bluuebunny/crossref_metadata_2025 huggingface dataset:
DiskAccel
Authors: Tarihi Mojtaba , Asadi Hossein , Sarbazi-Azad Hamid
Published: June 2015

Disk traces are typically used to analyze real-life workloads and for replay-based evaluations. This approach benefits from capturing important details such as varying behavior patterns, bursty activity, and diurnal patterns of system activity, which are often missing from the behavior of workload synthesis tools. However, accurate capture of such details requires recording traces containing long durations of system activity, which are difficult to use for replay-based evaluation. One way of solving the problem of long storage trace duration is the use of disk simulators. While publicly available disk simulators can greatly accelerate experiments, they have not kept up with technological innovations in the field. The variety, complexity, and opaque nature of storage hardware make it very difficult to implement accurate simulators. The alternative, replaying the whole traces on real hardware, suffers from either long run-time or required manual reduction of experimental time, potentially at the cost of reduced accuracy. On the other hand, burstiness, auto-correlation, and complex spatio-temporal properties of storage workloads make the known methods of sampling workload traces less effective.

In this paper, we present a methodology called DiskAccel to efficiently select key intervals of a trace as representatives and to replay them to estimate the response time of the whole workload. Our methodology extracts a variety of spatial and temporal features from each interval and uses efficient data mining techniques to select the representative intervals. To verify the proposed methodology, we have implemented a tool capable of running whole traces or selective intervals on real hardware, warming up hardware state in an accelerated manner, and emulating request causality while minimizing request inter-arrival time error. Based on our experiments, DiskAccel manages to speed up disk replay by more than two orders of magnitude, while keeping average estimation error at 7.6%.
Impact of Fairness and Heterogeneity on Delays in Large-scale Content Delivery Networks
Authors: Shah Virag , de Veciana Gustavo
Published: June 2015

We consider multi-class queueing systems where the per class service rates depend on the network state, fairness criterion, and is constrained to be in a symmetric polymatroid capacity region. We develop new comparison results leading to explicit bounds on the mean service time under various fairness criteria and possibly heterogeneous loads. We then study large-scale systems with growing numbers of service classes
n
(e.g., files), heterogenous servers
m
and polymatroid capacity resulting from a random bipartite graph modeling service availability (e.g., placement of files across servers). This models, for example, a large scale content delivery network (CDN) supporting parallel servicing of a download request. For an appropriate asymptotic regime, we show that the system's capacity region is uniformly close to a symmetric polymatroid -- i.e., heterogeneity in servers' capacity and file placement disappears.

Combining our comparison results and the asymptotic 'symmetry' in large systems, we study performance robustness to heterogeneity in per class loads and fairness criteria. Roughly, if each class can be served by

c
n

= ω(log
n
) servers, the load per class does not exceed θ
n
=
o
(min(
n
/log
n
,

c
n

)), and average server utilization is bounded by λ < 1, then mean delay satisfies the following bound:
E
[
D
(n)
] ≤
K
θ
n
/

c
n

1/λ log (1/1--λ}\right), where
K
is a constant. Thus, large, randomly configured CDNs with a logarithmic number of file copies are robust to substantial load and server heterogeneities for a class of fairness criteria.
Distributed Proportional Fair Load Balancing in Heterogenous Systems
Authors: Yun Se-Young , Proutiere Alexandre
Published: June 2015

We consider the problem of distributed load balancing in heterogenous parallel server systems, where the service rate achieved by a user at a server depends on both the user and the server. Such heterogeneity typically arises in wireless networks (e.g., servers may represent frequency bands, and the service rate of a user varies across bands). We assume that each server equally shares in time its capacity among users allocated to it. Users initially attach to an arbitrary server, but at random instants of time, they probe the load at a new server and migrate there if this improves their service rate. The dynamics under this distributed load balancing scheme, referred to as Random Local Search (RLS), may be interpreted as those generated by strategic players updating their strategy in a load balancing game. In closed systems, where the user population is fixed, we show that this game has pure Nash Equilibriums (NEs), and that these equilibriums get close to a Proportionally Fair (PF) allocation of users to servers when the user population grows large. We provide an anytime upper bound of the gap between the allocation under RLS and the PF allocation. In open systems, where users randomly enter the system and leave upon service completion, we establish that the RLS algorithm stabilizes the system whenever this it at all possible under centralized load balancing schemes, i.e., it is throughput-optimal. The proof of this result relies on a novel Lyapounov analysis that captures the dynamics due to both users' migration and their arrivals and departures. To our knowledge, the RLS algorithm constitutes the first fully distributed and throughput-optimal load balancing scheme in heterogenous parallel server systems. We extend our analysis to various scenarios, e.g. to cases where users can be simultaneously served by several servers. Finally we illustrate through numerical experiments the efficiency of the RLS algorithm.
When Virtual Meets Physical at the Edge
Authors: Birke Robert , Björkqvist Mathias , Minkenberg Cyriel , Schmatz Martin , Chen Lydia Y.
Published: June 2015

