bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic procedures employed by dental practitioners in Australia with a focus on endodontic diagnostic procedures
Authors: Tan ASJ , Bennett GW , Tan JCW , Abbott PV
Published: March 2017

Background

An accurate diagnosis is the foundation for determining prognosis and appropriate management. This study adds to pre‐existing (albeit limited) evidence by exploring the use of diagnostic techniques amongst dental practitioners. The main aim of the study was to identify the availability, usage and clinician preference for specific diagnostic tests. A secondary aim was to investigate the use of diagnostic tests for common clinical scenarios.

Methods

A cross‐sectional survey was distributed online to dental practitioners registered with the Australian Dental Association. Quantitative data on clinician demography, and the availability and preference of diagnostic tests was summarized with Stata 13 software. Pearson's chi‐squared test was used to determine associations.

Results

General dental practitioners (GDP) and specialists comprised 86% and 14% of the 433 respondents, respectively. Unlike light transillumination, most GDP had radiography, biting tests and pulp sensibility tests available. The electric pulp test and ethyl chloride were first choices of most practitioners despite markedly lower availability relative to cold spray. Symptoms and endodontic assessments generally attracted wider usage of pulp testing.

Conclusions

More dental practitioners should utilize diagnostic testing in order to arrive at accurate diagnoses. The availability of diagnostic tests did not completely translate to usage and none of the scenarios presented warranted pulp sensibility testing from all respondents.
Changes to infant feeding guidelines: Relevance to dermatologists
Authors: Wong Celestine C , Allen Katrina J , Orchard David
Published: March 2017

The newly revised Australian Infant Feeding Guidelines recommends that all infants, including those at high risk of allergy, be introduced foods traditionally considered allergenic (such as peanut butter, dairy, wheat and egg) within the first year of life. High‐risk infants are those with early onset eczema (<3‐months old) or with moderate to severe eczema not responding to treatment (<6‐months old). Eczema can also represent a symptom of allergy presentation and the recommended introduction of some foods in this group may lead to allergic reactions at home. Although there have been no reported deaths from gradual food introduction to infants at home and cohort studies have only reported mild to moderate reactions, there is anecdotal evidence that more severe reactions can occur rarely. Allergic reactions, even if they are not life‐threatening, can be a terrifying experience for parents. Dermatologists play an important role when dealing with high‐risk infants in promoting the message of early allergenic food introduction yet also instigating appropriate allergy testing when necessary. This short review aims to provide an update to Australasian dermatologists on the newly revised Australian Infant Feeding Guidelines and provide a food allergy screening pathway for high‐risk infants prior to commencement of allergenic foods.
The Historical Roots of CIA‐Hollywood Propaganda
Authors: Redmond Pearse
Published: March 2017

The ability to use movies that tell persuasive stories is a powerful tool, particularly if it is consciously used to legitimize war, assassination, and illegal activities and to undermine the core principles of democracy. The U.S. Central Intelligence Agency (CIA) and the U.S. military have made use of that tool for almost a century, starting with the War Department's quiet support for the movieBirth of a Nationin 1915 and continuing for a century, including such recent CIA‐supported products asHomeland, The Agency, The Recruit, and many less likely movies and television shows. During World War II, this sort of propaganda was openly distributed, since there was a widespread consensus in support of that war. However, state‐sponsored propaganda in the form of Hollywood movies continued throughout the Cold War up to the present. The production of movies that completely distorted the political meaning of George Orwell's and Graham Greene's novels were important examples of this practice. CIA involvement was covert, since the target audience was the American public and the ideological perspective being propagated often ran counter to democratic ideals. This article recounts the history of the process by which Americans came to accept the ideas continuously promoted by the government, often without knowing that their favorite movies and television shows had been vetted or even altered by agents of the CIA or the Pentagon. Since these practices violate federal laws, the public at least has a right to know that we are being subjected to this sort of propaganda and how much tax money is spent to produce entertaining forms of disinformation.
The great opportunity of the andrological patient: cardiovascular and metabolic risk assessment and prevention
Authors: Foresta C. , Ferlin A. , Lenzi A. , Montorsi P. ,   Italian Study Group on Cardiometabolic Andrology
Published: March 2017

Andrologists, cardiologists and diabetologists (and general practitioners) have the great opportunity to collaborate and find shared clinical workup for the benefit of a large number of men. Several evidence established a link between erectile dysfunction (ED), cardiovascular disease (CVD), diabetes, and metabolic syndrome. Not only these conditions share many risk factors and pathophysiological mechanisms but also an emerging paradigm indicates that ED is, in fact, an independent marker of cardiovascular disease risk, CV events and CV mortality. However, there is no consensus on the best cardiologic investigation in men with ED with no known CVD and, on the contrary, on what is the clinical and prognostic role of detecting ED during cardiovascular investigation and CVD risk assessment. Only vasculogenic ED, which represents the most common type of organic ED, indeed represents a harbinger of CVD, especially for younger patients, and might be diagnosed by dynamic penile color doppler ultrasonography, which represents a real cardiovascular imaging technique that give evidence on the presence of systemic endothelial dysfunction and atherosclerosis. Furthermore, assessment of glucose and lipid metabolism is warranted as first step workup in all ED patients, and diabetologists should ask their patients for erectile function, address ED patients to andrologists, and consider vasculogenic ED in the context of the cardiovascular and metabolic workup and in the context of diabetic complications. Sexual symptoms (and testosterone levels) should sound as harbinger for cardiovascular and metabolic investigation and cardiologists and diabetologists have the opportunity to have a symptom (erectile dysfunction) and a vascular test (penile color doppler) that help them in better management of patients, their comorbidities and complications.
Serum from plasma rich in growth factors regenerates rabbit corneas by promoting cell proliferation, migration, differentiation, adhesion and limbal stemness
Authors: Etxebarria Jaime , Sanz‐Lázaro Sara , Hernáez‐Moya Raquel , Freire Vanesa , Durán Juan A. , Morales María–Celia , Andollo Noelia
Published: March 2017

