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An 11-year-old boy presented with 2 weeks of intermittent headache, right orbital pain, and constant diplopia. Brain MRI showed dural thickening and enhancement of the right lateral cavernous sinus, right orbital apex, and tentorium. Initial cerebral spinal fluid analysis showed only mild pleocytosis, and serum diagnostics were unrevealing. The working diagnosis was Tolosa-Hunt syndrome. His pain and sixth nerve palsy resolved with corticosteroids. Five months after initial presentation, he developed new numbness of the right cheek, complete right ophthalmoplegia, and weakness and numbness of his right hand and leg, all of which were responsive to steroids. Fifteen months later, he returned to the emergency department with 2 weeks of left-sided headaches and acute diplopia. On examination, he had a left cranial nerve 6 palsy. Dural biopsy showed diffuse mononuclear inflammatory cell reaction consisting mostly of lymphocytes with no signs of granuloma formation, nor any epithelioid or giant cells. His clinical course was consistent with an autoinflammatory condition of unknown etiology. Genetic testing with an immunodeficiency panel showed a risk allele in NOD2 (nucleotide-binding oligomerization domain 2) c.3019dup (p.Leu1007Prof*2) that is associated with an increased risk for Crohn disease. His clinical condition had similarities to central nervous system sarcoidosis. Because of the similarities between our patient's clinical, imaging, and genetic findings and neurosarcoidosis, he was switched to a more targeted therapy-infliximab. His condition has since been stable for nearly 2 years. In conclusion, genetic testing should be considered in patients with suspected occult autoimmunity.

PURPOSE To compare the use of topical dilation drops vs topical drops with the addition of intracameral epinephrine in resident-performed cataract surgery and the effects on pupil expansion device (PED) use, surgical costs, and surgical times. SETTING Iowa City Veterans Affairs Medical Center, Iowa City, Iowa, USA. DESIGN Retrospective chart review. METHODS Resident-performed primary cataract surgical cases using topical dilation drops only or drops with the addition of intracameral epinephrine were analyzed for PED use, surgical time, and costs in all patients and in patients with a history of tamsulosin use. RESULTS In the topical group, PEDs were used in 31.1% of cases compared with 13.5% of cases in the intracameral group (P < .0001). History of tamsulosin use was noted in about one third of cases in both groups. For patients with a history of tamsulosin use, PED use decreased from 52.7% in the topical cases to 17.9% in the intracameral group (P < .0001). Surgical times were on average 7.1 minutes slower with PED use than without PED use. There was a medication savings of $50.44 USD per case in the intracameral group compared with the topical group. Factoring in the $100 to $130 USD per PED used, total surgical costs were $19 267 USD less in the intracameral group over 6 months. CONCLUSIONS Intracameral epinephrine with lidocaine decreases the need for PED use during cataract surgery, lowers intraoperative costs, and improves efficiency compared with topical dilation drops alone.

The Ra EDM experiment uses a pair of high voltage electrodes to search for the atomic electric dipole moment of $^{225}$Ra. We use identical, plane-parallel electrodes with a primary high gradient surface of 200 mm$^2$ to generate reversible DC electric fields. Our statistical sensitivity is linearly proportional to the electric field strength in the electrode gap. We adapted surface decontamination and processing techniques from accelerator physics literature to chemical polish and clean a suite of newly fabricated large-grain niobium and grade-2 titanium electrodes. Three pairs of niobium electrodes and one pair of titanium electrodes were discharge-conditioned with a custom high voltage test station at electric field strengths as high as $+52.5$ kV/mm and $-51.5$ kV/mm over electrode gap sizes ranging from 0.4 mm to 2.5 mm. One pair of large-grain niobium electrodes was discharge-conditioned and validated to operate at $\pm 20$ kV/mm with steady-state leakage current $\leq 25$ pA ($1\sigma$) and a polarity-averaged $98 \pm 19$ discharges per hour. These electrodes were installed in the Ra EDM experimental apparatus, replacing a copper electrode pair, and were revalidated to $\pm 20$ kV/mm. The niobium electrodes perform at an electric field strength 3.1 times larger than the legacy copper electrodes and are ultimately limited by the maximum output of our 30 kV bipolar power supply., Comment: 16 pages, 11 figures

Microparticle biosensors embedded in 3D tissue-mimics were spatiotemporally monitored in a completely automated pipeline using deep learning. Localization and estimation of microparticle response from OCT imaging was achieved using 3D convolutional neural networks. The automated pipeline was demonstrated using glucose-responsive microparticles as a proof-of-concept. Keywords: Optical coherence tomography, convolutional neural networks, biosensors, microparticles

