bluuebunny/crossref_metadata_2025 huggingface dataset:
Total rioting: from metaphysics to politics
Authors: Truong Fabien
Published: November 2016

This article further develops understandings of urban riot as a social and political symptom to consider the riot as a situated and situating biographical moment, a personal experience which is both signifying and significant. It argues for a paired understanding of riots as a set of physical incarnated (re)actions and as ‘total social fact’ – involving ‘society as a whole’ and putting its institutions at work ‘all together and at once’ (Mauss, 1950). It switches from ‘urban riots’ as a descriptive notion to total rioting as an analytical tool. Total rioting consists of intertwined social upheavals and exchanges, writ through the metaphysical, sociological, poetical and political. It assembles people of a particular kind forever, hence manufacturing social solidarities and subjectivities. As a particular response to specific problems, it reveals how a contemporary state of metaphysical, social and political insecurity generates new forms of empowering projections and intimate policies; and why what is destroyed is precisely what matters. As an attempt to make and unmake society at the same time, it has become the pinnacle of a paradoxical political socialization process. Being less a language for a broader political communication than an insider trading activity, its long-term outcomes reshape the politics of recognition and claims for visibility.
Linking Issue Management, Corporate Social Responsibility and Crisis Communication: Applying Balance Theory in Crisis and Issue Management
Authors: Zhang Xiaochen Angela , Borden Jonathan
Published: November 2016

Through a 2 × 2 × 3 experiment design, this study examines effects of issue‐related corporate social responsibility (CSR) programmes on stakeholder perceptions of an issue‐related crisis (i.e., blame, scepticism and corporate credibility) through the lens of balance theory. Results indicate that issue‐related CSR programmes work well in reducing scepticism when stakeholders have high issue involvement and positive attitudes. Scepticism is also found to be a mediator between issue‐related CSR programmes and perceived corporate credibility.
Using Harm‐Based Weights for the AHRQ Patient Safety for Selected Indicators Composite (PSI‐90): Does It Affect Assessment of Hospital Performance and Financial Penalties in Veterans Health Administration Hospitals?
Authors: Chen Qi , Rosen Amy K. , Borzecki Ann , Shwartz Michael
Published: November 2016

Objective

To assess whether hospital profiles for public reporting and pay‐for‐performance, measured by the Agency for Healthcare Research and Quality (AHRQ) Patient Safety for Selected Indicators (PSI‐90) composite measure, were affected by using the recently developed harm‐based weights.

Data Sources/Study Setting

Retrospective analysis of 2012–2014 data from the Veterans Health Administration (VA).

Study Design

The AHRQ PSI software (v5.0) was applied to obtain the original volume‐based PSI‐90 scores for 132 acute‐care hospitals. We constructed a modified PSI‐90 using the harm‐based weights developed by AHRQ. We compared hospital profiles for public reporting and pay‐for‐performance between these two PSI‐90s and assessed patterns in these changes.

Principal Findings

The volume‐based and the harm‐based PSI‐90s were strongly correlated (r = 0.67, p < .0001). The use of the harm‐based PSI‐90 had a relatively small impact on public reporting (i.e., 5 percent hospitals changed categorization), but it had a much larger impact on pay‐for‐performance (e.g., 15 percent of hospitals would have faced different financial penalties under the Medicare Hospital‐Acquired Condition Reduction Program). Because of changes in weights of specific PSIs, hospital profile changes occurred systematically.

Conclusions

Use of the harm‐based weights in PSI‐90 has the potential to significantly change payments under pay‐for‐performance programs. Policy makers should carefully develop transition plans for guiding hospitals through changes in any quality metrics used for pay‐for‐performance.
Comparisons of morphology and esterase levels between Blattella germanica and Blattella nipponica (Blattodea: Blattellidae)
Authors: Kim Juil , Kwon Min , Maharjan Rameswor , Kim Gil‐Hah
Published: November 2016

The habitat of the cockroach varies by species. The German cockroach, Blattella germanica, lives in human dwellings, while the Japanese field roach, Blattella nipponica, lives in a mountainous region. Based on phylogenetic analysis of mtCOI, the two species are closely related to each other and B. germanica is divergent from wild species such as B. nipponica. Their habitats and walking speed differ even though the two species have similar morphology. We hypothesized that habitats might influence walking speed by changes to appendage morphology and enzyme‐based physiological differences. We compared the length of the appendages and differences in a multifunctional enzyme superfamily, the esterases (EST, EC 3.1), including acetylcholinesterase (AChE, EC 3.1.1.7), which is related to central nervous system function. We found that phenotypes such as appendage length and esterase isozyme expression were clearly different between the two species. These differences might be responsible for the observed difference in walking speed.
Partitioning the effects of mating and nuptial feeding on the microbiome in gift‐giving insects
Authors: Smith Chad C. , Srygley Robert B. , Dietrich Emma I. , Mueller Ulrich G.
Published: November 2016