Purpose

To evaluate the regenerating potential and the mechanisms through which the autologous serum derived from plasma rich in growth factors (s‐PRGF) favours corneal wound healing in vitro and in vivo.

Methods

We compared the effect of various concentrations of s‐PRGF versus fetal bovine serum (FBS) and control treatment in rabbit primary corneal epithelial and stromal cells and wounded rabbit corneas. Cell proliferation was measured using an enzymatic colorimetric assay. In vitro and in vivo wound‐healing progression was assessed by image‐analysis software. Migration and invasion were evaluated using transfilter assays. Histological structure was analysed in stained sections. Protein expression was evaluated by immunohistochemistry.

Results

s‐PRGF promoted the robust proliferation of epithelial cultures at any concentration, similar to FBS. Likewise, s‐PRGF and FBS produced similar re‐epithelialization rates in in vitro wound‐healing assays. In vivo, s‐PRGF treatment accelerated corneal wound healing in comparison with control treatment. This difference was significant only for 100% s‐PRGF treatment in our healthy rabbit model. Histological analysis confirmed normal epithelialization in all cases. Immunohistochemistry showed a higher expression of cytokeratins 3/76 and 15, zonula occludens‐1 and alpha‐smooth muscle actin proteins as a function of s‐PRGF concentration. Notably, keratocyte density in the anterior third of the stroma increased with increase in s‐PRGF concentration, suggesting an in vivo chemotactic effect of s‐PRGF on keratocytes that was further confirmed in vitro.

Conclusion

s‐PRGF promotes proliferation and migration and influences limbal stemness, adhesion and fibrosis during corneal healing.
Macular cystic changes as predictive factor for the recurrence of macular oedema in branch retinal vein occlusion
Authors: Tilgner Eric , Dalcegio Favretto Maiara , Tuisl Maria , Wiedemann Peter , Rehak Matus
Published: March 2017

Aim

To evaluate the role of small cystic macular changes as a prognostic factor for the recurrence of macular oedema (ME) in patients with branch retinal vein occlusion (BRVO) treated with anti‐VEGF drugs.

Methods

We performed retrospective chart analysis of 116 patients treated with intravitreal injection of ranibizumab (IVR) or bevacizumab (IVB) for ME secondary to BRVO. At the baseline and monthly follow‐up visits over a period of 12 months, a comprehensive ophthalmologic examination including best‐corrected visual acuity (BCVA) and volume scan of macula using Spectral domain optical coherence tomography (SD‐OCT) were performed. Patients without ME (CRT <250 μm) were screened for the presence of intraretinal cysts. In these patients, the changes in BCVA and CRT were evaluated over a period of 12 months and compared with the baseline.

Results

In the IVR group (41 patients), 91 events of macular cysts, without a worsening of BCVA, were detected by OCT. In 89 of 91 events (97%), BCVA and CRT deteriorated significantly (p < 0.0001) within the next 4–11 (in mean 7.1 ± 2.0) weeks. BCVA decreased from 0.38 ± 0.25 to 0.49 ± 0.27 logMAR and CRT increased significantly from 223 ± 43 to 605 ± 244 μm. In the IVB group (19 patients), 54 events of cystic changes were detected. All of these patients showed significant worsening of BCVA from 0.40 ± 0.19 to 0.57 ± 0.22 logMAR and CRT from 251 ± 17 to 490 ± 147 μm within 4–10 (in mean 7.8 ± 2.8) weeks after the first presence of small macular cysts.

Conclusion

In BRVO patients treated with anti‐VEGF drugs, the macular cystic changes may be used as an early indicator for impending recurrence of ME, with the decrease in BCVA in the following weeks. These patients should be scheduled for a next visit within 6–8 weeks.
Role and impact of the extracellular matrix on integrin‐mediated pancreatic β‐cell functions
Authors: Arous Caroline , Wehrle‐Haller Bernhard
Published: March 2017

Understanding the organisation and role of the extracellular matrix (ECM) in islets of Langerhans is critical for maintaining pancreatic β‐cells, and to recognise and revert the physiopathology of diabetes. Indeed, integrin‐mediated adhesion signalling in response to the pancreatic ECM plays crucial roles in β‐cell survival and insulin secretion, two major functions, which are affected in diabetes. Here, we would like to present an update on the major components of the pancreatic ECM, their role during integrin‐mediated cell‐matrix adhesions and how they are affected during diabetes. To treat diabetes, a promising approach consists in replacing β‐cells by transplantation. However, efficiency is low, because β‐cells suffer of anoikis, due to enzymatic digestion of the pancreatic ECM, which affects the survival of insulin‐secreting β‐cells. The strategy of adding ECM components during transplantation, to reproduce the pancreatic microenvironment, is a challenging task, as many of the regulatory mechanisms that control ECM deposition and turnover are not sufficiently understood. A better comprehension of the impact of the ECM on the adhesion and integrin‐dependent signalling in β‐cells is primordial to improve the healthy state of islets to prevent the onset of diabetes as well as for enhancing the efficiency of the islet transplantation therapy.
Cytokine biomarkers to predict antitumor responses to nivolumab suggested in a phase 2 study for advanced melanoma
Authors: Yamazaki Naoya , Kiyohara Yoshio , Uhara Hisashi , Iizuka Hajime , Uehara Jiro , Otsuka Fujio , Fujisawa Yasuhiro , Takenouchi Tatsuya , Isei Taiki , Iwatsuki Keiji , Uchi Hiroshi , Ihn Hironobu , Minami Hironobu , Tahara Hideaki
Published: March 2017