The wide deployment of virtualization in datacenters catalyzes the emergence of virtual traffic that delivers the network demands between the physical network and the virtual machines hosting clients' services. Virtual traffic presents new opportunities for reducing physical network demands, as well as challenges of increasing management complexity. Given the plethora of prior art on virtualization technologies in datacenters, surprisingly little is still known about such virtual traffic, and its dependence on the physical network and virtual machines. This paper provides a multi-faceted analysis of the patterns and impacts of multiplexing the virtual traffic onto the physical network, particularly from the perspective of the network edge. We use a large collection of field data from production datacenters hosting a large number of diversified services from multiple enterprise tenants. Our first focus is on uncovering the temporal and spatial characteristics of the virtual and physical traffic, i.e., network demand growth and communication patterns, with special attention paid to the traffic of migrating virtual machines. The second focus is on characterizing the effect of network multiplexing in terms of communication locality, traffic load heterogeneity, and the dependency on CPU processing power at the edges of the network. Last but not least, we conduct a mirroring analysis on service QoS, defined by the service unavailability induced by network related issues, e.g., loads. We qualitatively and quantitatively discuss the implications and opportunities that virtual traffic presents for network capacity planning of virtualized networks and datacenters.
Memory Row Reuse Distance and its Role in Optimizing Application Performance
Authors: Kandemir Mahmut , Zhao Hui , Tang Xulong , Karakoy Mustafa
Published: June 2015

Continuously increasing dataset sizes of large-scale applications overwhelm on-chip cache capacities and make the performance of last-level caches (LLC) increasingly important. That is, in addition to maximizing LLC hit rates, it is becoming equally important to reduce LLC miss latencies. One of the critical factors that influence LLC miss latencies is row-buffer locality (i.e., the fraction of LLC misses that hit in the large buffer attached to a memory bank). While there has been a plethora of recent works on optimizing row-buffer performance, to our knowledge, there is no study that quantifies the full potential of row-buffer locality and impact of maximizing it on application performance.

Focusing on multithreaded applications, the first contribution of this paper is the definition of a new metric called (memory) row reuse distance (RRD). We show that, while intra-core RRDs are relatively small (increasing the chances for row-buffer hits), inter-core RRDs are quite large (increasing the chances for row-buffer misses). Motivated by this, we propose two schemes that measure the maximum potential benefits that could be obtained from minimizing RRDs, to the extent allowed by program dependencies. Specifically, one of our schemes (Scheme-I) targets only intra-core RRDs, whereas the other one (Scheme-II) aims at reducing both intra-core RRDs and inter-core RRDs. Our experimental evaluations demonstrate that (i) Scheme-I reduces intra-core RRDs but increases inter-core RRDs; (ii) Scheme-II reduces inter-core RRDs significantly while achieving a similar behavior to Scheme-I as far as intra-core RRDs are concerned; (iii) Scheme-I and Scheme-II improve execution times of our applications by 17% and 21%, respectively, on average; and (iv) both our schemes deliver consistently good results under different memory request scheduling policies.
Multi-Resource Fairness
Authors: Bonald Thomas , Roberts James
Published: June 2015

Designing efficient and fair algorithms for sharing multiple resources between heterogeneous demands is becoming increasingly important. Applications include compute clusters shared by multi-task jobs and routers equipped with middleboxes shared by flows of different types. We show that the currently preferred objective of Dominant Resource Fairness (DRF) has a significantly less favorable efficiency-fairness tradeoff than alternatives like Proportional Fairness and our proposal, Bottleneck Max Fairness. We propose practical algorithms to realize these sharing objectives and evaluate their performance under a stochastic demand model. It is shown, in particular, that the strategyproofness property that motivated the choice of DRF for an assumed fixed set of jobs or flows, is largely irrelevant when demand is dynamic.
Reliable Multiple-choice Iterative Algorithm for Crowdsourcing Systems
Authors: Lee Donghyeon , Kim Joonyoung , Lee Hyunmin , Jung Kyomin
Published: June 2015

The appearance of web-based crowdsourcing systems gives a promising solution to exploiting the wisdom of crowds efficiently in a short time with a relatively low budget. Despite their efficiency, crowdsourcing systems have an inherent problem in that responses from workers can be unreliable since workers are low-paid and have low responsibility. Although simple majority voting can be a solution, various research studies have sought to aggregate noisy responses to obtain greater reliability in results through effective techniques such as Expectation-Maximization (EM) based algorithms. While EM-based algorithms get the limelight in crowdsourcing systems due to their useful inference techniques, Karger et al. made a significant breakthrough by proposing a novel iterative algorithm based on the idea of low-rank matrix approximations and the message passing technique. They showed that the performance of their iterative algorithm is order-optimal, which outperforms majority voting and EM-based algorithms. However, their algorithm is not always applicable in practice since it can only be applied to binary-choice questions. Recently, they devised an inference algorithm for multi-class labeling, which splits each task into a bunch of binary-choice questions and exploits their existing algorithm. However, it has difficulty in combining into real crowdsourcing systems since it overexploits redundancy in that each split question should be queried in multiple times to obtain reliable results.