Mating is a ubiquitous social interaction with the potential to influence the microbiome by facilitating transmission, modifying host physiology, and in species where males donate nuptial gifts to females, altering diet. We manipulated mating and nuptial gift consumption in two insects that differ in nuptial gift size, the Mormon cricket Anabrus simplex and the decorated cricket Gryllodes sigillatus, with the expectation that larger gifts are more likely to affect the gut microbiome. Surprisingly, mating, but not nuptial gift consumption, affected the structure of bacterial communities in the gut, and only in Mormon crickets. The change in structure was due to a precipitous drop in the abundance of lactic‐acid bacteria in unmated females, a taxon known for their beneficial effects on nutrition and immunity. Mating did not affect phenoloxidase or lysozyme‐like antibacterial activity in either species, suggesting that any physiological response to mating on host‐microbe interactions is decoupled from systemic immunity. Protein supplementation also did not affect the gut microbiome in decorated crickets, suggesting that insensitivity of gut microbes to dietary protein could contribute to the lack of an effect of nuptial gift consumption. Our study provides experimental evidence that sexual interactions can affect the microbiome and suggests mating can promote beneficial gut bacteria.
Termination of pre‐hospital resuscitation by anaesthesiologists – causes and consequences. A retrospective study
Authors: Mikkelsen S. , Lossius H. M. , Binderup L. G. , Schaffalitzky de Muckadell C. , Toft P. , Lassen A. T.
Published: November 2016

Aim

Differentiating between a newly deceased patient and the lifeless patient in whom immediate resuscitation is required may be facilitated by a pre‐hospital anaesthesiologist. The purpose of our study was to investigate to what extent and why the pre‐hospital anaesthesiologist pronounced life extinct in situations where an emergency medical technician (EMT) would have been required to resuscitate.

Methods

All lifeless patients seen pre‐hospitally by the anaesthesiologist‐manned Mobile Emergency Care Unit in Odense, Denmark, from 2010 to 2014 were retrospectively studied.

Results

Of 17 035 contacts, 1275 patients were lifeless without reliable signs of death. In 642 of these patients (3.8%) resuscitation was initiated (median age 68 years). The remaining 633 patients (3.7%) were declared dead at the scene without any resuscitation attempt (median age 77 years). These latter patients would have been attempted resuscitated, had the anaesthesiologist not been present. In 54.5% of cases where documentation was available in the patient records, reasons for not resuscitating these patients included time elapsed from incident to contact with physician, ‘overall assessment’, chronic disease, or do‐not‐resuscitate order.

Conclusion

In one patient in 30, the MECU refrained from futile resuscitation in cases where legislation required an EMT to initiate resuscitation. This practice reduced unethical attempts of resuscitation, reduced unnecessary emergency ambulance transports, and reduced the work load of the hospital resuscitation teams for one unnecessary alarm every third day. Differentiating between lifeless patients and dead patients not exhibiting reliable signs of death, however, is a complex task which is only sparsely documented.
Funding Research in Emergency Department Shared Decision Making: A Summary of the 2016 Academic Emergency Medicine Consensus Conference Panel Discussion
Authors: Dodd Kenneth W. , Berman Amy , Brown Jeremy , Carr Brendan G. , Dunn Patrick , Escobedo Marcus , Gayer Christopher , Grieser Mira , Carpenter Christopher R. , Hess Erik P. , Grudzen Corita R.
Published: November 2016

As part of the 2016 Academic Emergency Medicine Consensus Conference, “Shared Decision Making in the Emergency Department: Development of a Policy‐relevant Patient‐centered Research Agenda,” a panel of representatives from the Office of Emergency Care Research, the Patient‐Centered Outcomes Research Institute, the American Heart Association, the John A. Hartford Foundation, and the Emergency Care Coordination Center were assembled to discuss funding opportunities for future research in this field. This article summarizes their discussion of funding priorities and examples of successfully funded projects related to shared decision making in emergency medicine.
Translocation and hand‐rearing result in short‐tailed albatrosses returning to breed in the Ogasawara Islands 80 years after extirpation
Authors: Deguchi T. , Sato F. , Eda M. , Izumi H. , Suzuki H. , Suryan R. M. , Lance E. W. , Hasegawa H. , Ozaki K.
Published: November 2016

Restoration or establishment of colonies using translocation and hand‐rearing can be an effective tool for conserving birds. However, well‐designed post‐release evaluation studies for long‐lived species are rarely implemented. We investigated the attendance and breeding attempts of hand‐reared short‐tailed albatross (STAL) Phoebastria albatrus chicks (n = 69) translocated to a historic breeding island in the Ogasawara Islands, 350 km from the source colony, for 8 consecutive years after the first translocation. Thirty‐nine percent of hand‐reared birds (n = 27) returned to the translocation site at least once per breeding season, of which 67% (n = 18) also visited the natal island. The number of hand‐reared birds returning each year was lower at the translocation site (mean: 0.3–2.3 birds per day) versus the natal island (0.4–3.5 birds per day). The first breeding attempt occurred 5 years after the first translocation. Three pairs (producing three chicks) recruited to the translocation site or neighboring islands and five pairs (producing nine chicks) recruited to the natal island by 8 years after the first translocation. Every hand‐reared bird that raised a chick paired with a naturally reared bird. At the translocation site and neighboring islands, two hand‐reared birds paired with a mate from the natal island and a breeding colony 1850 km away, respectively, while the parents of the third chick were unknown. Their breeding at the translocation region was observed among conspecific social attractants (decoys, audio playback; one pair) or congeners (two pairs). Our preliminary results suggest that even though more translocated and hand‐reared albatrosses visited and recruited to their natal island compared to the translocation site, the early re‐establishment of breeding by short‐tailed albatrosses in the Ogasawara Islands 80 years after extirpation would not have occurred without the initial translocation effort. Further study is needed, however, to fully understand formation of breeding colonies beyond conspecific attraction and philopatry.
The implications of biodiversity loss for the dynamics of wildlife in Australia
Authors: Ward‐Fear G. , Hayward M. W. , L'Hotellier F. , Herman K. , Kabat A. P. , Gibbons J. P.
Published: November 2016