Promising antitumor activities of nivolumab, a fully humanized IgG4 inhibitor antibody against the programmed death‐1 protein, were suggested in previous phase 1 studies. The present phase 2, single‐arm study (JAPIC‐CTI #111681) evaluated the antitumor activities of nivolumab and explored its predictive correlates in advanced melanoma patients at 11 sites in Japan. Intravenous nivolumab 2 mg/kg was given repeatedly at 3‐week intervals to 35 of 37 patients enrolled from December 2011 to May 2012 until they experienced unacceptable toxicity, disease progression, or complete response. Primary endpoint was objective response rate. Serum levels of immune modulators were assessed at multiple time points. As of 21 October 2014, median response duration, median progression‐free survival, and median overall survival were 463 days, 169 days, and 18.0 months, respectively. The overall response rate and 1‐ and 2‐year survival rates were 28.6%, 54.3%, and 42.9%, respectively. Thirteen patients remained alive at the end of the observation period and no deaths were drug related. Grade 3–4 drug‐related adverse events were observed in 31.4% of patients. Pretreatment serum interferon‐γ, and interleukin‐6 and ‐10 levels were significantly higher in the patients with objective tumor responses than in those with tumor progression. In conclusion, giving repeated i.v. nivolumab had potent and durable antitumor effects and a manageable safety profile in advanced melanoma patients, strongly suggesting the usefulness of nivolumab for advanced melanoma and the usefulness of pretreatment serum cytokine profiles as correlates for predicting treatment efficacy.
Prognostic value of programmed death‐ligand 1 expression in patients with stage III colorectal cancer
Authors: Koganemaru Shigehiro , Inoshita Naoko , Miura Yuji , Miyama Yu , Fukui Yudai , Ozaki Yukinori , Tomizawa Kenji , Hanaoka Yutaka , Toda Shigeo , Suyama Koichi , Tanabe Yuko , Moriyama Jin , Fujii Takeshi , Matoba Shuichiro , Kuroyanagi Hiroya , Takano Toshimi
Published: March 2017

The programmed death‐1/programmed death‐ligand 1 (PD‐L1) pathway is a negative feedback pathway that suppresses the activity of T cells. Previous studies reported that high PD‐L1 expression on tumor cells (TC) was associated with poor survival in patients with colorectal cancer; however, the prognostic evaluation of these studies was limited because they included patients at various disease stages. The purpose of the present study was to evaluate the relationship between PD‐L1 status in the immune microenvironment and the clinicopathological features of stage III colorectal cancer. Two hundred and thirty‐five patients were included in the analysis. PD‐L1 expression on TC and tumor‐infiltrating mononuclear cells (TIMC) was evaluated by immunohistochemistry. The median follow‐up of thisi study was 52.9 months. A total of 8.1% of stage III colorectal cancer showed high PD‐L1 expression on TC and 15.3% showed high PD‐L1 expression on TIMC. Patients with high PD‐L1 expression on TC had significantly shorter disease‐free survival (DFS) than patients with low expression (hazard ratio [HR] 2.36; 95% confidence interval [CI], 1.21–4.62; P = 0.012). In addition, patients with high PD‐L1 expression on TIMC were associated with longer DFS than patients with low expression (HR 0.40; 95% CI, 0.16–0.98; P = 0.046). These findings suggest that PD‐L1 expression status may be a new predictor of recurrence for stage III colorectal cancer patients and highlight the necessity of evaluating PD‐L1 expression on TC and TIMC separately in the tumor microenvironment.
Integrated functions of membrane‐type 1 matrix metalloproteinase in regulating cancer malignancy: Beyond a proteinase
Authors: Sakamoto Takeharu , Seiki Motoharu
Published: March 2017

Membrane‐type 1 matrix metalloproteinase (MT1‐MMP) is expressed in different types of invasive and proliferative cells, including cancer cells and stromal cells. MT1‐MMP cleaves extracellular matrix proteins, membrane proteins and other pericellular proteins, thereby changing the cellular microenvironment and regulating signal activation. Critical roles of protease activity in cancer cell proliferation, invasion and metastasis have been demonstrated by many groups. MT1‐MMP also has a non‐protease activity in that it inhibits the oxygen‐dependent suppression of hypoxia‐inducible factors (HIFs) via Munc18‐1‐interacting protein 3 (Mint3) and thereby enhances the expression of HIF target genes. Elevated HIF activity in MT1‐MMP‐expressing cancer cells is a fundamental mechanism underlying the Warburg effect, a well‐known phenomenon where malignant cancer cells exhibit a higher rate of glucose metabolism. Because specific intervention of HIF activation by MT1‐MMP suppresses tumor formation by cancer cells in mice, both the proteolytic and non‐proteolytic activities of MT1‐MMP are important for tumor malignancy and function in an integrated manner. In this review, we summarize recent findings relating to how MT1‐MMP activates HIF and its effects on cancer cells and stromal cells.
Design, synthesis, and in vitro antituberculosis activity of benzo[6,7]cyclohepta[1,2‐b]pyridine‐1,3,4‐oxadiazole derivatives
Authors: Sajja Yasodakrishna , Vanguru Sowmya , Vulupala Hanmanth Reddy , Nagarapu Lingaiah , Perumal Yogeswari , Sriram Dharmarajan , Nanubolu Jagadeesh Babu
Published: March 2017