In this paper, we design an iterative algorithm to infer true answers for multiple-choice questions, which can be directly applied to real crowdsourcing systems. Our algorithm can also be applicable to short-answer questions as well. We analyze the performance of our algorithm, and prove that the error bound decays exponentially. Through extensive experiments, we verify that our algorithm outperforms majority voting and EM-based algorithm in accuracy.
MaxWeight Scheduling
Authors: Singh Rahul , Stolyar Alexander
Published: June 2015

The model is a "generalized switch", serving multiple traffic flows in discrete time. The switch uses MaxWeight algorithm to make a service decision (scheduling choice) at each time step, which determines the probability distribution of the amount of service that will be provided. We are primarily motivated by the following question: in the heavy traffic regime, when the switch load approaches critical level, will the service processes provided to each flow remain "smooth" (i.e., without large gaps in service)? Addressing this question reduces to the analysis of the asymptotic behavior of the unscaled queue-differential process in heavy traffic. We prove that the stationary regime of this process converges to that of a positive recurrent Markov chain, whose structure we explicitly describe. This in turn implies asymptotic "smoothness" of the service processes.
Detecting Sponsored Recommendations
Authors: Krishnasamy Subhashini , Sen Rajat , Oh Sewoong , Shakkottai Sanjay
Published: June 2015

Personalized recommender systems provide great opportunities for targeted advertisements, by displaying ads alongside genuine recommendations. We consider a
biased
recommendation system where such ads are displayed without any tags (disguised as genuine recommendations), rendering them indistinguishable to users. We consider the problem of detecting such a bias and propose an algorithm that uses statistical analysis based on binary feedback data from a subset of users. We prove that the proposed algorithm detects bias with high probability for a broad class of recommendation systems with sufficient number of feedback samples.
Clustering and Inference From Pairwise Comparisons
Authors: Wu Rui , Xu Jiaming , Srikant Rayadurgam , Massoulie Laurent , Lelarge Marc , Hajek Bruce
Published: June 2015

Given a set of pairwise comparisons, the classical ranking problem computes a single ranking that best represents the preferences of all users. In this paper, we study the problem of inferring individual preferences, arising in the context of making personalized recommendations. In particular, we assume users form clusters; users of the same cluster provide similar pairwise comparisons for the items according to the Bradley-Terry model. We propose an efficient algorithm to estimate the preference for each user: first, compute the
net-win
vector for each user using the comparisons; second, cluster the users based on the net-win vectors; third, estimate a single preference for each cluster separately. We show that the net-win vectors are much less noisy than the high dimensional vectors of pairwise comparisons, therefore our algorithm can cluster the users reliably. Moreover, we show that, when a cluster is only approximately correct, the maximum likelihood estimation for the Bradley-Terry model is still close to the true preference.
Detecting and Localizing End-to-End Performance Degradation for Cellular Data Services
Authors: Ahmed Faraz , Erman Jeffrey , Ge Zihui , Liu Alex X. , Wang Jia , Yan He
Published: June 2015

Nowadays mobile device (e.g., smartphone) users not only have a high expectation on the availability of the cellular data service, but also increasingly depend on the high end-to-end (E2E) performance of their applications. Since the E2E performance of individual application sessions may vary greatly, depending on factors such as the cellular network condition, the content provider, the type/model of the mobile devices, and the application software, detecting and localizing service performance degradations in a timely manner at large scale is of great value to cellular service providers. In this paper, we build a holistic measurement system that tracks session-level E2E performance metrics along with the service attributes for these factors. Using data collected from a major cellular service provider, we first model the expected E2E service performance with a regression based approach, detect performance degradation conditions based on the time series of fine-grained measurement data, and finally localize the service degradation using association-rule-mining techniques. Our deployment experience reveals that in 80% of the detected problem instances, performance degradation can be attributed to non-network-location specific factors, such as a common content provider, or a set of applications running on certain models of devices.
Lagrangian-based Online Stochastic Bin Packing
Authors: Gupta Varun , Radovanovic Ana
Published: June 2015

Motivated by the problem of packing Virtual Machines on physical servers in the cloud, we study the problem of online stochastic bin packing under two settings -- packing with permanent items, and packing under item departures. In the setting with permanent items, we present the first truly distribution-oblivious bin packing heuristic that achieves O(√
n
) regret compared to OPT for all distributions. Our algorithm is essentially gradient descent on suitably defined Lagrangian relaxation of the bin packing Linear Program. We also prove guarantees of our heuristic against non
i.i.d.
input using a randomly delayed Lyapunov function to smoothen the input.

For the setting where items eventually depart, we are interested in minimizing the steady-state number of bins. Our algorithm extends as is to the case of item departures. Further, leveraging the Lagrangian approach, we generalize our algorithm to a setting where the processing time of an item is inflated by a certain known factor depending on the configuration it is packed in.
A Simple Model to Quantify the Impact of Memory Latency and Bandwidth on Performance
Authors: Clapp Russell , Dimitrov Martin , Kumar Karthik , Viswanathan Vish , Willhalm Thomas
Published: June 2015

In recent years, DRAM technology improvements have scaled at a much slower pace than processors. While server processor core counts grow from 33% to 50% on a yearly cadence, DDR4 memory channel bandwidth has grown at a slower rate, and memory latency has remained relatively flat for some time. Meanwhile, new computing paradigms have emerged, which involve analyzing massive volumes of data in real time and place pressure on the memory subsystem. The combination of these trends makes it important for computer architects to understand the sensitivity of the workload performance to memory bandwidth and latency. In this paper, we outline and validate a methodology for quick and quantitative performance estimation using a real-world workload.
Bounds Implied by Drift with Applications
Authors: Hajek Bruce
Published: June 2015