Nearest neighbor search, a classic way of identifying similar data, can be applied to various areas, including database, machine learning, natural language processing, software engineering, etc. Secure nearest neighbor search aims to find nearest neighbors to a given query point over encrypted data without accessing data in plaintext. It provides privacy protection to datasets when nearest neighbor queries need to be operated by an untrusted party (e.g., a public server). While different solutions have been proposed to support nearest neighbor queries on encrypted data, these existing solutions still encounter critical drawbacks either in efficiency or privacy. In light of the limitations in the current literature, we propose a novel approximate nearest neighbor search solution, referred to as Sparser, by leveraging a combination of space-filling curves, perturbation, and Order-Preserving Encryption. The advantages of Sparser are twofold, strengthening privacy and improving efficiency. Specifically, Sparser pre-processes plaintext data with space-filling curves and perturbation, such that data is sparse, which mitigates leakage abuse attacks and renders stronger privacy. In addition to privacy enhancement, Sparser can efficiently find approximate nearest neighbors over encrypted data with logarithmic time. Through extensive experiments over real-world datasets, we demonstrate that Sparser can achieve strong privacy protection under leakage abuse attacks and minimize search time.

PURPOSE To evaluate the ease of replacement and capsular stability of a new fluid-filled, modular, accommodating intraocular lens (IOL) system composed of a monofocal base lens with a fluid lens clipped inside of it. SETTING John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. DESIGN Experimental study. METHODS Five New Zealand rabbits underwent bilateral phacoemulsification with implantation of the test lens (Juvene, LensGen, Inc.) in both eyes (4 rabbits), or a control IOL in 1 eye (AcrySof, Alcon Laboratories, Inc.) and the test IOL in the other (1 rabbit). At 2 weeks, the 4 rabbits with bilateral Juvene IOLs had the clipped-in fluid lens exchanged for a new fluid lens in 1 eye, and the base and fluid lenses exchanged for a control lens in the contralateral eye. Slitlamp examinations were performed weekly for 4 weeks. The globes were enucleated and evaluated with ultrasound biomicroscopy, grossly from the posterior Miyake-Apple view, and histopathologically. RESULTS Explantation/exchange of the fluid lens was considered straightforward by the surgeon. Explantation of the base lens (4) was also safely performed, albeit more demanding, without any signs of damage to the capsular bag under clinical, ultrasound biomicroscopy, and pathological examination in the exchanged eyes. Less capsular bag opacification was observed with the Juvene lens system. CONCLUSIONS Explantation/exchange of the fluid lens component, or both fluid and base lenses, of this new lens system can be safely accomplished if necessary, because of its modular design and the relative lack of postoperative capsular bag opacification associated with it.

PURPOSE To evaluate long-term uveal and capsular biocompatibility of a new fluid-filled modular accommodating intraocular lens (IOL) consisting of base and fluid lenses. SETTING John A. Moran Eye Center, University of Utah, Salt Lake City, UT, USA. DESIGN Experimental study. METHODS Bilateral phacoemulsification was performed on 8 rabbits; 1 eye received the test IOL (Juvene) and the other a hydrophobic acrylic control IOL (SA60AT). Slitlamp examinations were performed at postoperative weeks 1 and 4, and at months 2, 3, and 6. The rabbits were killed humanely at 6 months. After gross examination from the Miyake-Apple view, IOLs were removed for implant cytology. All globes were then processed for histopathologic examination. RESULTS Uveal biocompatibility was similar between test and control IOLs up to 6 months postoperatively. Anterior capsule opacification appeared absent in the test group, and posterior capsule opacification (PCO) was significantly less in comparison with the control group throughout the study. At 6 months, central PCO was scored as 0.12 ± 0.23 with test IOLs and as 4.0 ± 0 with control IOLs (P < .0001, 2-tailed t test: paired 2-sample for means). Histopathologic examination confirmed the relative lack of capsular opacification in test eyes in comparison to controls and the absence of toxicity in any eye. CONCLUSIONS Six weeks in the rabbit model corresponds to approximately 2 years in the human eye for PCO. In this model, the Juvene IOL maintained an open and expanded capsular bag, preventing overall capsular bag opacification while retaining excellent uveal and capsular biocompatibility.