A new antitubercular agents, benzo[6,7]cyclohepta[1,2‐b]pyridine‐1,3,4‐ oxadiazole hybrids (6a–o), have been designed and synthesized involving oxidative cyclization of hydrazones by use of di(acetoxy)iodobenzene, characterized by IR,1H NMR,13C NMR, and HRMS, and further confirmed by X‐ray analysis. All the newly synthesized compounds 4a–o evaluated for their in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv (ATCC27294). Among the compounds tested, the compounds 4o (MIC: 1.56 μg/ml) and 4l, 4m (MIC: 3.125 μg/ml) are promising lead analogues and have shown lower cytotoxicity.
Modified benzoxazolone derivative as 18‐kDa TSPO ligand
Authors: Kumari Neelam , Chadha Nidhi , Srivastava Pooja , Mishra Lokesh Chandra , Bhagat Sunita , Mishra Anil K. , Tiwari Anjani K.
Published: March 2017

We have synthesized six new congeners of acetamidobenzoxazolone for Translocator Protein [18 kDa, TSPO] imaging. The best in vitro binding affinity (10.8 ± 1.2 nm) for TSPO was found for N‐methyl‐2‐(5‐(naphthalen‐1‐yl)‐2‐oxobenzo[d]oxazol‐3(2H)‐yl)‐N‐phenylacetamide, (NBMP). NBMP was synthesised by Suzuki coupling reaction between 2‐(5‐bromo‐2‐oxo‐1,3‐benzoxazol‐3(2H)‐yl)‐N‐phenylacetamide and napthalene‐1‐boronic acid. Computational docking and simulation studies showed not much impact of intersubject variability on binding which is one of the major drawbacks of several TSPO ligands. These findings suggested that NBMP may become a promising marker for visualization of neuroinflammation via TSPO targeting.
Clinical and mutation analysis of 24 Chinese patients with ornithine transcarbamylase deficiency
Authors: Shao Y. , Jiang M. , Lin Y. , Mei H. , Zhang W. , Cai Y. , Su X. , Hu H. , Li X. , Liu L.
Published: March 2017

The principal aim of this study was to examine the clinical manifestations, biochemical features, and molecular genetic characteristics of Chinese patients with ornithine transcarbamylase deficiency (OTCD) at a single medical center. We retrospectively analyzed 24 patients (17 males and 7 females) diagnosed with OTCD between 2006 and 2015. Five male patients had a neonatal presentation; 12 male patients had late onset disease and 7 female patients presented as symptomatic. Patients with a neonatal presentation had the highest peak plasma ammonia and glutamine levels at diagnosis with a high mortality (80% vs 16% in late onset disease). Most of the male late onset disease cases displayed neurologic damage with a mild elevation in plasma ammonia, and a significant increase in serum glutamine, which was commonly misdiagnosed as intracranial infection. In the symptomatic female group, mortality was abnormally high in China with some patients dying at the time of presentation during the first episode of hyperammonemia. Refractory hyperammonemia, serious hepatic function damage, recurrent infection and lethal mutation are the main reasons for poor clinical outcomes of the symptomatic females. Molecular analyses identified 19 different mutations, including 3 novel mutations (c.103insA, c.591C>A and c.805G>A).
A clinical tool to calculate post‐transplant survival using pre‐transplant clinical characteristics in adults with cystic fibrosis
Authors: Stephenson Anne L. , Sykes Jenna , Berthiaume Yves , Singer Lianne G. , Chaparro Cecilia , Aaron Shawn D. , Whitmore George Alex , Stanojevic Sanja
Published: March 2017

Background

We previously identified factors associated with a greater risk of death post‐transplant. The purpose of this study was to develop a clinical tool to estimate the risk of death after transplant based on pre‐transplant variables.

Methods

We utilized the Canadian CF registry to develop a nomogram that incorporates pre‐transplant clinical measures to assess post‐lung transplant survival. The 1‐, 3‐, and 5‐year survival estimates were calculated using Cox proportional hazards models.

Results

Between 1988 and 2012, 539 adult Canadians with CF received a lung transplant with 208 deaths in the study period. Four pre‐transplant factors most predictive of poor post‐transplant survival were older age at transplantation, infection with B. cepacia complex, low FEV1 percent predicted, and pancreatic sufficiency. A nonlinear relationship was found between risk of death and FEV1 percent predicted, age at transplant, and BMI. We constructed a risk calculator based on our model to estimate the 1‐, 3‐, and 5‐year probability of survival after transplant which is available online.

