated safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and antitumor activity in patients with advanced hematological malignancies.

Methods

Domatinostat was administered orally once (QD) or twice daily (BID) on days 1‐14 with 7 days off or continuously days 1‐21 in a 3 + 3 design at 7 dose levels from 25 to 400 mg total daily dose (TDD). Twenty‐four patients were treated with domatinostat.

Results

No formal maximum tolerated dose (MTD) was determined. One dose‐limiting toxicity (DLT, grade 4 hypercalcemia) occurred during 200 mg BID continuous treatment. Six patients were reported with ≥ grade 3 treatment‐related adverse events (TRAE; grade 3 hematological in three patients, grade 3 and grade 4 liver enzyme increase in 2 patients, grade 4 pulmonary embolism, and grade 4 hypercalcemia in one patient each). Higher grade hepatic TRAE occurred in the 200 mg BID continuous treatment cohort. Out of 24 patients, 1 achieved a complete response, 1 achieved a partial response, and 18 had stable disease as best response.

Conclusion

Administration of domatinostat was safe, well tolerated with signs of antitumor activity. Four hundred milligram TDD in a 200 mg BID schedule (14 + 7) is the recommended phase II dose for monotherapy.
Synchrony surfacing: Epicortical recording of correlated action potentials
Authors: Bockhorst Tobias , Pieper Florian , Engler Gerhard , Stieglitz Thomas , Galindo‐Leon Edgar , Engel Andreas K.
Published: October 2018

Synchronous spiking of multiple neurons is a key phenomenon in normal brain function and pathologies. Recently, approaches to record spikes from the intact cortical surface using small high‐density arrays of microelectrodes have been reported. It remained unaddressed how epicortical spiking relates to intracortical unit activity. We introduced a mesoscale approach using an array of 64 electrodes with intermediate diameter (250 μm) and combined large‐coverage epicortical recordings in ferrets with intracortical recordings via laminar probes. Empirical data and modelling strongly suggest that our epicortical electrodes selectively captured synchronized spiking of neurons in the cortex beneath. As a result, responses to sensory stimulation were more robust and less noisy compared to intracortical activity, and receptive field properties were well preserved in epicortical recordings. This should promote insights into assembly‐coding beyond the informative value of subdural EEG or single‐unit spiking, and be advantageous to real‐time applications in brain‐machine interfacing.
Waist‐to‐hip ratio affects female body attractiveness and modulates early brain responses
Authors: Del Zotto Marzia , Framorando David , Pegna Alan J.
Published: October 2018

This investigation examined the electrophysiological response underlying the visual processing of waist‐to‐hip ratio (WHR) in female bodies, a characteristic known to affect perceived attractiveness. WHRs of female bodies were artificially adjusted to values of 0.6, 0.7, 0.8 or 0.9. Behavioural ratings of attractiveness of the bodies revealed a preference for WHRs of 0.7 in the overall group of participants, which included both male and female heterosexual individuals. Event‐related potentials (ERPs) were then recorded while participants performed a selective attention task involving photographs of female models and scrambled images. Results showed that the P1 (80–120 ms) and N1 (130–170 ms) components situated over posterior brain regions were the earliest components to be modulated by attention and bodies. Interestingly, the vertex‐positive potential, occurring between 120–180 ms, produced a greater positivity for WHRs of 0.7 compared to the other ratios. However, this increase was only observed when the body stimuli were attended, while no effect was observed for unattended bodies. These findings provide evidence of an early brain sensitivity to visual attributes that constitute secondary sexual characteristics. Although they are relatively discrete from the point of view of their physical quality, these signs possess strong behavioural significance, producing greater reported attractiveness, likely by conveying the biological meaning that signals good health and greater reproductive success. Our results therefore reveal that attributes associated with sexual attractiveness in female bodies are processed rapidly in the stream of visual processing.
Theiler's disease associated with administration of tetanus antitoxin contaminated with nonprimate (equine) hepacivirus and equine parvovirus‐hepatitis virus
Authors: Kopper J. J. , Schott H. C. , Divers T. J. , Mullaney T. , Huang L. , Noland E. , Smedley R.
Published: October 2018

An 11‐year‐old Trakehner gelding was presented for evaluation of lethargy, decreased appetite, mild icterus, and elevated hepatic enzyme activities. Physical examination, serum chemistry results, and liver biopsy histopathologic findings were supportive of Theiler's disease. Polymerase chain reaction (PCR) testing results of serum and liver tissue were positive for nonprimate (equine) hepacivirus (NPHV) and a novel equine parvovirus‐hepatitis virus (EqPV‐H).PCRtesting of the lot of tetanus antitoxin administered to the gelding 3 months previously also yielded positive results forNPHVand EqPV‐H. Treatment included supportive care and clinical signs resolved within 1 week, although hepatic enzyme activities remained elevated for several months. The horse successfully returned to work as a hunter/jumper for about 1 year until it developed a forelimb lameness and progressive atrophy of shoulder musculature (sweeney), prompting a decision for euthanasia 20 months after initial evaluation. SerialPCRtesting of serum revealed persistent infection with bothNPHVand EqPV‐H and necropsy examination revealed chronic active hepatitis, mild liver atrophy, and positivePCRresults forNPHVand EqPV‐H in liver tissue. This case highlights the possible risk of administering potentially contaminated biologics of equine origin and the importance of screening for recently identified hepatic viruses in donors from which blood products are prepared.
The Equality Principle: Splitting the Difference in Custody Disputes
Authors: Ngaosuvan Leonard S.
Published: October 2018