BACKGROUND Baseline staging CT scans are performed on nearly every patient after the diagnosis of a sarcoma to evaluate for the presence of metastatic disease. These scans often identify abnormalities that may or may not be related to the known malignancy. Despite the high frequency of incidental findings, there is little guidance for clinicians faced with assessing these radiographic abnormalities. The interpretation of incidental findings is important because it may influence decisions regarding surveillance frequency, prognostic estimation, and surgical and medical intervention. QUESTIONS/PURPOSES The purpose of this study was to determine (1) the frequency of abnormal findings and indeterminate nodules on staging CT scans; (2) the natural history of indeterminate nodules identified at the time of sarcoma diagnosis; and (3) the factors associated with indeterminate nodules representing true metastatic disease. METHODS Between September 2010 and February 2016 we treated 233 patients with bone and soft tissue sarcomas. Of those, 227 (97%) had a staging CT scan of the chest or chest/abdomen/pelvis performed within 2 months of diagnosis. To be eligible for this retrospective study, a patient had to have a minimum of 6 months of radiographic followup after that initial CT scan. A total of 36 (16%) were lost to followup or did not have radiographic surveillance at least 6 months later, and 48 (21%) were excluded for other prespecified reasons, leaving 149 patients for evaluation. We recorded all abnormal findings listed in the official radiology CT report of the lung, bone, liver, and lymph nodes. We assessed progression of indeterminate nodules by reviewing radiology reports, which listed both size and number of findings, and clinical notes outlining the current assessment of disease status and treatment plan. If indeterminate nodules grew in size or number consistent with metastatic disease or were confirmed histologically, they were considered to represent true metastasis. Bivariate methods were used to investigate an association between various clinical factors, which were obtained from chart review, and progression of indeterminate nodules to clear metastatic disease. RESULTS One hundred thirty-five of 149 patients (91%) had at least one abnormal finding on a staging CT scan. Forty-nine patients (33%) presented with indeterminate lung nodules, 15 (10%) with indeterminate liver lesions, four (3%) with indeterminate bone lesions, and 57 (38%) with enlarged lymph nodes. Fifteen of the 49 patients with indeterminate lung nodules (31%), one of 15 liver nodules, zero of four bone lesions, four of 13 lymph nodes 1 to 2 cm in size, and two of 44 subcentimeter lymph nodes (4.5%) were clearly metastatic on followup. A primary tumor size ≥ 14 cm in greatest dimension was more suggestive of indeterminate nodules representing true metastatic disease compared with smaller primary tumors in both lung (eight of 10 compared with seven of 36 [19%]; odds ratio, 16.6; 95% confidence interval, 2.9-95.9; p < 0.001) and lymph nodes (six of 18 compared with zero of 36 [0%], p < 0.001). CONCLUSIONS It is extremely common for abnormal findings and incidental nodules to be present at the time of a staging CT scan in patients with sarcoma. Although patients with indeterminate nodules should have continued surveillance, it appears from this study that the majority of these findings do not represent true metastatic disease. Given a minimum followup of 6 months, it is possible the actual proportion of indeterminate lesions representing true metastatic disease may increase over time. LEVEL OF EVIDENCE Level III, prognostic study.

This paper investigates the privacy leakage of smart speakers under an encrypted traffic analysis attack, referred to as voice command fingerprinting. In this attack, an adversary can eavesdrop both outgoing and incoming encrypted voice traffic of a smart speaker, and infers which voice command a user says over encrypted traffic. We first built an automatic voice traffic collection tool and collected two large-scale datasets on two smart speakers, Amazon Echo and Google Home. Then, we implemented proof-of-concept attacks by leveraging deep learning. Our experimental results over the two datasets indicate disturbing privacy concerns. Specifically, compared to 1% accuracy with random guess, our attacks can correctly infer voice commands over encrypted traffic with 92.89\% accuracy on Amazon Echo. Despite variances that human voices may cause on outgoing traffic, our proof-of-concept attacks remain effective even only leveraging incoming traffic (i.e., the traffic from the server). This is because the AI-based voice services running on the server side response commands in the same voice and with a deterministic or predictable manner in text, which leaves distinguishable pattern over encrypted traffic. We also built a proof-of-concept defense to obfuscate encrypted traffic. Our results show that the defense can effectively mitigate attack accuracy on Amazon Echo to 32.18%.

Millions of smart home speakers, such as Amazon Echo and Google Home, have been purchased by U.S. consumers. However, the security and privacy of smart home speakers have not been rigorously examined, which raise critical security and privacy concerns. In this paper, we investigate untold and severe privacy leakage of smart home speakers. Specifically, we examine a new passive attack, referred to as voice command fingerprinting attack, on smart home speakers. We demonstrate that a passive attacker, who can only eavesdrop encrypted traffic between a smart home speaker and a cloud server, can infer users' voice commands and compromise the privacy of millions of U.S. consumers. We formulate the attacks by harnessing machine learning algorithms. In addition to leveraging accuracy, we propose a new privacy metric, named semantic distance, to assess the privacy leakage with natural language processing. Our experiment results on a real-world dataset suggest that voice command fingerprinting attacks can correctly infer 33.8% of voice commands by eavesdropping encrypted traffic. Our results also show that existing padding methods can diminish an attacker's accuracy to 14.7%, but would cause high communication overhead (548%) and long time delay (330%).