Conclusions

Our risk calculator quantifies the risk of death associated with lung transplant using pre‐transplant factors. This tool could aid clinicians and patients in the decision‐making process and provide information regarding the timing of lung transplantation.
Can Grassroots Mobilization of the Poorest Reduce Corruption? A Tale of Governance Reforms and Struggle against Petty Corruption in Bihar, India
Authors: Verma Rajiv , Gupta Saurabh , Birner Regina
Published: March 2017

The rural poor in India have long experienced corruption, exclusion from welfare schemes and the denial of rights. Critical accounts of development policy and practice advocate the need for pro‐poor governance reforms as well as effective mobilization of the poor for exercising their rights and entitlements. However, there is a dearth of empirical work which examines the following questions. What are the dynamics of such mobilization strategies in the environment of pro‐poor governance reforms? How do they affect local power relations from the perspective of the poorest social groups? And what are the challenges involved in sustaining struggles led by civil society organizations on behalf of the poorest and against petty corruption? This article addresses these questions in the context of a grassroots mobilization of Musahars (a Dalit caste group) in Bihar, one of the poorest provinces in India, which has recently initiated pro‐poor governance reforms. It explains what has or hasn't worked (and why) for the Musahars, in terms of their dealings with public officials. The authors argue that pro‐poor governance reforms and welfare schemes on their own are not sufficient; both grassroots mobilization and political will of the ruling dispensation are also necessary.
Comparative adherence to diabetes drugs: An analysis of electronic health records and claims data
Authors: Flory James , Gerhard Tobias , Stempniewicz Nikita , Keating Scott , Rowan Christopher G.
Published: March 2017

Non‐adherence to medications is a major challenge in diabetes care. The objective of this brief report is to compare adherence rates for 6 major classes of diabetes medications: metformin, sulfonylurea, thiazolidinedione, basal insulin, DPP‐4 inhibitors, and GLP‐1 receptor agonists. We used a data source that linked electronic prescriptions with insurance claims to assess whether new electronic prescriptions for diabetes medications were followed by dispensing claims consistent with that prescription. After one year of follow‐up, the daily medication possession probability (MPP) ‐ a measure of overall adherence ‐ at one year for sulfonylurea was 0.49 and for metformin was 0.46. Thiazolidinediones and basal insulin had a similar final daily MPP at 0.36 and 0.39, respectively, which was significantly lower than that for sulfonylurea or metformin (P < .05). GLP‐1 receptor agonists and DPP‐4 inhibitors were also comparable to one another at a final daily MPP of .30 and .21, respectively (P < .05 compared to any of the aforementioned drug classes). In summary, the rates at which diabetes drugs are prescribed, and the rates at which patients actually take them, differ substantially. Physicians should be aware of potentially significant challenges concerning adherence to newer agents.
Cardiac CT angiography in the emergency room: Apical hypertrophic cardiomyopathy presenting as acute coronary syndrome
Authors: Turner Michael C. , Kerut Edmund K. , Mckinnie James , Davis Michael , Hinton Christine
Published: March 2017

A 59‐year‐old male presented to the emergency room with symptoms of chest tightness and palpitations. Following conversion of atrial fibrillation to sinus rhythm, he had deep symmetrical T‐wave changes on his electrocardiogram. Symptoms resolved almost immediately, and his initial troponin was negative. He underwent cardiac CT angiography utilizing an emergency room triage protocol which resulted in a diagnosis of nonobstructive coronary artery disease and apical hypertrophic cardiomyopathy. Following a hospital stay of less than 24 hours, he was discharged to outpatient follow‐up on medical management and has remained asymptomatic over 6 months. This case presentation illustrates an example of the diversity of pathology that presents in emergency rooms with symptoms consistent with acute coronary syndrome.
Accounting for failures to reform in the Arab world
Authors: Commander Simon
Published: March 2017

Arab regimes have struggled to reform effectively and, as a consequence, have continued to perform poorly in terms of output and employment growth. Some Arab autocracies have experimented with partial liberalization, yielding benefits mainly for connected parties or cronies. There has been a chronic inability to craft policies capable of commanding widespread support in the population. Instead, the main groups in the economy have coalesced around the preservation of rents at the cost of achieving wider benefits. The paper attributes this not only to a combination of lack of credibility as well as issues of time consistency, but also to the failure to develop and present a coherent case for reforms capable of conferring benefits on the wider population, rather than concentrated benefits for a few.
Investigating movement in the laboratory: dispersal apparatus designs and the red flour beetle, Tribolium castaneum
Authors: Arnold Pieter A. , Rafter Michelle A. , Malekpour Rokhsareh , Cassey Phillip , Walter Gimme H. , White Craig R.
Published: March 2017

The natural dispersal of Tribolium castaneum Herbst (Coleoptera: Tenebrionidae) has been emulated in the laboratory for more than 50 years, using a simple dispersal apparatus. This has typically comprised of a starting container (initial resource or patch) connected by tubing, which contains thread for the animals to climb into a tube and hence to an end container. That is, beetles move to a new viable resource or patch from an inter‐patch zone or non‐viable habitat. We modified this basic apparatus design to test the effect of tubing length and tubing insertion angle on the dispersal rate and proportion of successful dispersers. We expected that the proportion of successful dispersers would be repeatable within each apparatus design, and that increasing tubing length and steepness of the insertion angle would reduce dispersal rate and success across apparatus designs. Dispersal increased linearly through time, similarly so for both males and females. The design with the most vertical tubing insertion angle had a lower proportion of successful dispersers. Tubing length also had a negative relationship with dispersal success (as judged by insects reaching the end container), but a significant reduction in dispersal success was only apparent between the shortest and longest tubing between containers. We suggest that locating and climbing the vertical section of string before they can enter the tubing between containers restricts dispersal and that at higher densities, insects exhibit greater inclination to climb. This type of apparatus has flexible design tolerances and further potential to study the dispersal of other small insect species that primarily use pedestrian locomotion.
Seasonality, floods and droughts structure larval fish assemblages in prairie rivers
Authors: Garcia Crystal , Schumann David A. , Howell Jessica , Graeb Brian D.S. , Bertrand Katie N. , Klumb Robert A.
Published: March 2017