In some custody disputes parents are equally fit, other factors are not decisive, shared custody is ruled out, and the parental conflict is the only threat to children's well‐being. There are no systematic principles to resolve these disputes. To fill this gap, I introduce the equality principle. Following splitting the difference and goal‐setting theory, parents renegotiate under threat of randomization. If renegotiation fails, their chances of winning are equal. This principle may improve children's well‐being, parental behavior, court efficiency, and custody investigations. The principle is discussed in terms of child perspective, appellate rights, applicability, irrationality, and attorney effects on negotiations.
Keeping the Dream Alive: Deferred Action for Childhood Arrivals and the Necessary Next Step
Authors: Bogart Kelly
Published: October 2018

In September 2017, the Trump administration announced it was repealing the executive memorandum that provided Deferred Action for Childhood Arrivals (DACA). Rescinding DACA revokes protections promised to hundreds of thousands of people brought to the United States as children who now reside in the United States without immigration status. This Note proposes that because both DACA's implementation and its repeal were constitutional, Congress must act to prevent those protected by the DACA program from having their previous trust in the U.S. government now used against them.
Parental Mental Illness: The Importance of Requiring Parental Mental Health Evaluations in Child Custody Disputes
Authors: Jutchenko Ashley R.
Published: October 2018

Parental mental illness is a challenging issue in child custody disputes. Mentally ill parents engaged in custody battles with former partners can be concerning for a court that must determine what is in the best interests of the child. Parental mental health is critical in custody determinations, yet New York does not require a mental health evaluation for mentally ill parents. This Note proposes that the New York legislature amend Domestic Relations Law Section 240 to require mental health evaluations for mentally ill parents when deciding what is in the best interests of the child.
Extreme drought pushes stream invertebrate communities over functional thresholds
Authors: Aspin Thomas W. H. , Khamis Kieran , Matthews Thomas J. , Milner Alexander M. , O’Callaghan Matthew J. , Trimmer Mark , Woodward Guy , Ledger Mark E.
Published: October 2018

Functional traits are increasingly being used to predict extinction risks and range shifts under long‐term climate change scenarios, but have rarely been used to study vulnerability to extreme climatic events, such as supraseasonal droughts. In streams, drought intensification can cross thresholds of habitat loss, where marginal changes in environmental conditions trigger disproportionate biotic responses. However, these thresholds have been studied only from a structural perspective, and the existence of functional nonlinearity remains unknown. We explored trends in invertebrate community functional traits along a gradient of drought intensity, simulated over 18 months, using mesocosms analogous to lowland headwater streams. We modelled the responses of 16 traits based on a priori predictions of trait filtering by drought, and also examined the responses of trait profile groups (TPGs) identified via hierarchical cluster analysis. As responses to drought intensification were both linear and nonlinear, generalized additive models (GAMs) were chosen to model response curves, with the slopes of fitted splines used to detect functional thresholds during drought. Drought triggered significant responses in 12 (75%) of the a priori‐selected traits. Behavioural traits describing movement (dispersal, locomotion) and diet were sensitive to moderate‐intensity drought, as channels fragmented into isolated pools. By comparison, morphological and physiological traits showed little response until surface water was lost, at which point we observed sudden shifts in body size, respiration mode and thermal tolerance. Responses varied widely among TPGs, ranging from population collapses of non‐aerial dispersers as channels fragmented to irruptions of small, eurythermic dietary generalists upon extreme dewatering. Our study demonstrates for the first time that relatively small changes in drought intensity can trigger disproportionately large functional shifts in stream communities, suggesting that traits‐based approaches could be particularly useful for diagnosing catastrophic ecological responses to global change.
MicroRNA‐342 inhibits tumor growth via targeting chemokine CXCL12 involved in macrophages recruitment/activation
Authors: Tian Yijun , Matsui Sayaka , Touma Maki , Wu Qiong , Sugimoto Kenkichi
Published: October 2018