This article is corrected by:

Errata: Erratum for ‘Could biodiversity loss have increased Australia's bushfire threat?’ and ‘The implications of biodiversity loss for the dynamics of wildlife in Australia’ | Volume 20, Issue 2, 213, Article first published online: 3 April 2017
Cue‐induced nicotine‐seeking behavior after withdrawal with or without extinction in rats
Authors: Markou Athina , Li Jie , Tse Kearny , Li Xia
Published: November 2016

Exposure to smoking‐associated environmental cues during smoke cessation elicits self‐reported urge/craving to smoke, which precipitates relapse even after prolonged abstinence. Incubation of cue‐induced cigarettes craving during abstinence has been observed in human smokers recently. The present studies assessed cue‐induced nicotine‐seeking behavior under different withdrawal conditions in rats with a history of nicotine self‐administration. We found that non‐reinforced operant responding during cue‐induced nicotine seeking after different periods of withdrawal from nicotine exhibited an inverted U‐shaped curve, with higher levels of responding after 7–21 days of withdrawal than those after 1‐day withdrawal. Cue‐induced nicotine‐seeking responding is long lasting and persists even after 42 days of forced withdrawal in the home cages. Interestingly, repeated testing of cue‐induced nicotine seeking at different withdrawal time points (1, 7, 14, 21 and 42 days) in the same individual alleviated responding as compared with the between‐subjects assessment. Furthermore, extinction training during nicotine withdrawal significantly decreased cue‐induced reinstatement of nicotine‐seeking behavior. Together, profound time‐dependent incubation of cue‐induced craving in nicotine‐experienced rats were observed. In addition, repeated cue exposure or extinction training decreases cue‐induced craving. The demonstration of incubation of nicotine craving phenomenon in both rat and human studies provides support for the translational potential of therapeutic targets for relapse uncovered through mechanism studies in rats.
Alcohol's contribution to cancer is underestimated for exactly the same reason that its contribution to cardioprotection is overestimated
Authors: Stockwell Tim , Zhao Jinhui
Published: November 2016

Commentary to: Alcohol consumption as a cause of cancer
Extracorporeal Membrane Oxygenation Support in Trauma Versus Nontrauma Patients with Noninfectious Acute Respiratory Failure
Authors: Kim Hyoung Soo , Ha Sang Ook , Han Sang Jin , Kim Hyun‐Sook , Lee Sun Hee , Jung Ki‐Suck , Park Sunghoon
Published: November 2016

The utility of extracorporeal membrane oxygenation (ECMO) in patients with acute respiratory distress syndrome (ARDS) of noninfectious origin remains unclear. Data on patients with ARDS of noninfectious origin who underwent ECMO were reviewed retrospectively. We compared the pre‐ECMO characteristics and hospital outcomes of patients with traumatic and nontraumatic ARDS. In total, 23 patients (trauma, n = 9; nontrauma, n = 14) were included in the study. The mean patient age was 42 years, there were three females, and the mean pre‐ECMO Simplified Acute Physiologic Score (SAPS) II was 60.0 (49.0–71.0). The hemoglobin level was lower and the prothrombin time (PT) more prolonged, prior to initiation of ECMO, in traumatic compared with nontraumatic ARDS patients. During the first 48 h of ECMO support, the coagulation parameters did not differ between the two groups, but the platelet counts, PT, and activated partial thromboplastin time indicated that coagulopathy was developing in all patients. The hospital and 28‐day mortality rates were 21.7 and 13.0%, respectively, and serious neurological outcomes (cerebral performance category [CPC] of three points or more) developed in 26.1% of all patients; however, the extent of such outcomes did not differ between traumatic and nontraumatic ARDS patients. Upon multivariate analysis, the pre‐ECMO SAPS II tended to be associated with composite events (i.e., hospital death and/or a CPC of three points or more) (P = 0.051). Additionally, a history of hypertension and an elevated pre‐ECMO SAPS II were significant risk factors for serious neurological outcomes among hospital survivors (n = 18). In conclusion, ECMO support can be associated with favorable outcomes in patients with ARDS of noninfectious origin, irrespective of whether the ARDS is associated with trauma. The pre‐ECMO SAPS II and a history of hypertension may be independent risk factors for poor outcomes.
Randomised clinical trial: efficacy and safety of vonoprazan vs. lansoprazole in patients with gastric or duodenal ulcers – results from two phase 3, non‐inferiority randomised controlled trials
Authors: Miwa H. , Uedo N. , Watari J. , Mori Y. , Sakurai Y. , Takanami Y. , Nishimura A. , Tatsumi T. , Sakaki N.
Published: November 2016

Background

Vonoprazan is a new potassium‐competitive acid blocker for treatment of acid‐related diseases.

Aim

To conduct two randomised‐controlled trials, to evaluate the non‐inferiority of vonoprazan vs. lansoprazole, a proton pump inhibitor, for treatment of gastric ulcer (GU) or duodenal ulcer (DU).