A recurring theme in the design of control schemes for computer communication networks has been to identify the drift of critical quantities such as queue lengths, and then devise control strategies that close the loop. A useful tool for the performance analysis of such strategies are bounds on deviations from the expected trajectory. This talk identifies an incomplete list of such tools that have been used in a broad class of applications, for both stochastic and deterministically constrained models of load.
Amelioration of nonalcoholic fatty liver disease by hepatic stimulator substance via preservation of carnitine palmitoyl transferase-1 activity
Authors: Xiao Weichun , Ren Meng , Zhang Can , Li Shenglan , An Wei
Published: June 2015

Nonalcoholic steatohepatitis (NASH) is the progressive form of nonalcoholic fatty liver disease and so far is supposed to be related with mitochondrial impairment. Hepatic stimulator substance (HSS) has been defined as a liver-protective factor promoting hepatocyte DNA synthesis and hepatic proliferation after liver intoxication. We previously reported that HSS ameliorated hepatocyte death, probably because of its preservation of mitochondria. This study aims to explore whether HSS could protect carnitine palmitoyl transferase-1 (CPT-1), an essential enzyme responsible for β-oxidation of free fatty acids in mitochondria, from lipotoxicity, thus alleviating hepatic lipid deposition. To test this, the HSS gene was delivered into C57BL/6J mice and efficiently expressed in the liver. NASH mice were prepared with high-fat diet or methionine-choline-deficient diet. The results showed that hepatic inflammation and liver functions were alleviated in the HSS-transfected mice; meanwhile, the activity of CPT-1 was obviously protected. Moreover, oleic acid (OA) treatment resulted in remarkable lipid accumulation in HepG2 cells; this deposition was improved by HSS transfection. Simultaneously, the CPT-1 activity, which was impaired by OA treatment, was profoundly rescued in the HSS-expressing cells. CPT-1 activity was more severely impaired if the OA treatment was combined with S15176, a CPT-1 inhibitor. However, this impairment was effectively reduced by the HSS transfection, and the effect was enhanced by C75, a CPT-1 activator. Interestingly, if the cells were transfected with HSS-siRNA, the preservation of CPT-1 provided by HSS was again diminished. In conclusion, HSS reduces lipotoxicity to mitochondria most likely via preservation of CPT-1.
Fuel metabolism in Canada geese: effects of glucagon on glucose kinetics
Authors: Vaillancourt Eric , Weber Jean-Michel
Published: June 2015

During prolonged fasting, birds must rely on glucose mobilization to maintain normoglycemia. Glucagon is known to modulate avian energy metabolism during prolonged fasting, but the metabolic effects of this hormone on long-distance migrant birds have never been investigated. Our goal was to determine whether glucagon regulates the mobilization of the main lipid and carbohydrate fuels in migrant birds. Using the Canada goose ( Branta canadensis) as a model species, we looked for evidence of fuel mobilization via changes in metabolite concentrations. No changes could be found for any lipid fraction, but glucagon elicited a strong increase in glucose concentration. Therefore, we aimed to quantify the effects of this hormone on glucose kinetics using continuous infusion of 6-[3H]-d-glucose. Glucagon was found to cause a 50% increase in glucose mobilization (from 22.2 ± 2.4 μmol·kg−1·min−1to 33.5 ± 3.3 μmol·kg−1·min−1) and, together with an unchanged rate of carbohydrate oxidation, led to a 90% increase in plasma glucose concentration. This hormone also led to a twofold increase in plasma lactate concentration. No changes in plasma lipid concentration or composition were observed. This study is the first to demonstrate how glucagon modulates glucose kinetics in a long-distance migrant bird and to quantify its rates of glucose mobilization.
Degradation of extracellular chondroitin sulfate delays recovery of network activity after perturbation
Authors: Hudson Amber E. , Gollnick Clare , Gourdine Jean-Philippe , Prinz Astrid A.
Published: June 2015

Chondroitin sulfate proteoglycans (CSPGs) are widely studied in vertebrate systems and are known to play a key role in development, plasticity, and regulation of cortical circuitry. The mechanistic details of this role are still elusive, but increasingly central to the investigation is the homeostatic balance between network excitation and inhibition. Studying a simpler neuronal circuit may prove advantageous for discovering the mechanistic details of the cellular effects of CSPGs. In this study we used a well-established model of homeostatic change after injury in the crab Cancer borealis to show first evidence that CSPGs are necessary for network activity homeostasis. We degraded CSPGs in the pyloric circuit of the stomatogastric ganglion with the enzyme chondroitinase ABC (chABC) and found that removal of CSPGs does not influence the ongoing rhythm of the pyloric circuit but does limit its capacity for recovery after a networkwide perturbation. Without CSPGs, the postperturbation rhythm is slower than in controls and rhythm recovery is delayed. In addition to providing a new model system for the study of CSPGs, this study suggests a wider role for CSPGs, and perhaps the extracellular matrix in general, beyond simply plastic reorganization (as observed in mammals) and into a foundational regulatory role of neural circuitry.
ControllingListeria monocytogenesScott A on Surfaces of Fully Cooked Turkey Deli Product Using Organic Acid-Containing Marinades as Postlethality Dips
Authors: Casco Gerardo , Johnson Jennifer L. , Taylor T. Matthew , Gaytán Carlos N. , Brashears Mindy M. , Alvarado Christine Z.
Published: June 2015