MicroRNAs (miRNAs) play important roles in initiation, development, progression and metastasis of tumors. MiR‐342 has been reported as a tumor suppressor or an onco‐miRNA based on functions or expression changes in various types of cancers. However, the biological roles and underlying molecular mechanisms of miR‐342 in tumorigenesis remain largely unknown. Here, we found that miR‐342 was expressed significantly less in a murine MS‐K tumor cell line that showed riched blood vessels. Over‐expression of miR‐342 in MS‐K cells inhibited cell proliferation, colony formation, reduced frequency of S phase population in vitro and suppressed tumor growth in vivo. Moreover, increasing miR‐342 impeded blood vessels formation and accumulation of macrophages (CD11b+) in tumors. By bioinformatic analysis and dual‐luciferase reporter assays, chemokine CXCL12 was identified as a direct target of miR‐342. Restored Cxcl12 expression in MS‐K‐miR‐342 cells could rescue cell proliferation in vitro. In MS‐K‐miR‐342 tumor‐infiltrated macrophages, expression of proangiogenic genes (Vegf‐A and Thbs1) and M2‐subtype macrophage markers (Cd163, Dectin1 and Ym1) was significantly down‐regulated compared with controls. Moreover, lower level of Cxcl12 and its receptor Cxcr4 was observed in the macrophages of MS‐K‐miR‐342 tumors, and MS‐K‐miR‐342 derived miR‐342, but not endogenous miR‐342, might contribute to Cxcl12 suppression in TAM. These results suggest that miR‐342 is involved in MS‐K tumor growth as a tumor suppressor by targeting chemokine CXCL12.
“Change is what can actually make the tough times better”: A patient‐centred patient safety intervention delivered in collaboration with hospital volunteers
Authors: Louch Gemma , Mohammed Mohammed A. , Hughes Lesley , O'Hara Jane
Published: October 2018

Background

The PRASE (Patient Reporting and Action for a Safe Environment) intervention provides a way to systematically collect patient feedback to support service improvement. To provide a sustainable mechanism for the PRASE intervention, a 2‐year improvement project explored the potential for hospital volunteers to facilitate the collection of PRASE feedback.

Objective

To explore the implementation of the PRASE intervention delivered in collaboration with hospital volunteers from the perspectives of key stakeholders.

Design

A qualitative case study design was utilized across three acute NHS trusts in the United Kingdom between March 2016 and October 2016. Ward level data (staff interviews; action planning meeting recordings; implementation fidelity information) were analysed taking a pen portrait approach. We also carried out focus groups with hospital volunteers and interviews with voluntary services/patient experience staff, which were analysed thematically.

Results

Whilst most ward staff reported feeling engaged with the intervention, there were discordant views on its use and usefulness. The hospital volunteers were positive about their involvement, and on some wards, worked with staff to produce actions to improve services. The voluntary services/patient experience staff participants emphasised the need for PRASE to sit within an organisations’ wider governance structure.

Conclusion

From the perspective of key stakeholders, hospital volunteers facilitating the collection of PRASE feedback is a feasible means of implementing the PRASE intervention. However, the variability around ward staff being able to use the feedback to make changes to services demonstrates that it is this latter part of the PRASE intervention cycle that is more problematic.
Endometrial hyperplasia and the risk of coexistent cancer: WHO versus EIN criteria
Authors: Travaglino Antonio , Raffone Antonio , Saccone Gabriele , Mollo Antonio , De Placido Giuseppe , Insabato Luigi , Zullo Fulvio
Published: October 2018

Endometrial hyperplasia (EH) is classified into benign and precancerous according to two different histomorphological systems: the World Health Organisation (WHO) system (based on the subjective evaluation of cytological atypia) and the endometrial intraepithelial neoplasia (EIN) system (based on a combination of several parameters that are assessable subjectively, or objectively through computerised analysis). The American College of Obstetricians and Gynecologists recommends use of the EIN system. Nonetheless, a higher prognostic value for EIN criteria was demonstrated only with the objective assessment, which is not routinely applicable. The aim of this study was to evaluate which of the subjective classifications of EH (WHO or EIN) has better prognostic value, by assessing the risk of coexistent cancer. Electronic databases were searched for relevant articles from the inception of the databases to July 2018. All studies assessing the presence of cancer on hysterectomy specimens after a preoperative histological diagnosis of EH were included. Odds ratios (ORs), sensitivity and specificity were calculated with 95% confidence intervals (CIs). Sixteen cohort studies and three case–control studies, assessing 2582 EHs, were included. The WHO criteria showed an OR of 11.15 (95% CI 7.65–16.24), a sensitivity of 0.86 (95% CI 0.82–0.90) and a specificity of 0.67 (95% CI 0.64–0.70) for coexistent cancer. The subjective EIN system showed a similar OR (11.85, 95% CI 4.91–28.62; P = 0.90), higher sensitivity (0.98, 95% CI 0.94–0.99), and lower specificity (0.29, 95% CI 0.24–0.34). The WHO system and the subjective EIN system have similar prognostic values. However, the EIN criteria appear to be more sensitive and thus more suitable for selecting women who need to be treated, whereas the WHO criteria, based on cytological atypia, seem to be more specific for lesions at higher risk of cancer. Therefore, integration of the EIN system with cytological atypia should be considered.
Contrasting strategies for wing‐moult and pre‐migratory fuelling in western and eastern populations of Common Whitethroat Sylvia communis
Authors: Remisiewicz Magdalena , Bernitz Zephné , Bernitz Herman , Burman Marc S. , Raijmakers Jacobus M.H. , Raijmakers Johannes H.F.A. , Underhill Les G. , Rostkowska Anna , Barshep Yahkat , Soloviev Sergej A. , Siwek Ilona
Published: October 2018