Methods

Patients aged ≥20 years with ≥1 endoscopically‐confirmed GU or DU (≥5 mm white coating) were randomised 1:1 using double‐dummy blinding to receive lansoprazole (30 mg) or vonoprazan (20 mg) for 8 (GU study) or 6 (DU study) weeks. The primary endpoint was the proportion of patients with endoscopically confirmed healed GU or DU.

Results

For GU, 93.5% (216/231) of vonoprazan‐treated patients and 93.8% (211/225) of lansoprazole‐treated patients achieved healed GU; non‐inferiority of vonoprazan to lansoprazole was confirmed [difference = −0.3% (95% CI −4.750, 4.208); P = 0.0011]. For DU, 95.5% (170/178) of vonoprazan‐treated patients and 98.3% (177/180) of lansoprazole‐treated patients achieved healed DU; non‐inferiority to lansoprazole was not confirmed [difference = −2.8% (95% CI −6.400, 0.745); P = 0.0654]. The incidences of treatment‐emergent adverse events were slightly lower for GU and slightly higher for DU with vonoprazan than with lansoprazole. There was one death (subarachnoid haemorrhage) in the vonoprazan group (DU). The possibility of a relationship between this unexpected patient death and the study drug could not be ruled out. In both studies, increases in serum gastrin levels were greater in vonoprazan‐treated vs. lansoprazole‐treated patients; levels returned to baseline after treatment in both groups.

Conclusions

Vonoprazan 20 mg has a similar tolerability profile to lansoprazole 30 mg and is non‐inferior with respect to GU healing and has similar efficacy for DU healing.
Effects of oils on feed mildew and quality
Authors: Liu Jie , Qi Ming , Huang Yakuan , Guo Jiao , Zhang Jiacai , Li Chong , Zhang Niya , Sun Lvhui , Qi Desheng
Published: November 2016

This study was performed to determine the effects of oils on feed mildew and feed quality. Under different moisture content conditions (10%, 13% and 16%), the basal feeds were supplemented with 4%, 6%, 8%, 10% and 12% soybean oil. In addition, at different moisture content levels (10%, 13% and 16%), the basal feed was supplemented with 12% of various types of oil (soybean, peanut, corn and fish). Subsequently, a mixed mold spore suspension was added. The feed samples were incubated at 28°C, and the total mold, water activity (Aw), moisture, acid value, crude protein (CP), crude lipid (CL), crude ash (CA) and nitrogen‐free extract (NFE) levels were determined at 15, 30, 45 and 60 days. The results showed no significant variations in the feed moisture, CP, CL, CA and NEF contents. However, the acid value gradually increased in the feed samples with an extended incubation time and increasing initial moisture. The feed moisture content was a critical factor controlling feed mildew, and high levels of oil supplementation caused an elevated Aw. Additionally, peanut oil promoted mold growth in feed. These results provide a reference for the production and scientific management of formulated feed.
A systematic review of the outcomes reported in trials of medication review in older patients: the need for a core outcome set
Authors: Beuscart Jean‐Baptiste , Pont Lisa G. , Thevelin Stefanie , Boland Benoit , Dalleur Olivia , Rutjes Anne W. S. , Westbrook Johanna I. , Spinewine Anne
Published: November 2016

Aim

Medication review has been advocated as one of the measures to tackle the challenge of polypharmacy in older patients, yet there is no consensus on how best to evaluate its efficacy. This study aimed to assess outcome reporting in trials of medication review in older patients.

Methods

Randomized controlled trials (RCTs), prospective studies and RCT protocols involving medication review performed in patients aged 65 years or older in any setting of care were identified from: (1) a recent systematic review; (2) RCT registries of ongoing studies; (3) the Cochrane library. The type, definition, and frequency of all outcomes reported were extracted independently by two researchers.

Results

Forty‐seven RCTs or prospective published studies and 32 RCT protocols were identified. A total of 327 distinct outcomes were identified in the 47 published studies. Only one fifth (21%) of the studies evaluated the impact of medication reviews on adverse events such as drug reactions or drug‐related hospital admissions. Most of the outcomes were related to medication use (n = 114, 35%) and healthcare use (n = 74, 23%). Very few outcomes were patient‐related (n = 24, 7%). A total of 248 distinct outcomes were identified in the 32 RCT protocols. Overall, the number of outcomes and the number and type of health domains covered by the outcomes varied largely.

Conclusion

Outcome reporting from RCTs concerning medication review in older patients is heterogeneous. This review highlights the need for a standardized core outcome set for medication review in older patients, to improve outcome reporting and evidence synthesis.
Characterization of adverse drug reactions causing admission to an intensive care unit
Authors: Rojas‐Velandia Camilo , Ruiz‐Garzón Jair , Moscoso‐Alcina Juan‐Carlos , Vallejos‐Narvaéz Álvaro , Castro‐Canoa Jenny , Bustos‐Martínez Yuri , Flórez‐Cutiva Max , Contreras‐Muñoz Mabel , Gómez‐Gil Jully‐Carolina , Calderón‐Ospina Carlos‐Alberto
Published: December 2016

Aims

This study aimed to determine the occurrence of adverse drug reactions (ADRs) that caused admission to the intensive care unit (ICU) of a university hospital.

Methods

Clinical records were reviewed for patients meeting the inclusion criteria who were admitted to the ICU between September and December 2012. Suspected cases of ADRs were documented. Nine researchers later evaluated causality using the Naranjo Algorithm, preventability using the Schumock and Thornton criteria, and clinical classification based on the dose–time–susceptibility system.