In a phase 1 clinical study, coadministration of the adsorbent-based DAV132 product together with the fluoroquinolone antibiotic moxifloxacin, while not affecting the plasma concentrations of the antibiotic, reduced by >99% exposure of the intestinal microbiota to the moxifloxacin., Background Antibiotics are life-saving drugs but severely affect the gut microbiome with short-term consequences including diarrhea and selection of antibiotic-resistant bacteria. Long-term links to allergy and obesity are also suggested. We devised a product, DAV132, and previously showed its ability to deliver a powerful adsorbent, activated charcoal, in the late ileum of human volunteers. Methods We performed a randomized controlled trial in 28 human volunteers treated with a 5-day clinical regimen of the fluoroquinolone antibiotic moxifloxacin in 2 parallel groups, with or without DAV132 coadministration. Two control goups of 8 volunteers each receiving DAV132 alone, or a nonactive substitute, were added. Results The coadministration of DAV132 decreased free moxifloxacin fecal concentrations by 99%, while plasmatic levels were unaffected. Shotgun quantitative metagenomics showed that the richness and composition of the intestinal microbiota were largely preserved in subjects co-treated with DAV132 in addition to moxifloxacin. No adverse effect was observed. In addition, DAV132 efficiently adsorbed a wide range of clinically relevant antibiotics ex vivo. Conclusions DAV132 was highly effective to protect the gut microbiome of moxifloxacin-treated healthy volunteers and may constitute a clinical breakthrough by preventing adverse health consequences of a wide range of antibiotic treatments. Clinical Trials Registration NCT02176005.

Summary Background Acute kidney injury occurs in one in four children admitted to an intensive care unit (ICU) and its severity is independently associated with increased patient morbidity and mortality. Early prediction of acute kidney injury has the potential to improve outcomes. In smaller, single-centre trial populations, we have previously derived and validated the performance of a renal angina index, a context-driven risk stratification system, to predict severe acute kidney injury in children and adolescents. Here, we tested the predictive accuracy of this index for severe acute kidney injury in a large heterogeneous population. Methods We did a prospective, observational study (AWARE) that recruited patients in the ICUs of 32 hospitals in nine countries across Asia, Australia, Europe, and North America. All patients aged between 3 months and 25 years who were admitted to an ICU at least 48 h previously were eligible. Exclusion criteria were a history of stage 5 chronic kidney disease (ie, estimated glomerular filtration rate 2 or on maintenance dialysis) or kidney transplantation in the preceding 90 days. Patients' medical records were reviewed to collect data up to 3 months before (serum creatinine only), daily during the first 7 days, and on day 28 after ICU admission. For the assessment of the renal angina index, we included patients from the AWARE study who had full data from the day of ICU admission, day 3, and day 28, including serum creatinine concentrations and urine output measurements. The primary outcome was the presence of severe acute kidney injury (stage 2–3 acute kidney injury, according to Kidney Disease Improving Global Outcomes [KDIGO] guidelines) on the third day after ICU admission. We compared the performance of the renal angina index with changes in serum creatinine relative to baseline for prediction of the primary outcome. A score of eight points or more on the renal angina index defined fulfilment of renal angina; serum creatinine concentration relative to baseline was calculated using maximum serum creatinine concentration in the first 12 h of ICU admission). This trial is registered with ClinicalTrials.gov, number NCT01987921. Findings Between Jan 1 and Dec 31, 2014, we obtained data for 1590 patients. 286 patients (18%) had fulfilment of renal angina. At day 3, severe acute kidney injury occurred in 121 (42%) patients positive for renal angina and 247 (19%) patients negative for renal angina (relative risk [RR] 2·23, 95% CI 1·87–2.66, p vs 18 [2%], p vs 53 [4%], p=0·01). Fulfilment of renal angina showed better prediction for severe acute kidney injury than serum creatinine greater than baseline (RR 1.61, 95% CI 1·33–1·93; p vs serum creatinine greater than baseline 0·68, 0·49–4·94). Interpretation Earlier and better prediction of severe acute kidney injury has the potential to improve patient outcomes associated with acute kidney injury. Compared with isolated, context-free changes in serum creatinine, renal angina risk assessment improved accuracy for prediction of severe acute kidney injury in critically ill children and young people. Funding US National Institutes of Health.

Summary We designed a PyQt graphical user interface—Sequanix—aimed at democratizing the use of Snakemake pipelines in the NGS space and beyond. By default, Sequanix includes Sequana NGS pipelines (Snakemake format) (http://sequana.readthedocs.io), and is also capable of loading any external Snakemake pipeline. New users can easily, visually, edit configuration files of expert-validated pipelines and can interactively execute these production-ready workflows. Sequanix will be useful to both Snakemake developers in exposing their pipelines and to a wide audience of users. Availability and implementation Source on http://github.com/sequana/sequana, bio-containers on http://bioconda.github.io and Singularity hub (http://singularity-hub.org). Supplementary information Supplementary data are available at Bioinformatics online.