Trade‐offs between moult and fuelling in migrant birds vary with migration distance and the environmental conditions they encounter. We compared wing moult and fuelling at the northern and southern ends of migration in two populations of adult Common Whitethroats Sylvia communis. The western population moults most remiges at the breeding grounds in Europe (e.g. Poland) and migrates 4000–5000 km to western Africa (e.g. Nigeria). The eastern population moults all remiges at the non‐breeding grounds and migrates 7000–10 000 km from western Asia (e.g. southwestern Siberia) to eastern and southern Africa. We tested the hypotheses that: (1) Whitethroats moult their wing feathers slowly in South Africa, where they face fewer time constraints than in Poland, and (2) fuelling is slower when it coincides with moulting (Poland, South Africa) than when it occurs alone (Siberia, Nigeria). We estimated moult timing of primaries, secondaries and tertials from moult records of Polish and South African Whitethroats ringed in 1987–2017 and determined fuelling patterns from the body mass of Whitethroats ringed in all four regions. The western population moulted wing feathers in Poland over 55 days (2 July–26 August) at a varying rate, up to 13 feathers simultaneously, but fuelled slowly until departure in August–mid‐September. In Nigeria, during the drier period of mid‐February–March they fuelled slowly, but the fuelling rate increased three‐fold in April–May after the rains before mid‐April–May departure. The eastern population did not moult in Siberia but fuelled three times faster before mid‐July–early August departure than did the western birds moulting in Poland. In South Africa, the Whitethroats moulted over 57 days (2 January–28 February) at a constant rate of up to nine feathers simultaneously and fuelled slowly from mid‐December until mid‐April–May departure. These results suggest the two populations use contrasting strategies to capitalize on food supplies before departure from breeding and non‐breeding grounds.
Central–periphery gradient of individual quality within a colony of Black‐headed Gulls
Authors: Indykiewicz Piotr , Podlaszczuk Patrycja , Kamiński Maciej , Włodarczyk Radosław , Minias Piotr
Published: October 2018

Central nesting sites within avian colonies are often more profitable in terms of fitness, as they can offer better protection against predators compared with colony edges. Thus, central sites are expected to attract high‐quality individuals, which should produce a clear central–periphery gradient in the phenotypic quality of nesting individuals and reproductive output within colonies. The aim of this study was to assess spatial patterns of individual quality within a colony of a common larid, the Black‐headed GullChroicocephalus ridibundus. We found that laying was advanced in the central zone of the colony when compared with the periphery, and central pairs tended to lay larger eggs and had higher hatching success than peripheral pairs. Centrally nesting individuals had higher blood haemoglobin concentrations, size‐corrected body mass and heterozygosity (males only), indicating their better condition and higher genetic quality. In contrast, central females had lower plasma albumin concentration, which could possibly be attributed to their greater investment in egg production. Finally, pairs breeding in the central zone of the colony had an elevated heterophil/lymphocyte ratio, suggesting that social stress can be recognized as an important cost of nesting in dense aggregations. The results provide empirical support for central–periphery gradients in the individual quality of colonially nesting Black‐headed Gulls, indicating that spatial gradients in pair quality should be carefully taken into account when conducting research on colonial birds.
In situ synthesis and thermal shock resistance of a cordierite‐mullite composite for solar thermal storage
Authors: Cheng Hao , Ye Fen , Chang Jun , Wu Sizhan
Published: October 2018

Cordierite‐mullite composite ceramic was synthesized in situ by semidry pressing and pressureless sintering from andalusite, kaolin, γ‐Al2O3, talc, potassium feldspar, and albite in air. The effects of composition and sintering temperature on the density, bending strength, thermal shock stability, crystal phases, and microstructure of the specimens were studied. The results show that specimen B2 (the theoretical content of cordierite was 20 wt%) has excellent performance, that is, a bending strength of 104.59 MPa, 30 cycles of thermal shock resistance without cracking, and a loss rate of 13.12%. X‐ray diffractometer (XRD) analysis and scanning electron microscope (SEM) micrographs showed that spherical cordierite crystals were grown on the surface of the mullite, therefore, the specimen possessed a superior bending strength and thermal shock resistance, where a great number of granules combined to restrain crack initiation as well as propagation over time during the thermal shock test. The thermal conductivity of specimen B2 was determined to be 3.83 W/(m·K) (36°C), and the sensible heat storage density was 1136 kJ/kg, with the temperature difference (ΔT) ranging from 0 to 800°C. Consequently, the cordierite‐mullite composite is a potentially applicable material for solar thermal storage.
Language, sexuality and inclusive pedagogy
Authors: Sauntson Helen
Published: October 2018