Results

In total, 96 patients presented 108 cases of ADR (13.8%, 95% confidence interval 11.2–16.4%) as the cause of admission. The most frequent ADRs were bradyarrhythmias and upper gastrointestinal bleeding (12%). Therapeutic failure accounted for 20%. The most commonly associated medications were acetylsalicylic acid (16%) and losartan (10%). Forty‐six cases were categorized as possible, and only one as definite. According to the dose–time–susceptibility classification, in 82% of the cases, the dosage was collateral (within the therapeutic range), and 90% were independent of time; the factors most associated with susceptibility to ADRs were comorbidities (42%) and age (49%). Forty‐four percent of the ADRs were considered possibly preventable.

Conclusions

ADRs contribute significantly to ICU admissions, and a significant number of ADRs are preventable. National studies are needed to assess their incidence and to establish classification standards to reduce their clinical impact.
The use of anthracyclines in the treatment of endemic Burkitt lymphoma
Authors: Molyneux Elizabeth , Schwalbe Ed , Chagaluka George , Banda Kondwani , Israels Trijn , Depani Sarita , Mittermayer‐Vassallo Kirstin , Windebank Kevin , Mvula Jessie , Njiram'madzi Jenala , O'Brien Stephen , Carey Peter , Bailey Simon
Published: November 2016

Burkitt lymphoma is the most common malignancy in children in Malawi, the world's poorest country, where there is a long history of treating this disease using a 28‐day cyclophosphamide‐based protocol. Stage III/IV disease has had poor outcomes. In an attempt to improve the outcome for higher stage disease, anthracyclines were added to the existing protocol. The disease‐free (DFS) and overall survival (OS) of 58 children with cytologically confirmed Burkitt lymphoma admitted during 2012–2014 and treated using this protocol were calculated. Six (10%) children had stage I disease, ten (17%) stage II and 42 stage III or IV (73%). Overall 12‐month DFS (OS) was 68·5% (72·9%); for stage I disease 100% (100%), stage II 56·2% (60%), stage III/IV 66·3% (72·2%). The DFS was significantly improved from the previous protocol (P = 8 × 10−4). The addition of doxorubicin to stage III and IV disease resulted in a markedly improved DFS. Anthracyclines are deliverable in resource‐poor settings and possibly improve the survival of children with Burkitt lymphoma.
DEFINING RELEVANT MARKETS FOR PHARMACEUTICALS
Authors: Mihaescu Oana , Rudholm Niklas
Published: November 2016

To identify the relevant product markets for Swedish pharmaceuticals, a spatial econometrics approach is employed. First, we calculate Moran's Is for different market definitions and then we use a spatial Durbin model to determine the effect of price changes on quantity sold of own and competing products. As expected, the results show that competition is strongest between close substitutes; however, the relevant product markets for Swedish pharmaceuticals extend beyond close substitutes down to products included in the same class on the four‐digit level of the Anatomic Therapeutic Chemical system as defined by the World Health Organization. The spatial regression model further indicates that increases in the price of a product significantly lower quantity sold of that product and in the same time increase the quantity sold of competing products. For close substitutes (products belonging to the same class on the seven‐digit level of the Anatomic Therapeutic Chemical system), as well as for products that, without being close substitutes, belong to the same therapeutic/pharmacological/chemical subgroup (the same class on the five‐digit level of the Anatomic Therapeutic Chemical system), increased competition is also visible after 1 July 2009 when the latest policy changes with regards to pharmaceuticals have been implemented in Sweden.
OSLsignal resetting in young deposits determined with a pulsed photon‐stimulated luminescence (PPSL) unit
Authors: Muñoz‐Salinas Esperanza , Castillo Miguel , Arce José Luis
Published: December 2016

Optical Stimulated Luminescence (OSL) is a technique that can be used for dating geological materials deposited within the last half‐million years, including sediments transported by air, water or gravity, as well as rocks heated at high temperatures. Recently, several studies have shown thatOSLcan also provide information on sediment transport. The pulsed photon‐stimulated luminescence (PPSL) unit (also known as a portableOSLreader) developed by the Scottish Universities Environmental Research Centre is an instrument designed to read luminescence signals from bulk (untreated) sediment samples comprising poly‐mineral and poly‐grain fractions. In this contribution, we evaluate the potential of thePPSLunit to assess the degree ofOSLsignal resetting in 27 young deposits (<2 ka) transported by different geomorphic agents in volcanic, coastal and fluvial depositional settings located in Mexico. Our results are in agreement with previous findings that used the RisøTL/OSLreader, confirming that sediments transported by debrisflows contain the highest inherited luminesce signals. Infrared stimulation (IRSL) values in volcanic ash, lavas, and sand beach and dune deposits exhibit low scatter. However, with blue stimulation (BLSL) these samples reveal a large degree of scattering, attributed to charge transfer in the case of the coastal deposits and to the low sensitivity of quartz in the case of volcanic material. The luminescence signals of fluvial sediments exhibit a highly scattered distribution in bothIRSLandBLSL. We conclude that the use of aPPSLunit is a simple approach to assess the degree ofOSLsignal resetting in deposits sourced from different geological environments. This research contributes to previous studies that have investigated new applications of thePPSLunit to assist inOSLdating of geological materials.
Critical roles of conventional dendritic cells in promoting T cell-dependent hepatitis through regulating natural killer T cells
Authors: Wang J , Cao X , Zhao J , Zhao H , Wei J , Li Q , Qi X , Yang Z , Wang L , Zhang H , Bai L , Wu Z , Zhao L , Hong Z , Yin Z
Published: November 2016