3615 Background: Location and somatic gene signature of CRCs may impact prognosis and therapy response. The aim was to characterize colon Microbiota in CRC patients regarding location, gene markers and outcome. Methods: Patients (N = 173) signed consent for whole metagenome (shot gun sequencing on Illumina HiSeq2500) analysis of stool DNA: 72 CRC (53 sporadic-S, 19 Lynch-L), 87 asymptomatic subjects (normal colonoscopy), 14 first degree healthy relatives from Lynch families. "MOCAT" pipeline was used, library sorted (Phred quality score ¡20 Alientrimmer v0.4.0) after exclusion of < 35 nt, human genes or phage sequences. Quality sequences were aligned (REFMG.V13) and most abundant genes constructed (MBMA program v0.1). The Shaman program (shaman.c3bi.pasteur.fr) was used. The number of bacteria was estimated (REFMG program). The linear model (GLM) was implemented in the DESeq2 R kit. Dfferences between Control (N = 87) and CRCs (N = 69), between L (N = 19) and S CRCs(N = 50), and between LCRC (N = 19) and Healthy Lynch relatives were obtained after interaction of age, BMI and gender was considered (GLM model). The P < 0.1 value was retained after correction (Benjamini and Hochberg). The specific taxonomic composition of the control and CRC groups was subjected to random analysis ( Caret's R package) with two optimization parameters (precision and kappa) in the model. Results: There was no difference for gender, age (p = 0.08) and BMI (p = 0.187) in the L and S CRCs. Significant differences were observed between Normal and CRCs, C-CRC and L-CRC, L-CRC and first degree relatives based on the common component (similarity of sequences): 13 species differentiated Normal and CCRs, two were more prevalent in L-CRCs. The panels of bacteria linked with location, MSI, Ras mutations, methylation phenotypes and survival were identified. No significant link was observed with TNM Staging: I (N = 17, 2L and 15S), II (N = 12, 5L and 7S), III (N = 20, 10L, 10S), IV (N = 22.1L, 21S). DFS might be dysbiosis dependent. Conclusions: CRC dysbiosis is location-dependent. Several bacteria are associated with Ras mutation, MSI, and methylation status. They may directly or through therapies impact the prognosis. Microbiota signature should be taken in consideration in trials.

We study mobile user behavior from cell-level location trace (CLLT). Since CLLT contains no GPS coordinates of mobile users, we infer approximate user locations from the cell locations they visit. We build upon the vast literature on user behavior analysis and demonstrate the ability to extract user behavior in the absence of the more precise GPS information. We focus on the “leisure time” behavior, i.e. activities outside home and office. In particular, we compare pairs of users and study their similarity or the lack of it. Such similarity comparison can be done directly using the users' actual cell-level locations and the times of their visits. We observe that a user's behavior on different days tends to be more similar to oneself than to others. We then compare users in terms of their activities irrespective of physical locations. We develop the notion of semantic cell type which classifies the cells according to the consistency of points of interest within the cells. In this way, we can compare two users based on the type of cells they visit and extract similarity from there. As a result, we gain understanding of the general profiles of the cells and the users. We are able to differentiate user behavior and cluster them in a meaningful way.

The ubiquitous deployment of IEEE 802.11 based Wireless Mesh Networks (WMNs) has facilitated non-real-time applications effectively to date. However the advancement in IEEE 802.15.4 Wireless Sensor Network (WSN) technology has dramatically increased the volume and range of applications available under the umbrella of the Internet of Things (IoTs). Such applications cross the divide of simple environmental data collectors to highly specific multimedia real-time applications demanding high Quality of Service (QoS) guarantees. However delivering QoS guarantees is difficult to achieve when deployed in a hostile environment such as that found in the Precision Agriculture (PA) industry. Difficulties in wireless propagation attenuation delivers an uncertainty to the network design phase. Therefore the motivation of this research is a requirement for real-time characterisation and derivation of suitable propagation models to support network design and deployment planning. In this work, empirical results were collected from a heterogeneous wireless deployment (the real-world ECOMESH test-bed) in a native woodland environment. We derive two empirical models which can be utilised in predicting attenuation network performance in two different scenarios. These models deliver the first phase of a Dynamic Network Management System for maintaining QoS guarantees in heterogeneous wireless networks.