This paper examines linguistic practices of inclusion and exclusion relating to sexual orientation and sexual identity as they surface in the context of language education and multilingual contexts. I argue that queer linguistics can provide a helpful theoretical framework for examining how normative and non‐normative constructions of sexual identity are enacted inscribed in language practices in classrooms, and how these language practices may effect particular discourses of sexuality. I examine extracts of interview data with young people analysed usingappraisalanalysis. The analysis focuses on how language works as a form of social practice which can include and exclude sexual identities in classroom settings.
Estimate of the incidence of bladder cancer in Africa: A systematic review and Bayesian meta‐analysis
Authors: Adeloye Davies , Harhay Michael O , Ayepola Olayemi O , Dos Santos Jhonathan PR , David Rotimi A , Ogunlana Olubanke O , Gadanya Muktar , Osamor Victor C , Amuta Ann O , Iweala Emeka E , Auta Asa , Rebbeck Timothy R
Published: October 2018

Objectives

To quantify the epidemiology of bladder cancer in Africa to guide a targeted public health response and support research initiatives.

Methods

We systematically searched publicly available sources for population‐based registry studies reporting the incidence of bladder cancer in Africa between January 1980 and June 2017. Crude incidence rates of bladder cancer were extracted. A Bayesian network meta‐analysis model was used to estimate incidence rates.

Results

The search returned 1328 studies. A total of 22 studies carried out across 15 African countries met our pre‐defined selection criteria. Heterogeneity across studies was high (I2 = 98.9%, P < 0.001). The pooled incidence of bladder cancer in Africa was 7.0 (95% credible interval 5.8–8.3) per 100 000 population in men and 1.8 (95% credible interval 1.2–2.6) per 100 000 in women. The incidence of bladder cancer was consistently higher in North Africa in both sexes. Among men, we estimated a pooled incidence of 10.1 (95% credible interval 7.9–11.9) per 100 000 in North Africa and 5.0 (95% credible interval 3.8–6.6) per 100 000 in sub‐Saharan Africa. In women, the pooled incidence was 2.0 (95% credible interval 1.0–3.0) per 100 000 and 1.5 (95% credible interval 0.9–2.0) per 100 000 in North Africa and sub‐Saharan Africa, respectively. Incidence rates increased significantly among men from 5.6 (95% credible interval 4.2–7.2) in the 1990s to 8.5 (95% credible interval 6.9–10.1) per 100 000 in 2010.

Conclusions

The present study suggests a growing incidence of bladder cancer in Africa in recent years, particularly among men and in North Africa. This study also highlights the lack of quality data sources and collection of essential clinical and epidemiological data in several African countries, and this hinders public health planning.
Treatment patterns and outcomes in patients with unresectable or metastatic renal cell carcinoma in Japan
Authors: Harada Kenichi , Nozawa Masahiro , Uemura Motohide , Tatsugami Katsunori , Osawa Takahiro , Yamana Kazutoshi , Kimura Go , Fujisawa Masato , Nonomura Norio , Eto Masatoshi , Shinohara Nobuo , Tomita Yoshihiko , Kondo Yukihiro , Ochi Kenya , Anazawa Yoshio , Uemura Hirotsugu
Published: October 2018

Objectives

To clarify treatment patterns and outcomes for patients with unresectable or metastatic renal cell carcinoma in the molecular target therapy era in Japan.

Methods

A multicenter, retrospective medical chart review study was carried out. Patients diagnosed with unresectable or metastatic renal cell carcinoma between January 2012 and August 2015 were enrolled. Data extracted from medical records included treatment duration, grade ≥3 adverse events, reason for discontinuation for each targeted therapy and survival data until August 2016.

Results

Of 277 eligible patients, 266, 170 and 77 received first‐, second‐ and third‐line systemic treatment, respectively. Tyrosine kinase inhibitors were the most common first‐line therapy (72.2%), followed by mammalian target of rapamycin inhibitors (14.3%) and cytokines (13.5%). Among 170 patients who received second‐line treatment, tyrosine kinase inhibitor–tyrosine kinase inhibitor was the most common sequence (58.8%), followed by tyrosine kinase inhibitor–mammalian target of rapamycin inhibitor (14.1%) and cytokine–tyrosine kinase inhibitor (14.1%). With a median follow‐up period of 19.8 months, median overall survival was not reached at 48 months. Patients who discontinued first‐line tyrosine kinase inhibitors in <6 months showed poorer overall survival compared with patients who received first‐line tyrosine kinase inhibitors for ≥6 months.

Conclusions

The present analysis illustrates the contemporary treatment patterns and prognosis for patients with unresectable or metastatic renal cancer in a real‐world setting in Japan. Tyrosine kinase inhibitor–tyrosine kinase inhibitor represents the most commonly used sequence. Shorter treatment duration of first‐line tyrosine kinase inhibitors is associated with poorer prognosis, suggesting the need for better treatment options.
Maternal Postpartum Depression Increases Vulnerability for Toddler Behavior Problems through Infant Cortisol Reactivity
Authors: Lawler Jamie M. , Bocknek Erika L. , McGinnis Ellen W. , Martinez‐Torteya Cecilia , Rosenblum Katherine L. , Muzik Maria
Published: October 2018