Dendritic cells (DCs) play critical roles in initiating and regulating innate immunity as well as adaptive immune responses. However, the role of conventional dendritic cells (cDCs) in concanavalin A (ConA)-induced fulminant hepatitis is unknown. In this study, we demonstrated that depletion of cDCs using either CD11c-diphtheria toxin receptor transgenic mice (DTR Tg) mice or anti-CD11c antibody reduced the severity of liver injury significantly, indicating a detrimental role of cDCs in ConA-induced hepatitis. We elucidated further the pathological role of cDCs as being the critical source of interleukin (IL)-12, which induced the secretion of interferon (IFN)-γ by natural killer (NK) T cells. Reconstitution of cDCs-depleted mice with IL-12 restored ConA-induced hepatitis significantly. Furthermore, we determined that NK T cells were the target of DC-derived IL-12, and NK T cells contributed to liver inflammation and injury through production of IFN-γ. In summary, our study demonstrated a novel function of cDCs in mediating ConA-induced hepatitis through regulating IFN-γ secretion of NK T cells in an IL-12-dependent fashion. Targeting cDCs might provide potentially therapeutic applications in treating autoimmune related liver diseases.
Bi‐allelic IARS mutations in a child with intra‐uterine growth retardation, neonatal cholestasis, and mild developmental delay
Authors: Orenstein N. , Weiss K. , Oprescu S.N. , Shapira R. , Kidron D. , Vanagaite‐Basel L. , Antonellis A. , Muenke M.
Published: November 2016

Recently, bi‐allelic mutations in cytosolic isoleucyl‐tRNA synthetase (IARS) have been described in three individuals with growth delay, hepatic dysfunction, and neurodevelopmental disabilities. Here we report an additional subject with this condition identified by whole‐exome sequencing. Our findings support the association between this disorder and neonatal cholestasis with distinct liver pathology. Furthermore, we provide functional data on two novel missense substitutions and expand the phenotype to include mild developmental delay, skin hyper‐elasticity, and hypervitaminosis D.
Sorafenib and azacitidine as salvage therapy for relapse of FLT3‐ITD mutated AML after allo‐SCT
Authors: Rautenberg Christina , Nachtkamp Kathrin , Dienst Ariane , Schmidt Pia Verena , Heyn Claudia , Kondakci Mustafa , Germing Ulrich , Haas Rainer , Kobbe Guido , Schroeder Thomas
Published: November 2016

Objective

Patients with acute myeloid leukemia (AML) carrying FLT3‐ITD mutations (FLT3‐ITD+) who relapse after allogeneic transplantation (allo‐SCT) have a very dismal prognosis with the currently available treatment options.

Methods

We treated eight patients with FLT3‐ITD+ AML who had relapsed in median 91 d (range, 28–249) following allo‐SCT with a combination of the multikinase inhibitor sorafenib and the DNA methyltransferase inhibitor azacitidine (Aza).

Results

Patients received a median of five cycles of Aza (range, 2–9) and sorafenib with a median daily dosage of 750 mg (range 400–800) for 129 d (range, 61–221). Six of eight patients received donor lymphocyte infusions (DLI) with a median number of two DLI per patient (range, 1–4). Following this treatment, four patients (50%) achieved a complete remission and three of them a complete molecular remission. Median duration of CR was 182 d (range, 158–406), and two patients remain in ongoing remission for 406 and 168 d. Median overall survival was 322 d (range, 108–574 d) with three patients being currently alive.

Conclusion

Taken together, the combination of sorafenib, Aza, and DLI shows promising efficacy and deserves further evaluation in larger patient groups.
Salvage therapy in first relapse: a retrospective study in a large patient population with multiple myeloma
Authors: Offidani Massimo , Corvatta Laura , Bringhen Sara , Gentili Silvia , Troia Rossella , Maracci Laura , Larocca Alessandra , Gay Francesca , Leoni Pietro , Boccadoro Mario
Published: November 2016

Objective

There is no strong evidence to guide therapeutic approach to multiple myeloma (MM) patients who experience first relapse. The treatment choice can be difficult since currently all patients are exposed to novel agents as thalidomide, bortezomib and lenalidomide.

Methods

In this retrospective analysis, we evaluated the best therapeutic sequence, the role of retreatment, and the most beneficial cutoff of first remission in order to choose retreatment, analyzing 476 patients relapsed after first‐line therapy.

Results

Bortezomib‐based regimens upfront followed by lenalidomide‐based regimens at first relapse resulted in significantly better second progression‐free survival (2ndPFS), PFS2, and overall survival (OS) compared to the opposite sequence. Changing therapy resulted in significantly better 2ndPFS in the whole population, whereas PFS2 was significantly longer only in patients who underwent maintenance therapy. Moreover, until PFS1 was shorter than 27 months, changing therapy at first relapse significantly extended 2ndPFS and PFS2 compared to retreatment, whereas similar outcomes were observed between the two strategies, when PFS1 was longer than 27 months.