Multi-media applications for use in Precision Agriculture (PA) and Smart Farming (SM) require Network Management Systems to deliver Quality of Service (QoS) end-to-end guarantees. This paper presents the second phase of the research in providing a network management system capable of delivering end-to-end QoS guarantees for Internet of Things (IOT) networks. The first phase of this work used a wireless test bed to develop a propagation model to incorporate the attenuation due to foliage in dense vegetation typically found in PA environments. The output of this propagation model will influence the decision making process in the network management system. Wireless Multimedia Sensor Networks (WMSN) operate under the umbrella of the Wireless Sensor Network (WSN) IEEE 802.15.4 Medium Access Control (MAC) and Physical (PHY) protocol to deliver multimedia applications such as voice, video and live streaming. To operate successfully these multi-media applications have high QoS requirements. To enable these QoS requirements to be fulfilled performance metrics such as throughput, end-to-end delay and limited packet loss must be guaranteed. This next phase of the work in developing the intelligent network management system presented in this paper uses an OPNET™ simulation package to implement a modified K-Means algorithm to detect the presence of multi-media traffic. Consequently a signal informs the network management system to adopt pre-configured settings via the Personal Area Network Co-ordinator (PANC). The resulting changes implement service differentiation by manipulating the MAC layer (size of the individual GTS timeslots and duty cycle) to deliver better throughput and end-to-end delay performance. OPNET™ simulation results show that the new algorithm facilitates better performance and meets QoS requirements suitable to multimedia applications. This paper focuses on the derivation and evaluation of the performance of the K-Means algorithm. The sensory nodes are power, memory and computationally restricted. These restrictions coupled with the heterogeneous structure of the wireless network make intelligent network management systems very important if the QoS requirements are to be fulfilled. Upon detection of multimedia traffic with high QoS demands usually triggered in the aftermath of an event of particular interest e.g. security threat etc., a management system must dynamically effect change of the network configuration settings to maintain such guarantees. As real-time applications require an urgent response, the dynamic change must occur during run time automatically. This research work is novel in that it combines the output from the development of the physical layer propagation model to inform a network management system to trigger service differentiation for multimedia traffic in a PA environment.

WSN technology has now become ubiquitous due to its flexibility, efficiency and affordability. For example the nodes in a WSN can be easily deployed in any targeted area and last for many years. The nodes can supply reliable data from within the environment with minimal disturbance to the target area.However challenges remain in providing real-time communication in some communication hostile conditions. It may not always be possible to leave the sensors in situ but instead data collection is through the use of mobile a WSN. For example as a vehicle fitted with sensing devices passes through an area of interest data is collected and relayed at certain gateway nodes back to a backhaul network for processing.In this paper our aim is to analyse the interference caused by a mobile jammer node to the stationary transmitter and receiver nodes in a network by using the OPNET Modeler software. This is early stage work aimed at developing a mobile WSN node in our future research.

Wireless Sensor Networks and the smart applications designed to operate upon them have enjoyed a rapid increase in popularity over the last decade. The main challenge currently is the provision of real-time service delivery for wireless sensor networks to cater for new applications with guaranteed Quality of Service (QoS) requirements. However each application has a different service requirement. In order to deliver real-time services the dimensioning of such networks is important to service providers in order to meet these service requirements. If packets cannot be stored due to insufficient memory they are lost. Lost packets result in the resending of the packets and hence an increase in delay in delivery of the application traffic. It is this memory provisioning of these wireless sensor networks that is the focus of the work presented in this paper. More specifically the relationship between the application design, implementation and memory resources required to run the service are explored using a stack analysis tool. This stack analysis tool enables the stack footprint to be measured. Results of memory usage for two different WSN applications are presented. Recommendations based on this study for efficient memory provisioning and ultimately real-time service delivery are given.