The current study examined the role of hypothalamic‐pituitary‐adrenal reactivity (a physiological indicator of stress) in early infancy as a mediator of the relationship between maternal postpartum depression and toddler behavior problems. Participants were 137 at‐risk mothers and their children participating in a longitudinal study of intergenerational transmission of risk. Mothers’ depression was measured five times during the infants’ first 18 months. Infant cortisol was collected during a social stressor (the still‐face paradigm) when infants were 6 months old, and mothers reported on toddlers’ internalizing and externalizing symptoms at 18 months. Among this sample of high‐risk mother–infant dyads, early postpartum depression predicted atypical infant cortisol reactivity at 6 months, which mediated the effect of maternal depression on increased toddler behavior problems. Clinical implications are discussed.
A shared coevolutionary history does not alter the outcome of coalescence in experimental populations of Pseudomonas fluorescens
Authors: Castledine Meaghan , Buckling Angus , Padfield Daniel
Published: October 2018

Community coalescence, the mixing of multiple communities, is ubiquitous in natural microbial communities. During coalescence, theory suggests the success of a population will be enhanced by the presence of species it has coevolved with (relative to foreign species), because coevolution will result in greater resource specialization to minimize competition. Thus, more coevolved communities should dominate over less coevolved communities during coalescence events. We test these hypotheses using the bacterium Pseudomonas fluorescens which diversifies into coexisting niche‐specialist morphotypes. We first evolved replicate populations for ~40 generations and then isolated evolved genotypes. In a series of competition trials, we determined if using coevolved versus random genotypes affected the relative performance of “communities” of single and multiple genotypes. We found no effect of coevolutionary history on either genotype fitness or community performance, which suggests parallel (co)evolution between communities. However, fitness was enhanced by the presence of other genotypes of the same strain type (wild‐type or an isogenic strain with a LacZ marker; the inclusion of the latter necessary to distinguish genotypes during competition), indicative of local adaptation with respect to genetic background. Our results are the first to investigate the effect of (co)evolution on the outcome of coalescence and suggest that when input populations are functionally similar and added at equal mixing ratios, the outcome community may not be asymmetrically dominated by either input population.
Modern frontiers and applications of spray‐freeze‐drying in design of food and biological supplements
Authors: Dutta Sayantani , Moses J. A. , Anandharamakrishnan C.
Published: October 2018

Spray‐freeze‐drying (SFD) is a unique tandem technique combining spray drying (SD) and freeze drying (FD), and exploiting the advantages of both. SFD is particularly suitable for volatiles, biologicals, and food supplements that are sensitive to process extremities of temperature (SD) and time and cost (FD). Although SFD has been an area of interest to scientists for some time, there have been few very interesting investigations in food science in the recent past, which highlight the versatility and utility of this method, and been discussed in this review. The sources for SFD range from flavor ingredients to vegetables, lipids, enzymes, vitamins, and proteins. The extensive research findings in this domain have been collated in this focused review with the objective of providing the readers an essence of the forays made in this technology and the future possibilities it promises.

Practical applications

Spray‐freeze‐drying is suitable for volatiles, biologicals, and food supplements that are sensitive to process extremities of temperature (spray drying) and time and cost (freeze drying). Applications of SFD range from flavor ingredients to vegetables, lipids, enzymes, vitamins, and proteins. It offers reduced drying time, higher retention of bioactives postdrying, and improved rehydration, which makes it a method of choice. Considering the possibilities that this technique offers, further research on more types of feed is warranted, that would benefit industry and academia both.
Unique patterns of glycosylation in immunoglobulin subclass G4‐related disease and primary sclerosing cholangitis
Authors: Culver Emma L , van de Bovenkamp Fleur S , Derksen Ninotska I L , Koers Jana , Cargill Tamsin , Barnes Eleanor , de Neef Louise A , Koeleman Carolien A M , Aalberse Rob C , Wuhrer Manfred , Rispens Theo
Published: October 2018

Background and Aim

Immunoglobulin subclass G4‐related disease (IgG4‐RD) is characterized by an abundance of IgG4 antibodies in the serum and tissue. Glycosylation status of antibodies can impact on immune effector functions and disease pathophysiology. We sought to establish glycosylation patterns in a prospective cohort of patients with IgG4‐RD and the relationship with disease activity and response to treatment.

Methods

We assessed IgG Fc‐tail and Fab‐arm glycosylation status in patients with IgG4‐RD (n = 22), disease controls with primary sclerosing cholangitis (PSC) (n = 22), and healthy controls (n = 22). Serum IgG and subclasses were quantified using ELISA. Fc and Fab glycosylation were analyzed by mass spectrometry and lectin affinity chromatography, respectively. Disease activity, organ damage, and response to treatment were assessed using the IgG4 Responder Index.