Conclusion

Lacking randomized trials, our study could help to choose the most appropriate therapy algorithm in patients with MM.
Spectral summation and facilitation in on‐ and off‐responses for optimized representation of communication calls in mouse inferior colliculus
Authors: Akimov Alexander G. , Egorova Marina A. , Ehret Günter
Published: November 2016

Selectivity for processing of species‐specific vocalizations and communication sounds has often been associated with the auditory cortex. The midbrain inferior colliculus, however, is the first center in the auditory pathways of mammals integrating acoustic information processed in separate nuclei and channels in the brainstem and, therefore, could significantly contribute to enhance the perception of species’ communication sounds. Here, we used natural wriggling calls of mouse pups, which communicate need for maternal care to adult females, and further 15 synthesized sounds to test the hypothesis that neurons in the central nucleus of the inferior colliculus of adult females optimize their response rates for reproduction of the three main harmonics (formants) of wriggling calls. The results confirmed the hypothesis showing that average response rates, as recorded extracellularly from single units, were highest and spectral facilitation most effective for both onset and offset responses to the call and call models with three resolved frequencies according to critical bands in perception. In addition, the general on‐ and/or off‐response enhancement in almost half the investigated 122 neurons favors not only perception of single calls but also of vocalization rhythm. In summary, our study provides strong evidence that critical‐band resolved frequency components within a communication sound increase the probability of its perception by boosting the signal‐to‐noise ratio of neural response rates within the inferior colliculus for at least 20% (our criterion for facilitation). These mechanisms, including enhancement of rhythm coding, are generally favorable to processing of other animal and human vocalizations, including formants of speech sounds.
Toxic effects of human and rodent variants of alpha‐synuclein in vivo
Authors: Landeck Natalie , Buck Kerstin , Kirik Deniz
Published: November 2016

In Parkinson's disease, abnormal alpha‐synuclein (asyn) accumulation leads to the formation of soluble oligomeric species thought to be toxic to cells as well as intraneuronal inclusions. To date, the precise mechanisms leading to aggregation of asyn in the brain is not well‐understood. Previous studies in yeast, drosophila, and transgenic mice suggested that a non‐A beta component depleted version of human asyn [h‐asyn(D70‐83)] or human beta‐synuclein (h‐bsyn), naturally lacking this centrally located hydrophobic region, are less prone to form aggregates in vitro and are expected to be less toxic compared to h‐asyn in vivo, although not all experimental studies unequivocally support the latter view. To address this outstanding issue, we directly compared the neurotoxicity of human asyn against that of h‐asyn(D70‐83), h‐bsyn as well as rat asyn using an adeno‐associated viral vector to express these proteins in a dose‐response study where the vector load was varied over two orders of magnitude. By quantifying the neurodegeneration of rat substantia nigra dopamine neurons here we show that h‐asyn, h‐bsyn, and h‐asyn(D70‐83) display comparable neurotoxicity across the vector doses tested. On the other hand, rat asyn and GFP control vectors displayed a different profile, where no detectable neurodegeneration was seen except at the highest vector titer. Thus, the two main conclusions of our study are that (i) deletion of the central hydrophobic region in h‐asyn is not sufficient to alter its neurotoxic properties and (ii) expression of the widely used GFP control protein can cause measurable neurodegeneration at high titers.
A Comedy We Believe In: A Further Look at Sartre's Theory of Emotions
Authors: Hartmann Martin
Published: December 2016

This paper discusses recent interpretations of Jean‐Paul Sartre's early theory of emotions, in particular his Sketch for a Theory of the Emotions. Despite the great interest that Sartre's approach has generated, most interpretations assume that his approach fails because it appears to be focussed on ‘malformed’, ‘irrational’ or ‘distorted’ emotions. I argue that these criticisms adopt a rationalistic or epistemically biassed perspective on emotions that is wrongly applied to Sartre's text. In my defence of Sartre I show that the directional fit of emotions is not towards an evaluatively loaded world which is independently given and, at best, represented by emotions, but towards a world shaped through the impact of emotions themselves. Sartre's idea of emotions ‘magically transforming’ reality for the subject so that the latter is better able to cope with problematic aspects of practically relevant situations encapsulates the world‐shaping capacities of emotions, which are thus not reserved for a restricted class of emotions. Recognition of the transformative powers of emotions will also direct attention away from their seemingly representative elements to their normative and practical aspects and offer a new basis for delineating the criteria for judging them. The plausibility of this position is discussed with reference to some of Sartre's examples, such as fear, sadness and horror, but also with reference to Joan Didion's account of grief in The Year of Magical Thinking.
An advanced mouse model for human skin wound healing
Authors: Wen Jie , Li Xiangyong , Leng Xue , Xu Xin , Wu Xunwei
Published: November 2016

Here, we report a model for studying wound repair based on skin regenerated from human tissue culture‐expanded cells. The reconstituted skin (hRSK) responds to injury similar to that of intact human skin, and its constituent cells contribute to the healing process. As we have demonstrated that hRSK composed of GFP‐labelled cells also heals “normally,” we believe this model will be useful in analysing the wound repair process using genetically modified human cells.
Crack propagation models: numerical and experimental results on Ti–6Al–4V notched specimens
Authors: Baragetti S , Villa F
Published: December 2016