Prairie stream fish assemblages experience seasonal shifts in habitat conditions, often coupled with powerful disturbance regimes, where systems fluctuate widely between drought and deluge. These abiotic drivers, more often than biotic factors, structure fish assemblages. Scouring floods may reset stream communities to early successional seres, and droughts may progressively eliminate species from communities. Therefore, fish assemblage structure resilience depends on recolonisation and reproductive success following a disturbance. Many plains fishes have life history traits that facilitate the wide dispersal and immediate contribution of offspring following disturbance events. However, descriptions of temporal and spatial patterns in larval assemblage structure in prairie streams are scarce, and few studies evaluate the effect of disturbances on reproduction. The objectives of this research were to (i) study the timing and contribution of native prairie stream fishes to drifting larval fish assemblages in three eastern South Dakota basins (Vermillion, James and Big Sioux) and (ii) describe larval fish responses to floods in the James River. We sampled drifting larval fish diversity during the spawning season from 2010 to 2012 throughout each basin. We also examined the effect of flooding on larval fish assemblage structure using data collected near the confluence of the James and Missouri rivers during baseflow (2003, 2004 and 2012) and flood conditions (2010). Subtle variability in spawning traits of prairie fishes and an apparent seasonal progression of larval fish taxa that secondarily respond to disturbance regimes suggests reproductive efforts are adapted to maximise the potential for successful recruitment in these severe systems.
Power politics and princely debts: why Germany's common currency failed, 1549–56†
Authors: Volckart Oliver
Published: March 2017

Using new sources, this article examines how in the years around 1550 Charles V and the imperial estates came close to creating a common currency for the Holy Roman Empire. The article analyses whose interests prevailed in the negotiations and how, despite the resistance of some important actors, the Imperial diet of 1551 was able to unanimously agree on the currency bill. It also analyses why the common currency still failed: This was the case because of the desire of many princes to ease the repayment of their debts by establishing a bimetallic currency, and even more importantly because of Charles V's attempt to weaken the Elector of Saxony by undervaluing the taler. In this, Charles exploited the diet's implicit ex‐ante agreement with him to set the rates at which old money was allowed to continue in circulation. His manipulations provoked resistance, raised the costs of implementing the common currency, and caused its failure.
Are data collected to support farm management suitable for monitoring soil indicators at the national scale?
Authors: Rawlins B. G. , Marchant B. , Stevenson S. , Wilmer W.
Published: March 2017

Monitoring of topsoil properties (referred to as indicators) at the national scale has been limited in general to government‐funded representative surveys. We consider a cost‐effective complementary source of soil information for monitoring agricultural soil across England and Wales (E&W): soil measurements paid for by farmers that we refer to as farmers' data (FD). A potential problem in using FD for soil monitoring is any unattributable sources of bias, such as the sample design. Farmers may choose to focus their measurements (purposively) where they perceive a particular problem. Such a source of bias is avoided in the random sampling adopted by statistically designed surveys, such as the Countryside Survey (CS2007) and LUCAS (Land Use/Cover Area frame statistical Survey). We used measurements from 143 000 FD soil samples from a single laboratory to estimate national mean values and confidence intervals of five topsoil indicators (pH, available P (Olsen), K, Mg and organic matter (OM)) across three combinations of nation (England or Wales) and land use (arable and horticulture (A&H) or improved grassland (IG)). We computed mean estimates for FD over two time periods (2004–9 and 2010–2105) and assessed the significance of any change. We compared these estimates with those from representative national surveys to establish whether there was evidence for bias and whether it could be explained. Mean estimates of topsoil pH for the FD and the LUCAS survey (same analytical method) were consistent for both A&H and IG. Although FD estimates of mean Olsen P (OP) concentrations were similar to previous surveys, we show it is likely that the larger mean OP concentrations observed in the LUCAS survey compared with FD for arable topsoil in England are partly due to an attributable source of analytical bias. For such quantifiable sources of bias, it might be possible to adjust estimated mean values from FD. However, FD might also include sources of unattributable bias, such as the effect of purposive sampling. It is important that contemporaneous data from surveys with statistically unbiased designs are available so that we can assess whether unattributable sources exert a significant effect over estimates of mean values computed from FD.

Highlights

Assessment of farmers' data (FD) to provide a potentially cost‐effective way to monitor topsoil indicators.

Few studies have compared national‐scale estimates of topsoil indicators with survey data from statistically unbiased designs and FD.

Bias between mean estimates from national surveys and FD could be accounted for.