Results

Immunoglobulin G Fab sialylation was increased in IgG4‐RD compared with PSC and healthy control (P = 0.01), with a preferential increase in IgG4‐specific Fab sialylation, which was independent of IgG4 Fab‐arm exchange. There was a reduction in IgG1‐specific Fc bisection and hybrid structures in IgG4‐RD (P < 0.01), which recovered upon steroid treatment and correlated with disease activity. Overall, IgG Fc galactosylation was reduced in both IgG4‐RD and PSC (P < 0.01), with a preferential reduction in IgG1‐specific sialylation and enhancement of IgG4‐specific bisection in PSC. IgG4 fucosylation and IgG1/2/3 hybrid structures negatively correlated with complement C3 and C4 levels in IgG4‐RD (P < 0.01), but not PSC.

Conclusion

We report the first study showing unique antibody glycosylation status in a prospective cohort of IgG4‐RD and PSC patients, which may determine modulation of the immune system and contribute to disease pathophysiology.
Incidence, inhospital mortality, and readmission among patients with alcoholic hepatitis in Korea: A nationwide study
Authors: Lee Jin Yong , Cho Yuri , Hong Min Hee , Kim Jayeun , Lee Dong Hyeon , Jung Yong Jin , Kim Byeong Gwan , Lee Kook Lae , Kim Won
Published: October 2018

Background and Aim

Alcoholic hepatitis (AH) ranks among the most costly diseases in South Korea. However, accurate hospitalization incidence rates, mortality rates, and contributing factors have not been investigated in South Korea. This study aimed to provide the nationwide incidence of hospitalization, inhospital mortality, and readmission rates for South Korean patients with AH.

Methods

Using the Korean Health Insurance Review and Assessment service database, a total of 39 800 inpatient cases from 2008 to 2012 were identified based on the International Classification of Diseases, 10th Revision diagnosis code for AH (K70.1). Standardized hospitalization incidence and mortality rates were calculated, and logistic regression analysis was performed to identify risk factors for inhospital mortality and readmission. Follow‐up data for those admitted in 2008 were collected to assess readmissions.

Results

The standardized incidence rate for AH hospitalization per 105 person/year decreased from 19 in 2008 to 14 in 2012 (P = 0.001). The annual inhospital mortality rate ranged from 0.2% to 0.5%. Inhospital mortality was significantly higher in older patients (odds ratio [OR], 1.36) and those with cirrhosis (OR, 4.40). The readmission rate for patients admitted in 2008 was 34.0%. Male sex (OR, 1.21) and low economic status (OR, 2.35) were significantly associated with readmission, whereas older age (OR, 0.96), cirrhosis (OR, 0.77), and urban residency (OR, 0.68) were inversely associated with readmission.

Conclusions

This study captured a 5‐year epidemiologic period in South Korea of patients with AH to reflect the real burden of AH and to provide valuable information to policy‐makers assessing public health priorities.
Disparities in the treatment of hepatocellular carcinoma based on geographical region are decreasing
Authors: Sobotka Lindsay A , Hinton Alice , Conteh Lanla F
Published: October 2018

Background and Aim

Geographic differences have existed in the management of hepatocellular carcinoma (HCC), and efforts to reduce regional disparities have been initiated. The aim of this study is to use the Nationwide Inpatient Sample to determine if regional disparities in the treatment of HCC continue to exist.

Method

A retrospective database analysis using the Nationwide Inpatient Sample was performed that included patients with a primary diagnosis of HCC. Logistic regression models were utilized to determine geographic disparities in liver decompensation, treatment, inpatient mortality, and metastatic disease.

Results

This study's locational reach of 62 604 patients included 22 769 patients from the South (36%), 14 554 in the Northeast (23%), 14 041 in the West (22%), and 11 240 in the Midwest (18%). Patients who received treatment in the West were more likely to have inpatient mortality (OR 1.28, 95% CI 1.03, 1.53) than patients who received treatment in the Midwest. No significant differences were observed between rates of resection, ablation, and transarterial chemoembolization when comparing by region. Rates of liver transplantation were lower in the West compared with the Midwest (OR 0.51, 95% CI 0.29, 0.87). There was no significant difference between other regions.

Conclusion

Geographic disparities in the treatment of HCC are improving.
Material Flow and Spatial Data Analysis of the Petroleum Use to Carbon Dioxide (CO2) Emissions in Northeast China
Authors: Liu Guang‐xin , Wu Ming , Jia Feng‐rui , Yue Qiang , Wang He‐ming
Published: October 2018

This study investigated the petroleum consumption and petroleum‐related CO2 emissions (PCOEs) in Northeast China at city level using material flow analysis (MFA) and spatial data analysis (SDA). The petroleum flows for the year 2014 were plotted, and then the spatial patterns, weighted mean centers (WMCs), and spatial autocorrelations of petroleum consumption and PCOEs were calculated, respectively. It was found that Northeast China is a petroleum exploitation‐processing‐export region in China; the total input of petroleum flows comprised two parts—exploitation (about 60%) and import (about 40%). About one third of the total product oil supply flowed into other provinces. In the consumption process, the product oil was dominated by two sectors: the industry sector (45.5%) and the transportation sector (31%). The rate of PCOEs was 36.69 million tonnes in the waste discharge process. Meanwhile, the WMCs of the petroleum consumption and the PCOEs were located in the south of Northeast China. The location of the petroleum pipelines was the factor shown to determine the spatial patterns of petroleum consumption and PCOEs and the hotspots were distributed along the petroleum pipeline, especially in the Circum‐Bohai Sea regions. Economic development in these regions shows a positive dependence on petroleum consumption and generates larger PCOEs. The findings obtained in this study could provide important decision‐making support to low‐carbon development in Northeast China.
Interest Rates and the Market for New Light Vehicles
Authors: COPELAND ADAM , HALL GEORGE , MACCINI LOUIS J.
Published: October 2018