Adenoviral vectors (Ads) are promising gene delivery vehicles due to their high transduction efficiency; however, their clinical usefulness has been hampered by their immunogenicity and the presence of anti-Ad immunity in humans. We reported the efficacy of a gene therapy approach for glioma consisting of intratumoral injection of Ads encoding conditionally cytotoxic herpes simplex type 1 thymidine kinase (Ad-TK) and the immunostimulatory cytokine fms-like tyrosine kinase ligand 3 (Ad-Flt3L).Herein, we report the biodistribution, efficacy, and neurological and systemic effects of a bicistronic high-capacity Ad, i.e., HC-Ad-TK/TetOn-Flt3L. HC-Ads elicit sustained transgene expression, even in the presence of anti-Ad immunity, and can encode large therapeutic cassettes, including regulatory elements to enable turning gene expression "on" or "off" according to clinical need. The inclusion of two therapeutic transgenes within a single vector enables a reduction of the total vector load without adversely impacting efficacy. Because clinically the vectors will be delivered into the surgical cavity, normal regions of the brain parenchyma are likely to be transduced. Thus, we assessed any potential toxicities elicited by escalating doses of HC-Ad-TK/TetOn-Flt3L (1×108, 1×109, or 1×1010 viral particles [vp]) delivered into the rat brain parenchyma. We assessed neuropathology, biodistribution, transgene expression, systemic toxicity, and behavioral impact at acute and chronic time points. The results indicate that doses up to 1×109 vp of HC-Ad-TK/TetOn-Flt3L can be safely delivered into the normal rat brain and underpin further developments for its implementation in a phase I clinical trial for glioma. Fil: Puntel, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. University of Michigan. School of Medicine; España. Cedars Sinai Medical Center; Estados Unidos Fil: Ghulam Muhammad, A. K. M.. Cedars Sinai Medical Center; Estados Unidos Fil: Farrokhi, Catherine. Cedars Sinai Medical Center; Estados Unidos Fil: VanderVeen, Nathan. University of Michigan. School of Medicine; España Fil: Paran, Christopher. University of Michigan. School of Medicine; España Fil: Appelhans, Ashley. University of Michigan. School of Medicine; España Fil: Kroeger, Kurt M.. Cedars Sinai Medical Center; Estados Unidos Fil: Salem, Alireza. Cedars Sinai Medical Center; Estados Unidos Fil: Lacayo, Liliana. Cedars Sinai Medical Center; Estados Unidos Fil: Pechnick, Robert N.. University of California at Los Angeles; Estados Unidos Fil: Kelson, Kyle R.. Cedars Sinai Medical Center; Estados Unidos Fil: Kaur, Sukhpreet. Cedars Sinai Medical Center; Estados Unidos Fil: Kennedy, Sean. Cedars Sinai Medical Center; Estados Unidos Fil: Palmer, Donna. Baylor College of Medicine; Estados Unidos Fil: Ng, Philip. Baylor College of Medicine; Estados Unidos Fil: Liu, Chunyan. Cedars Sinai Medical Center; Estados Unidos Fil: Krasinkiewicz, Johnny. University of Michigan. School of Medicine; España Fil: Lowenstein, Pedro R.. Cedars Sinai Medical Center; Estados Unidos. University of Michigan. School of Medicine; España. University of California at Los Angeles; Estados Unidos Fil: Castro, Maria G.. Cedars Sinai Medical Center; Estados Unidos. University of Michigan. School of Medicine; España. University of California at Los Angeles; Estados Unidos

Through detailed analysis of scores of publicly available data sets corresponding to a wide range of large-scale networks, from communication and road networks to various forms of social networks, we explore a little-studied geometric characteristic of real-life networks, namely their hyperbolicity. We provide strong evidence that large-scale communication and social networks exhibit this fundamental property, and through extensive computations we quantify the degree of hyperbolicity of each network in comparison to its diameter. By contrast, and as evidence of the validity of the methodology, applying the same technique to graphs of road networks shows that they are not hyperbolic, which is as expected. Finally, we present practical computational means for detection of hyperbolicity and show how the test itself may be scaled to much larger graphs than those we examined via renormalization group methodology.

The Internet of Things (IoT) network is typified by deployments such as a Wireless Sensor Network (WSN). These WSN's are commonly deployed within a target area for a specific task such as farm monitoring and asset movement control. A group of sensors are typically led by a Personal Area Network Coordinator (PANC). In some situations like in large scale greenhouse monitoring, mobile PANC are required to eliminate energy-hole issues and hence improve the performance of the WSN. The energy-hole issue is a problem caused by the depleted cluster head nodes. In this paper we analyse the performance of a WSN with a mobile PANC. Using inputs from previous empirical studies we designed a scenario of a mobile PAN coordinator using a simulation package. The performance was evaluated. The mobile PANC speed and contact time is monitored and the average network throughput and delay are measured. Based on an analysis of these results a comprehensive set of guidelines are provided for operators of IoT networks. These guidelines optimise the network performance and ultimately lead to cost savings for network providers.

To compare the distribution of tenofovir in sheep vaginal lumen, tissue, and plasma following topical delivery of the antiretroviral drug from intravaginal rings, either as tenofovir or the disoproxil fumarate prodrug.Comparative pharmacokinetic study in sheep.Intravaginal rings formulated to achieve equivalent release rates of tenofovir and its disoproxil fumarate prodrug were evaluated for 28 days in sheep, with four animals in each group. Drug concentrations were measured by high-performance liquid chromatography-mass spectrometry.Tenofovir levels in cervicovaginal lavage were indistinguishable (P 0.30) in both groups, but tissue levels in animals receiving the prodrug were 86-fold higher than those receiving tenofovir, and approximately 50 times higher than the level shown to be protective of HIV infection in the CAPRISA 004 trial.This is the first study to compare the pharmacokinetics of tenofovir and its disoproxil fumarate prodrug administered topically to the vaginal tract. These in-vivo data show that the prodrug leads to significantly higher drug tissue levels than tenofovir, a finding that may have important implications for the development of preexposure prophylaxis strategies based on topical delivery of antivirals to the female genital tract.