This study evaluated the efficacy of organic acids applied singly or in combination as postlethality dips to sliced uncured turkey deli loaves to inhibit the growth ofListeria monocytogenes(Lm) Scott A. Treatments consisted of sodium lactate (SL; 3.6%), potassium lactate (PL; 3.6%), sodium citrate (SC; 0.75%), a combination of SL and sodium diacetate (SDA; 0.25%), and a combination of SL/PL/SDA, alongside appropriate negative and positive controls. Products were inoculated with 104–105 CFU/mL streptomycin-resistant (1500 μg/mL) Lm Scott A prior to treatment. Products were then stored at ~4°C and sampled at 0, 7, 14, 21, 28, 42, and 56 d. The SL/SDA combination applied to turkey slices extended the lag phase through 21 days of refrigerated storage. Numbers of Lm Scott A rose by 0.7 log10 CFU/g through the 56 d storage period. The application of the SL/PL/SDA treatment to turkey product surfaces extended the lag phase through 42 d, with pathogen numbers declining after 21 d. Combination organic acid dips prolonged the lag phase for 2 to 6 wk on turkey product surfaces and can be useful as antimicrobial agents for Lm control on postlethality exposed sliced deli products.
Hemophagocytic Lymphohistiocytosis and Gastrointestinal Bleeding: What a Surgeon Should Know
Authors: Popeskou S. , Gavillet M. , Demartines N. , Christoforidis D.
Published: June 2015

This paper presents to the surgical community an unusual and often ignored cause of gastrointestinal bleeding. Hemophagocytic syndrome or hemophagocytic lymphohistiocytosis (HLH) is a rare medical entity characterized by phagocytosis of red blood cells, leucocytes, platelets, and their precursors in the bone marrow by activated macrophages. When intestinal bleeding is present, the management is very challenging with extremely high mortality rates. Early diagnosis and treatment seem to be the most important factors for a successful outcome. We present two cases and review another 18 from the literature.
Psychiatric Patients Experiences with Mechanical Restraints: An Interview Study
Authors: Lanthén Klas , Rask Mikael , Sunnqvist Charlotta
Published: June 2015

Objective. To examine psychiatric patients’ experience of mechanical restraints and to describe the care the patients received.Background. All around the world, threats and violence perpetrated by patients in psychiatric emergency inpatient units are quite common and are a prevalent factor concerning the application of mechanical restraints, although psychiatric patients’ experiences of mechanical restraints are still moderately unknown.Method. A qualitative design with an inductive approach were used, based on interviews with patients who once been in restraints.Results. This study resulted in an overbridging theme:Physical Presence, Instruction and Composed Behaviour Can Reduce Discontent and Trauma, including five categories. These findings implicated the following: information must be given in a calm and sensitive way, staff must be physically present during the whole procedure, and debriefing after the incident must be conducted.Conclusions. When mechanical restraints were unavoidable, the presence of committed staff during mechanical restraint was important, demonstrating the significance of training acute psychiatric nurses correctly so that their presence is meaningful. Nurses in acute psychiatric settings should be required to be genuinely committed, aware of their actions, and fully present in coercive situations where patients are vulnerable.
Noncirrhotic Extrahepatic Portosystemic Shunt Causing Adult-Onset Encephalopathy Treated with Endovascular Closure
Authors: Elnekave Eldad , Belenky Eugenia , Van der Veer Lindsley
Published: June 2015

A 54-year-old woman presented with a six-month history of episodic confusion and progressive ataxia. A comprehensive metabolic panel was notable for elevated values of alkaline phosphatase (161 U/L), total bilirubin (1.5 mg/dL), and serum ammonia of 300 umol/L (normal range 9–47). Hepatitis panel, relevant serological tests, tumor markers (CA-19-9, CEA), and urea cycle enzyme studies were unrevealing. Lactulose and rifaximin therapy failed to normalize serum ammonia levels. Imaging revealed a structural vascular abnormality communicating between an enlarged inferior mesenteric vein and the left renal vein, measuring 16 mm in greatest diameter. The diagnosis of congenital extrahepatic portosystemic shunt was made and endovascular shunt closure was performed using a 22 mm Amplatzer II vascular plug. Within a day, serum ammonia levels normalized. Lactulose and rifaximin were discontinued, and confusion and ataxia resolved.
Genetic or Psychogenic? A Case Study of “Folie à Quatre” Including Twins
Authors: Ohnuma Tohru , Arai Heii
Published: June 2015

Shared psychotic disorder, characterized by shared delusion among two or more subjects (termed “Folie à deux,” “trois,” etc.), is often associated with strong religious beliefs or social isolation, factors creating strong psychological sympathy. Recently, we treated a rare familial case of “Folie à quatre” in central Tokyo without such influences. The proband was a schizophrenia patient and younger brother within monozygotic twins. Positive symptoms were “transmitted” to remaining family members, his elder brother, mother, and father father, in a relatively short period of three months. Although the pathophysiology of these positive symptoms (delusions and hallucinations) remains unclear, the transmission pattern suggests the primacy of social and environmental factors (and/or their interaction), while genetics appeared less influential in this “Folie à famille.” Although undiagnosed psychoses in the whole family cannot be excluded, they did not share the other negative schizophrenia symptoms of the proband. A strong familial connection appeared to be the most important factor for the common delusion and hallucination.
The HOXB13 G84E Mutation Is Associated with an Increased Risk for Prostate Cancer and Other Malignancies
Authors: Beebe-Dimmer Jennifer L. , Hathcock Matthew , Yee Cecilia , Okoth Linda A. , Ewing Charles M. , Isaacs William B. , Cooney Kathleen A. , Thibodeau Stephen N.
Published: June 2015

Background: A rare nonconservative substitution (G84E) in the HOXB13 gene has been shown to be associated with risk of prostate cancer. DNA samples from male patients included in the Mayo Clinic Biobank (MCB) were genotyped to determine the frequency of the G84E mutation and its association with various cancers.