The denser sampling of FD enables mapping of national survey data with greater accuracy.
MRI‐negative temporal lobe epilepsy—What do we know?
Authors: Muhlhofer Wolfgang , Tan Yee‐Leng , Mueller Susanne G. , Knowlton Robert
Published: March 2017

Temporal lobe epilepsy (TLE) is the most common focal epilepsy in adults. TLE has a high chance of becoming medically refractory, and as such, is frequently considered for further evaluation and surgical intervention. Up to 30% of TLE cases, however, can have normal (“nonlesional” or negative) magnetic resonance imaging (MRI) results, which complicates the presurgical workup and has been associated with worse surgical outcomes. Helped by contributions from advanced imaging techniques and electrical source localization, the number of surgeries performed on MRI‐negative TLE has increased over the last decade. Thereby new epidemiologic, clinical, electrophysiologic, neuropathologic, and surgical data of MRI‐negative TLE has emerged, showing characteristics that are distinct from those of lesional TLE. This review article summarizes what we know today about MRI‐negative TLE, and discusses the comprehensive assessment of patients with MRI‐negative TLE in a structured and systematic approach. It also includes a concise description of the most recent developments in structural and functional imaging, and highlights postprocessing imaging techniques that have been shown to add localization value in MRI‐negative epilepsies. We evaluate surgical outcomes of MRI‐negative TLE, identify prognostic makers of postoperative seizure freedom, and discuss strategies for optimizing the selection of surgical candidates in this group.
The how, why and clinical importance of stratum corneum acidification
Authors: Elias Peter M.
Published: March 2017

In this article, I review the multiple endogenous mechanisms that contribute to the highly acidic pH of normal stratum corneum (SC). Then, I describe how each mechanism potentially impacts specific defensive functions of the SC. Finally, I review the rapidly expanding, clinical implications and potential therapeutic applications of SC acidification.
Signalling and targeted therapy of inflammatory cells in epidermolysis bullosa acquisita
Authors: Ludwig Ralf J.
Published: March 2017

Pemphigoid diseases (PDs) are chronic and life‐threatening autoimmune diseases of the skin and mucous membranes. PDs are characterized and caused by autoantibodies targeting components of the basement membrane. In the PD epidermolysis bullosa acquisita (EBA), the target autoantigen is type VII collagen. Current treatment options of PD, especially EBA, are limited and are mostly based on systemic immunosuppression. Animal models of PD have greatly advanced our understanding of PD pathogenesis. This has led to the identification of several novel therapeutic targets, including signalling molecules. Herein, the contribution of signalling molecules in the pathogenesis of the PD EBA and the effects of pharmacological targeting of these pathways are reviewed in detail. The p38 MAPK, ERK1/2, AKT, PI3Kβ, Hsp90, RORα, PDE4, Src kinases and CARD9 have been demonstrated to be critically involved in EBA pathogenesis. With the advent of new signal transduction inhibitors, we expect that the so far poor prognosis of EBA and other PD will improve significantly in the future.
The hair follicle enigma
Authors: Bernard Bruno A.
Published: March 2017

The hair follicle is a mini‐organ endowed with a unique structure and cyclic behaviour. Despite the intense research efforts which have been devoted at deciphering the hair follicle biology over the past 70 years, one must admit that hair follicle remains an enigma. In this brief review, various aspects of hair follicle biology will be addressed, and more importantly, unsolved questions and new possible research tracks will be highlighted, including hair follicle glycobiology and exosome‐mediated cell‐cell interactions. Even though bricks of knowledge are solidly being acquired, an integrative picture remains to emerge. One can predict that computer science, algorithms and bioinformatics will assist in fostering our understanding hair biology.
Increased levels of circulating platelet‐derived microparticles are associated with metastatic cutaneous melanoma
Authors: Moreau Joséphine , Pelletier Fabien , Biichle Sabeha , Mourey Guillaume , Puyraveau Marc , Badet Nicolas , Caubet Matthieu , Laresche Claire , Garnache‐Ottou Francine , Saas Philippe , Seilles Estelle , Aubin François
Published: March 2017

We investigated the plasma levels of PMPs in patients with 45 stage III and 45 stage IV melanoma. PMPs were characterised by flow cytometry and their thrombogenic activity. We also investigated the link between PMPs circulating levels and tumor burden. The circulating levels of PMPs were significantly higher in stage IV (8500 μL−1) than in patients with stage III (2041 μL−1) melanoma (P=.0001). We calculated a highly specific (93.3%) and predictive (91.7%) cut‐off value (5311 μL−1) allowing the distinction between high‐risk stage III and metastatic stage IV melanoma. The thrombogenic activity of PMPs was significantly higher in patients with stage IV melanoma (clotting time: 40.7 second vs 65 second, P=.0001). There was no significant association between the radiological tumoral syndrome and the plasma level of PMPs. Our data suggest the role of PMPs in metastatic progression of melanoma.
Analysis of the skin of mice humanized for the immune system
Authors: Centlivre Mireille , Petit Maxime , Hutton Andrew J. , Dufossée Mélody , Boccara David , Mimoun Maurice , Soria Angèle , Combadière Béhazine
Published: March 2017

Development of new immunotherapeutic strategies relies on the ability to activate the right cells at the right place and at the right moment and on the capacity of these cells to home to the right organ(s). Skin delivery has shown high potency for immunotherapeutic administration. However, an adequate in vivo model of human skin immunity is still a critical bottleneck. We demonstrated here that the skin of human immune system mice is colonized by human hematopoietic cells, mainly human T cells and that complementation with human antigen‐presenting cells at the vaccination site allowed the induction of an immune response.
Effect of bucladesine, pentoxifylline, and H‐89 as cyclic adenosine monophosphate analog, phosphodiesterase, and protein kinase A inhibitor on acute pain
Authors: Salehi Forouz , Hosseini‐Zare Mahshid S. , Aghajani Haleh , Seyedi Seyedeh Yalda , Hosseini‐Zare Maryam S. , Sharifzadeh Mohammad
Published: March 2017