To investigate on corrosion fatigue, a reliable crack propagation rate model has to be adopted, along with a suitable fracture mechanics model, to decouple the mechanical contribution from the environmental effects. In the present work, a numerical algorithm is proposed to characterize the mechanical behaviour of notched Ti–6Al–4V specimens for fatigue and corrosion fatigue tests. The method is based on theoretical crack propagation rate models, jointly with stress intensity factor range obtained from linear finite element models. Results are compared with experimental data for axial fatigue (R = 0.1) and theoretical models for fatigue crack growth, such as Paris, Walker and Kato.
Improvement in the dissolved oxygen concentration and water exchange in Ofunato Bay, Japan, after the collapse of the bay‐mouth breakwater by the 2011 Tohoku Earthquake and tsunami
Authors: Kakehi Shigeho , Kamiyama Takashi , Kaga Yoshimasa , Naiki Kimiaki , Kaga Shinnosuke
Published: November 2016

Oyster and scallop aquaculture has flourished in Ofunato Bay, on the Sanriku Coast of Japan. Between 1967 and 2011, this bay was a highly enclosed area by a bay‐mouth breakwater, and while the breakwater provided calm conditions suitable for aquaculture, there was concern about water quality deterioration. The Tohoku Earthquake off the Pacific coast and the subsequent major tsunami on 11 March 2011 caused extensive damage to the Sanriku Coast, resulting in the collapse of the breakwater of Ofunato Bay. We analyzed the monthly hydrographic observational data that were collected between 1996 and 2015, supplemented with hydrographic observations and direct current measurements that were carried out after the earthquake. The historical hydrographic observational data showed the lowest dissolved oxygen (DO) concentrations were observed near the bottom in the bay. The average and standard deviation of the lowest DO concentrations of each monthly observation during the period before and after the earthquake were 5.81 ± 3.72 and 7.22 ± 1.49 mg L−1, respectively, and are significantly different. The oceanic water inflow and water exchange rate estimated by a box model based on the salt budget under the steady‐state estuarine circulation were also significantly different before and after the earthquake. An increase in the inflow of oceanic water and the more rapid water exchange in the bay after the earthquake induced marked improvements in the bottom DO concentration. These changes are considered to be attributable to the improved circulation of oceanic water in the bay that resulted from the collapse of the bay‐mouth breakwater.
The relationship between oestrogen receptor‐alpha phosphorylation and the tumour microenvironment in patients with primary operable ductal breast cancer
Authors: Cheng Kelvin K W , Dickson Ashley , Gujam Fadia J A , McMillan Donald C , Edwards Joanne
Published: November 2016

Aims

Although the role of phosphorylation of oestrogen receptor (ER) at serines 118 (p‐S118) and 167 (p‐S167) has been studied, the relationship between p‐S118, p‐S167 and the tumour microenvironment in ER‐positive primary operable ductal breast cancers have not been investigated. The aims of this study are to investigate (i) the relationship between p‐S118/p‐S167 and the tumour microenvironment, and (ii) the effect of p‐S118/167 on survival and recurrence in ER‐positive primary operable ductal breast cancers.

Methods and results

Patients presenting at three Glasgow hospitals between 1995 and 1998 with invasive ductal ER‐positive primary breast cancers were studied (n = 294). Immunohistochemical staining of p‐S118 and p‐S167 was performed and their association with clinicopathological characteristics, cancer‐specific survival (CSS) and recurrence‐free interval (RFI) were examined. In the whole cohort, tumour size (P < 0.05) and microvessel density (P < 0.05) were associated with high p‐S118 while increased micovessel density (P < 0.05), apoptosis (P < 0.05), general inflammatory infiltrate measured using the Klintrup–Makinen score (P < 0.05) and macrophage infiltrate (P < 0.05) were found to be associated with high p‐S167. Only high p‐S167 was associated with shorter CSS (P < 0.005) and shorter RFI in the whole cohort (P = 0.001) and separately in the luminal A (P < 0.05) and B tumours (P < 0.05).

Conclusions

This study showed that both p‐S118 and p‐S167 were associated with several microenvironmental factors, including increased microvessel density. In particular, p‐S167 was associated with reduced RFI and CSS in the whole cohort and RFI in luminal A and B tumours and could possibly be employed to predict response to kinase inhibitors.
New curricular design in biostatistics to prepare residents for an evidence‐based practice and lifelong learning education: a pilot approach
Authors: Arias A. , Peters O. A. , Broyles I. L.
Published: November 2016

Aim

To develop, implement and evaluate an innovative curriculum in biostatistics in response to the need to foster critical thinking in graduate healthcare education for evidence‐based practice and lifelong learning education.

Methodology

The curriculum was designed for first‐year residents in a postgraduate endodontic programme using a six‐step approach to curriculum development to provide sufficient understanding to critically evaluate biomedical publications, to design the best research strategy to address a specific problem and to analyse data by appropriate statistical test selection. Multiple learner‐centred instructional methods and formative and summative assessments (written tasks, simulation exercises, portfolios and pre–post knowledge tests) were used to accomplish the learning outcomes. The analysis of the achievement of the group of students and a satisfaction survey for further feedback provided to the residents at the end of the curriculum were used for curriculum evaluation.

Results

All residents demonstrated competency at the end of the curriculum. The correct answer rate changed from 36.9% in the pre‐test to 79.8% in the post‐test. No common errors were detected in the rest of the assessment activities. All participants completed the questionnaire demonstrating high satisfaction for each independent category and with the overall educational programme, instruction and course in general.

Conclusions

The curriculum was validated by the assessment of students’ performance and a satisfaction survey, offering an example of a practical approach to the teaching of statistics to prepare students for a successful evidence‐based endodontic practice and lifelong learning education as practicing clinicians.