Methods: Subjects were genotyped using a custom TaqMan (Applied Biosystems) assay for G84E (rs138213197). In addition to donating a blood specimen, all MCB participants completed a baseline questionnaire to collect information on medical history and family history of cancer.

Results: Forty-nine of 9,012 male patients were carriers of G84E (0.5%). Thirty-one percent (n = 2,595) of participants had been diagnosed with cancer, including 51.1% of G84E carriers compared with just 30.6% of noncarriers (P = 0.004). G84E was most frequently observed among men with prostate cancer compared with men without cancer (P < 0.0001). However, the mutation was also more commonly observed in men with bladder cancer (P = 0.06) and leukemia (P = 0.01). G84E carriers were more likely to have a positive family history of prostate cancer in a first-degree relative compared to noncarriers (36.2% vs. 16.0%, P = 0.0003).

Conclusions: Our study confirms the association between the HOXB13 G84E variant and prostate cancer and suggests a novel association between G84E and leukemia and a suggestive association with bladder cancer. Future investigation is warranted to confirm these associations in order to improve our understanding of the role of germline HOXB13 mutations in human cancer.

Impact: The associations between HOXB13 and prostate, leukemia, and bladder suggest that this gene is important in carcinogenesis. Cancer Epidemiol Biomarkers Prev; 24(9); 1366–72. ©2015 AACR.
Mevalonate Pathway Antagonist Suppresses Formation of Serous Tubal Intraepithelial Carcinoma and Ovarian Carcinoma in Mouse Models
Authors: Kobayashi Yusuke , Kashima Hiroyasu , Wu Ren-Chin , Jung Jin-Gyoung , Kuan Jen-Chun , Gu Jinghua , Xuan Jianhua , Sokoll Lori , Visvanathan Kala , Shih Ie-Ming , Wang Tian-Li
Published: June 2015

Purpose: Statins are among the most frequently prescribed drugs because of their efficacy and low toxicity in treating hypercholesterolemia. Recently, statins have been reported to inhibit the proliferative activity of cancer cells, especially those with TP53 mutations. Because TP53 mutations occur in almost all ovarian high-grade serous carcinoma (HGSC), we determined whether statins suppressed tumor growth in animal models of ovarian cancer.

Experimental Design: Two ovarian cancer mouse models were used. The first one was a genetically engineered model, mogp-TAg, in which the promoter of oviduct glycoprotein-1 was used to drive the expression of SV40 T-antigen in gynecologic tissues. These mice spontaneously developed serous tubal intraepithelial carcinomas (STICs), which are known as ovarian cancer precursor lesions. The second model was a xenograft tumor model in which human ovarian cancer cells were inoculated into immunocompromised mice. Mice in both models were treated with lovastatin, and effects on tumor growth were monitored. The molecular mechanisms underlying the antitumor effects of lovastatin were also investigated.

Results: Lovastatin significantly reduced the development of STICs in mogp-TAg mice and inhibited ovarian tumor growth in the mouse xenograft model. Knockdown of prenylation enzymes in the mevalonate pathway recapitulated the lovastatin-induced antiproliferative phenotype. Transcriptome analysis indicated that lovastatin affected the expression of genes associated with DNA replication, Rho/PLC signaling, glycolysis, and cholesterol biosynthesis pathways, suggesting that statins have pleiotropic effects on tumor cells.

Conclusions: The above results suggest that repurposing statin drugs for ovarian cancer may provide a promising strategy to prevent and manage this devastating disease. Clin Cancer Res; 21(20); 4652–62. ©2015 AACR.
Carbohydrate Malabsorption and Putative Carbohydrate-Specific Small Intestinal Bacterial Overgrowth: Prevalence and Diagnostic Overlap Observed in an Austrian Outpatient Center
Authors: Enko Dietmar , Kriegshäuser Gernot , Kimbacher Christine , Stolba Robert , Mangge Harald , Halwachs-Baumann Gabriele
Published: June 2015