The aim of this study was to determine the effects of cyclic adenosine monophosphate (cAMP) and its dependent pathway on thermal nociception in a mouse model of acute pain. Here, we studied the effect of H‐89 (protein kinase A inhibitor), bucladesine (Db‐cAMP) (membrane‐permeable analog of cAMP), and pentoxifylline (PTX; nonspecific phosphodiesterase (PDE) inhibitor) on pain sensation. Different doses of H‐89 (0.05, 0.1, and 0.5 mg/100 g), PTX (5, 10, and 20 mg/100 g), and Db‐cAMP (50, 100, and 300 nm/mouse) were administered intraperitoneally (I.p.) 15 min before a tail‐flick test. In combination groups, we injected the first and the second compounds 30 and 15 min before the tail‐flick test, respectively. I.p. administration of H‐89 and PTX significantly decreased the thermal‐induced pain sensation in their low applied doses. Db‐cAMP, however, decreased the pain sensation in a dose‐dependent manner. The highest applied dose of H‐89 (0.5 mg/100 g) attenuated the antinociceptive effect of Db‐cAMP in doses of 50 and 100 nm/mouse. Surprisingly, Db‐cAMP decreased the antinociceptive effect of the lowest dose of H‐89 (0.05 mg/100 g). All applied doses of PTX reduced the effect of 0.05 mg/100 g H‐89 on pain sensation; however, the highest dose of H‐89 compromised the antinociceptive effect of 20 mg/100 g dose of PTX. Co‐administration of Db‐cAMP and PTX increased the antinociceptive effect of each compound on thermal‐induced pain. In conclusion, PTX, H‐89, and Db‐cAMP affect the thermal‐induced pain by probably interacting with intracellular cAMP and cGMP signaling pathways and cyclic nucleotide‐dependent protein kinases.
Arctic shrub growth trajectories differ across soil moisture levels
Authors: Ackerman Daniel , Griffin Daniel , Hobbie Sarah E. , Finlay Jacques C.
Published: March 2017

The circumpolar expansion of woody deciduous shrubs in arctic tundra alters key ecosystem properties including carbon balance and hydrology. However, landscape‐scale patterns and drivers of shrub expansion remain poorly understood, inhibiting accurate incorporation of shrub effects into climate models. Here, we use dendroecology to elucidate the role of soil moisture in modifying the relationship between climate and growth for a dominant deciduous shrub, Salix pulchra, on the North Slope of Alaska, USA. We improve upon previous modeling approaches by using ecological theory to guide model selection for the relationship between climate and shrub growth. Finally, we present novel dendroecology‐based estimates of shrub biomass change under a future climate regime, made possible by recently developed shrub allometry models. We find that S. pulchra growth has responded positively to mean June temperature over the past 2.5 decades at both a dry upland tundra site and an adjacent mesic riparian site. For the upland site, including a negative second‐order term in the climate–growth model significantly improved explanatory power, matching theoretical predictions of diminishing growth returns to increasing temperature. A first‐order linear model fit best at the riparian site, indicating consistent growth increases in response to sustained warming, possibly due to lack of temperature‐induced moisture limitation in mesic habitats. These contrasting results indicate that S. pulchra in mesic habitats may respond positively to a wider range of temperature increase than S. pulchra in dry habitats. Lastly, we estimate that a 2°C increase in current mean June temperature will yield a 19% increase in aboveground S. pulchra biomass at the upland site and a 36% increase at the riparian site. Our method of biomass estimation provides an important link toward incorporating dendroecology data into coupled vegetation and climate models.
Counting invasive breast cancer cells in the HER2 silver in‐situ hybridization test: how many cells are enough?
Authors: Polónia António , Eloy Catarina , Pinto João , Braga Ana Costa , Oliveira Guilherme , Schmitt Fernando
Published: March 2017

Aim

To evaluate the intraobserver and interobserver reproducibility of the HER2 in‐situ hybridization (ISH) test in breast cancer by measuring the impact of counting different numbers of invasive cancer cells.

Methods and results

A cohort of 101 primary invasive breast cancer cases were evaluated for HER2 gene amplification by silver ISH, and the concordance among four observers with different levels of experience, counting different numbers of invasive cancer cells, was determined. The evaluation of the samples included scoring 20 nuclei, in three different areas. The cases were scored twice, with a washout interval of at least 2 weeks. We observed an increase in the intraobserver concordance rate between the first and second evaluations with an increase in cell count. A count of 60 invasive cells was needed to obtain a concordance rate near 95% and an agreement rate greater than 0.80 by all observers. The interobserver concordance rate of the HER2 test also increased with the increase in cell count, reaching at least a 90% concordance rate with a count of 60 invasive cells. The median variability of both the HER2/CEP17 ratio and the average HER2 copy number between different evaluations decreased with the increase in cell count, being statistically higher in HER2‐positive cases.

Conclusions

The minimal cell number recommended in current guidelines should be raised to at least 40, and preferably 60, invasive cells. Moreover, cases with amplification levels close to the threshold should be subjected to a dual count from an experienced observer.