We study the impact of interest rate changes on the demand and supply of new light vehicles in an environment where consumers and manufacturers face their own interest rates. Interest rate changes impact the auto market through both households and manufacturers. For the impact of rate changes on price and output growth, the household channel is quantitatively more important. A 100 basis‐point increase in both interest rates causes annual growth rates of production to fall from 1.0% to −11.0% and sales to fall from 1.0% to −2.9% in the short run.
Credit Traps and Macroprudential Leverage
Authors: FOULIS ANGUS , NELSON BENJAMIN , TANAKA MISA
Published: October 2018

We construct a macroeconomic model with overlapping generations to study credit traps—prolonged periods of stagnant real activity accompanied by low productivity, financial sector undercapitalization, and credit misallocation. Shocks to bank capital tighten banks' borrowing constraints causing them to allocate credit to easily collateralizable but low productivity projects. Low productivity weakens bank capital generation, reinforcing tight borrowing constraints, sustaining the credit trap steady state. Macroprudential policy to limit bank leverage can be welfare enhancing. In the presence of a credit trap, optimal leverage policy is countercyclical.
Where is the GE? Consumption Dynamics in DSGEs
Authors: L'HUILLIER JEAN‐PAUL , YOO DONGHOON
Published: October 2018

We offer a partial equilibrium perspective on the behavior of consumption in dynamic stochastic general equilibrium (DSGE) models. We consider a benchmark dynamic general equilibrium model and show that a standard calibration implies that the real interest rate is essentially fixed. One manifestation of this feature is that, with separable preferences, the reaction of consumption to total factor productivity (TFP) shocks is flat: the random‐walk permanent income hypothesis holds almost exactly, pretty much as in a partial equilibrium consumption‐savings problem. These results help explain the prominent role of aggregate demand, and how it is achieved, in modern DSGE analysis.
HDAC3 inhibition prevents oxygen glucose deprivation/reoxygenation‐induced transendothelial permeability by elevating PPARγ activity in vitro
Authors: Zhao Qiuchen , Yu Zhanyang , Zhang Fang , Huang Lena , Xing Changhong , Liu Ning , Xu Yun , Wang Xiaoying
Published: October 2018

Histone deacetylase 3 (HDAC3), a member of class I HDAC, regulates a wide variety of normal and abnormal physiological functions. Recent experimental studies suggested that inhibition of HDAC3 may increase acetylation of certain key signaling regulating proteins such as peroxisome proliferator‐activated receptor γ (PPARγ), which plays a crucial role in modulating cerebrovascular function and integrity. However, the role of HDAC3 inhibition in cerebrovascular endothelium function under pathological condition has not been fully investigated. In this study, we tested the hypothesis that inhibition of HDAC3 by RGFP966, a highly selective HDAC3 inhibitor, promotes PPARγ activation by enhancing its protein acetylation, resulting in protection of oxygen glucose deprivation and reoxygenation (OGD/R)‐induced increase of transendothelial cell permeability. In cultured primary human brain microvascular endothelial cells, our experimental results show that OGD/R increases transendothelial cell permeability and down‐regulates junction protein expression. While we also detected HDAC3 activity increase and PPARγ activity decline after OGD/R. However, treatment with RGFP966 significantly attenuated the OGD/R‐induced increase of transendothelial cell permeability and down‐regulation of tight junction protein Claudin‐5. These effects were observed to be dependent on HDAC3 activity inhibition‐mediated PPARγ protein acetylation/activation. Lastly, HDAC3 small interfering RNA mimics the protective effects of RGFP966 on human brain microvascular endothelial cells. Taken together, our data indicate that HDAC3 inhibition might comprise a new therapeutic target for reducing blood–brain barrier integrity disruption and vascular dysfunctions in neurological disorders.

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CAD/CAM Constructed Poly(etheretherketone) (PEEK) Framework of Kennedy Class I Removable Partial Denture: A Clinical Report
Authors: Harb Islam E. , Abdel‐Khalek Elsayed A. , Hegazy Salah A.
Published: October 2018

The prevalence of partially edentulous adults that could be treated by removable partial dentures (RPDs) is estimated to be greater than 20% in some regions of the United States. Problems related to traditional materials for RPD construction have been documented. Advances in polymer‐based materials and digital fabrication strategies would allow increased biocompatibility, durability, and elasticity, as well as more esthetically pleasing and cost‐effective benefits. This article reports on poly(etheretherketone) RPD framework produced by digital and milling technology.