Background/Aims: While lactose malabsorption is a well-investigated condition, few epidemiologic data are available for fructose and sorbitol malabsorption. The aim of this study was to assess the prevalence rates for primary lactose malabsorption, fructose and sorbitol malabsorption, and carbohydrate-specific small intestinal bacterial overgrowth (cs-SIBO) in an Austrian outpatient center. Methods: In total, 306 adult patients, who were primarily referred with suspected carbohydrate malabsorption by general practitioners to our outpatient clinic, underwent genetic testing (C/T-13910 polymorphism) for primary lactose malabsorption, and a combined hydrogen (H2)/methane (CH4) breath test for fructose (25 g) and sorbitol (12.5 g) malabsorption. Cohen's kappa (κ) was calculated for agreement between positive breath test results and self-reported symptoms during the test. Results: Seventy-eight (25.49%) patients were C/C-13910 homozygotes, indicating primary lactose malabsorption. Thirty-four (11.11%) and 57 (18.63%) patients were classified as fructose and sorbitol malabsorbers. Cohen's κ measuring agreements between positive fructose and sorbitol breath test results and self-reported symptoms during the test were 0.33 and 0.49, respectively. Twenty-nine (9.50%) patients with an early H2/CH4 peak (i.e. within 60 minutes after fructose and/or sorbitol ingestion) were diagnosed with cs-SIBO. Conclusion: In Austria, carbohydrate malabsorption is a frequent condition in patients referred by general practitioners to carbohydrate malabsorption testing.
The Solitary Pulmonary Nodule
Authors: Harzheim Dominik , Eberhardt Ralf , Hoffmann Hans , Herth Felix J.F.
Published: June 2015

Due to the high etiological diversity and the potential for malignancy, pulmonary nodules represent a clinical challenge, becoming increasingly frequent as the number of CT examinations rises. The topic gains even more importance as clear evidence for the effectiveness of CT screening was provided by the National Lung Screening Trial (NLST). Yet, the results were tempered by the high false-positive rate and the requirement of performing further diagnostic procedures. The management of those detected solitary pulmonary nodules is currently based on the individuals' risk of developing lung cancer, the pulmonary nodule characteristics and the capability of diagnostic and therapeutic approaches.
Neurointerventional Stenting and Antiplatelet Function Testing: To Do or Not to Do?
Authors: Kass-Hout Tareq , Alderazi Yazan J. , Amuluru Krishna , Jin Peter , Ayala Carlos , Prestigiacomo Charles , Gandhi Chirag D.
Published: June 2015

Background and Purpose: Platelet function testing in neurointerventional (NI) procedures is still controversial. We compared the clinical outcomes between antiplatelet responders and nonresponders based on the results of the VerifyNow (VN) testing method. Methods: This is a retrospective single-center analysis of all consecutive patients who underwent NI stenting procedures from January 2007 through July 2013 and had documented preprocedural aspirin (ASA) and clopidogrel VN assays. Patients were divided into two groups based on their responsiveness to antiplatelet. Baseline characteristics, good functional outcome measured by the modified Rankin Scale (mRS) at 90 days, combined procedural complication rate defined as postprocedural stroke, in-stent thrombosis, and intraoperative rupture were compared between the two groups. Results: Our cohort included 37 patients: 26 were in the responder group (RG) and 11 were in the nonresponder group (NRG). Baseline characteristics were similar between the two groups. Even though the combined complication rate was similar between the two groups [NRG: 2/11 (18%) vs. RG: 2/26 (7%); p = 0.33], there was a trend for a higher rate of good functional outcome (90-day mRS: 0-2) in the RG (22/22, 100%) as compared to the NRG (8/10, 80%) (p = 0.0907). Conclusion: Overall, utilizing the VN antiplatelet function testing did not significantly change the clinical outcome after the NI procedures. Larger randomized trials are warranted to provide a better understanding of the utility of the antiplatelet testing in NI stenting procedures.
Atopy and Asthma in Migrants: The Function of Parasites
Authors: Rottem Menachem , Geller-Bernstein Carmi , Shoenfeld Yehuda
Published: June 2015

Migration studies have shown that environmental factors in more developed and industrialized countries facilitate atopy and asthma in a time-dependent manner and are affected by age at immigration. Levels of immunoglobulin E are higher in immigrants than in the local population and gradually decrease to the levels of the general population. Parasitic infestation may function in the prevention and pathogenesis of atopic conditions in immigrants from developing countries. Helminths are associated with a reduced prevalence of clinically important atopic disorders, likely because of induction of a regulatory cell population mechanism. Improved understanding of the immunologic background of helminths and their protective function in humans has led to a growing interest in the possibility of reversal of allergies using parasites and the development of new therapies, such as immunomodulation for allergy using ova from parasites orally or intranasally. Strategies for primary prevention in high-risk atopic individuals and secondary prevention guidelines should be developed for populations in developing countries and for immigrants from developing countries to atopy-prevalent developed countries. Improved understanding of the function of parasitic infection in modulation of the immune response may lead to new therapeutic options for allergic conditions.
Improvement in Gemcitabine-Induced Thrombotic Microangiopathy with Rituximab in a Patient with Ovarian Cancer: Mechanistic Considerations
Authors: Murugapandian Sangeetha , Bijin Babitha , Mansour Iyad , Daheshpour Sepehr , Pillai Biju G. , Thajudeen Bijin , Salahudeen Abdulla K.
Published: June 2015

Gemcitabine is a potent and widely used anticancer drug. We report a case of gemcitabine-induced thrombotic microangiopathy (GCI-TMA), a known but not widely recognized complication of gemcitabine use, and our experience of treating GCI-TMA with rituximab. A 74-year-old woman was referred to our clinic for an evaluation of worsening renal function. She has recently been treated for ovarian cancer (diagnosed in 2011) with surgery (tumor debulking and bilateral salpingo-oophorectomy) along with cisplatin chemotherapy in 2012, followed by carboplatin/doxorubicin in 2013 and recent therapy for resistant disease with gemcitabine. Laboratory tests showed anemia, normal platelets and elevated lactate dehydrogenase. A peripheral smear revealed numerous schistocytes, and a kidney biopsy showed acute as well as chronic TMA. The patient continued on gemcitabine therapy, and treatment with plasma exchange was started. Since there was no response to treatment even after 5 sessions of plasma exchange, one dose of rituximab was given, which was associated with a drop in the creatinine level to 2 mg/dl. The pathogenesis of renal injury could be the effect of direct injury to the endothelium mediated by cytokines. Usual treatment includes withdrawing the drug and initiation of treatment with plasmapheresis with or without steroids. In cases resistant to plasmapheresis, treatment with rituximab can be tried. The mechanism of action of rituximab might be due to the reduced production of B‐cell‐dependent cytokines that drive endothelial dysfunction by depleting B cells. Patients receiving gemcitabine chemotherapy should be monitored for the development of TMA, and early treatment with plasma exchange along with rituximab might benefit these patients who already have a bad prognosis.
August Davis and the Free-Free
Authors: Gustafson David M.
Published: June 2015

August Davis (1852–1936) led a group of Swedish Free Mission Friends in America known as the Free-Free, an early branch of what is today the Evangelical Free Church of America. Davis and his followers were known for such phenomena as falling down in the Spirit, having ecstatic visions, uttering unintelligible sounds, communicating the Holy Spirit through the laying on of hands, and teaching the baptism of the Holy Spirit as a second work of grace. Such activities occurred mostly in Chicago, Illinois, and throughout western Minnesota between 1885 and 1900. Davis and the Free-Free had direct organizational ties in the Scandinavian Mission Society U.S.A. to emerging Swedish-American Pentecostals in Minnesota and South Dakota such as John Thompson, Mary Johnson, and Jacob Bakken. This group known pejoratively as the Free-Free is another of several impulses that birthed a distinctly Pentecostal form of Christianity in America.
Taxonomic notes on the Cephalaria sect. Atrocephalae (Caprifoliaceae) from Iran
Authors: Ranjbar Massoud , RANJBAR ZAHRA
Published: June 2015

Cephalaria bojnordensis (Caprifoliaceae) is described and illustrated as a new species from Khorasan Province, north-east Iran. The characters that distinguish this new species from C. microcephala and C. isurica are provided along with a key to the Iranian species in Cephalaria sect. Atrocephalae. In addition, a lectotype is designated for C. microcephala.
Cytotaxonomy of the Simuliidae (Diptera): a systematic and bibliographic conspectus
Authors: ADLER PETER H. , CROSSKEY ROGER W.
Published: June 2015

An annotated compilation of all chromosomal works (cytoconspectus) on the Simuliidae is presented, covering 577 species including 541 formally named species—24.8% of the world’s extant nominal species—and 36 formally unnamed species. The first published record of polytene chromosomes in a simuliid appeared in 1919, followed by an imposing body of chromosomal research, most notably since 1956. The bibliography assembled here includes 653 works containing novel chromosomal information on the Simuliidae. Cytotaxonomy of the Simuliidae began in 1951 in the Canadian laboratory of Klaus Rothfels and subsequently expanded worldwide. Although chromosomal study has been uneven across species, it has provided a rich database of the genetics of natural populations and much of the foundation for the modern taxonomy and systematics of the family. After peaking in the late 1980s, cytotaxonomic productivity became more sporadic as the molecular movement gained popularity, despite the potential that an integrated chromosomal and molecular approach holds.
Systematic review of diplommatinid land snails (Caenogastropoda, Diplommatinidae) endemic to the Palau Islands. (2) Taxonomic revision of Hungerfordia species with low axial ribs
Authors: YAMAZAKI KAZUNORI , YAMAZAKI MIDORI , UESHIMA REI
Published: June 2015

Hungerfordia Beddome, 1889 is a terrestrial caenogastropod genus of the family Diplommatinidae endemic to the Palau (Belau) islands. Hungerfordia is radiated within the Palau islands and exhibits substantial morphological diversity. In this paper, the taxonomy of Hungerfordia species with low axial ribs is revised. Hungerfordia polymorpha (Crosse, 1866), H. inflatula (Crosse, 1866), H. crassilabris crassilabris (Beddome, 1889), H. lutea lutea (Beddome, 1889), H. ringens ringens (Crosse, 1866), H. pyramis pyramis (Crosse, 1866), and H. aurea (Beddome, 1889) are redescribed based on the syntypes and newly collected materials. The following new taxa are described: H. aspera sp. nov., H. basodonta sp. nov., H. microbasodonta sp. nov., H. rudicostata sp. nov., H. unisulcata sp. nov., H. longissima sp. nov., H. eurystoma sp. nov., H. crenata sp. nov., H. crassilabris tridentata subsp. nov., H. crassilabris attenuata subsp. nov., H. lutea hemilaevis subsp. nov., H. loxodonta sp. nov., H. omphaloptyx sp. nov., H. robiginosa sp. nov., H. angaurensis sp. nov., H. ringens rotundata subsp. nov., H. ringens ventrinodus subsp. nov., H. pyramis pteroma subsp. nov., H. spinoscapula sp. nov.