Background: Left ventricular hypertrophy (LVH) is a pathological remodeling of myocardial tissue occurring in response to an increase in cardiac workload. The most significant cause of LVH in the pediatric population is aortic valve disease, which includes aortic valve stenosis and insufficiency. Though LVH can arise naturally in response to strenuous exercise, it has clinical utility as a marker of hypertension and heart disease. LVH can be detected using certain voltage criteria via electrocardiogram (ECG), though this approach typically exhibits poor sensitivity. The current gold standard for LVH identification is echocardiogram – however, waiting times and operator skill are significant variables in echocardiographic diagnosis of LVH. This study evaluates the sensitivity and specificity of various voltage criteria for LVH in this population, and whether amalgamating criteria can boost their accuracy. Methods: A retrospective chart review was conducted to look at the echocardiograms and electrocardiograms (ECGs) of 62 pediatric patients with aortic valve disease seen at McMaster University Medical Centre. Patient ECGs were analyzed for LVH using a number of voltage criteria: those established by the Journal of American College of Cardiology’s (JACC) standards for pediatric LVH, criteria utilized for adult LVH, and Cornell adult voltage criteria. To determine the suitability of these indices in identifying LVH via ECG, we analyzed sensitivity, specificity and negative predictive value (NPV) of each set of criteria using echocardiograms carried out within 2 months as a gold standard. Results: Our results identify Cornell Female voltage criteria as bearing the highest sensitivity (81.94%) in identifying LVH in this population, while JACC pediatric criteria demonstrated the highest specificity (77.29%). Using Cornell Female voltage criteria as a sensitive screening tool, we then applied JACC pediatric criteria (chosen for its high specificity). The combined criteria (JACCCF) demonstrated higher sensitivity and specificity (88.64% and 83.33%, respectively) than either criteria used in isolation. Conclusion: Cornell Female voltage criteria demonstrated the highest sensitivity in this population, though it is typically not utilized in a pediatric setting. Utilizing Cornell Female criteria as a screening tool in tandem with JACC criteria for its specificity yielded a set of highly specific and sensitive criteria. This approach bears promise in pediatric patients with aortic valve disease, and should be explored in other populations with LVH.

International audience; Background. During antibiotic treatments, antibiotics reach the colon and alter the microbiome, resulting in emergence and dissemination of resistant bacteria, antibiotic-associated diarrhea (AAD) and occurrence of Clostridium difficile (Cd) infections (CDI). We developed an oral adsorbent-based product, DAV132, to be co-administered with antibiotics in order to prevent these effects. We report here the results of protection of the microbiome in human volunteers treated with oral moxifloxacin (MOX), and protection against CDI in vitro in a human gut model (HGM) and in vivo in experimental hamsters.Methods. Four groups (MOX [400 mg OD for 5 days], MOX + DAV132 [7.5 g TID for 7 days], DAV132, or control) of healthy volunteers (n = 44) were included in a randomized clinical trial. Feces were collected at screening, daily from D1 to D9 and at D12, D16, D23, D30, D37 and plasma PK assayed at D1and5. Metagenomic analyses were done by shotgun sequencing at screening, D3, D6, D9, D16 and D37. The effect of DAV132 on MOX was also assessed in a HGM inoculated with Cd spores (ribotype 027, MOX MIC 32 mg/L); bacterial counts, toxin production and MOX concentrations were measured over time. MOX dosed hamsters were inoculated with 104 spores of a non-epidemic Cd (TcdA + , TcdB + , cdtB−) and treated ±DAV132. Mortality and Cd counts were assessed over time.Results. In humans, DAV132 was well tolerated and decreased free fecal MOX by > 99% compared to MOX alone: ratio of mean LogAUCD1-D16 = 0.0093 (95% CI 0.0061-0.0144), p = 0.03 × 10−16; MOX plasma PK was not changed significantly. Alterations of the fecal microbiome observed with MOX were prevented. In the HGM, DAV protected the microbiota and prevented Cd overgrowth and toxin production. Hamsters were fully protected by DAV against MOX-induced CDI (dose dependent), with decreased free fecal MOX and Cd counts.Conclusion. DAV132 protects humans against fecal microbiome disruption after oral MOX treatment, without altering its plasma PK. In vitro results in HGM and in vivo results in hamsters suggest that DAV132 should be protective against antibiotic-induced CDI. These results warrant further clinical development of DAV132 to protect the intestinal microbiota, and so prevent AAD and CDI, in patients receiving oral or parenteral antibiotics.

Wireless Sensor Networks (WSNs) are formed with multiple sensor nodes that use the IEEE 802.15.4 protocol. The WSN can operate in 16 different channels in the unlicensed Industrial, Scientific and Manufacturing (ISM) 2.4 GHz spectrum. The WLAN or IEEE 802.11g/n protocol also operates in the same spectrum. Additional problems arise when the WSN is mobile. Mobile WSN's are more efficient in scenarios where mobility is needed to collect data from remote target areas. Moving nodes may encounter overlapping frequencies from WLAN coexistence in its journey. Therefore, WSN channels have to be allocated intelligently to avoid channels overlapping with the WLAN. However with mobile WSN the WLAN networks encountered may have random spectrum allocation depending on the WLAN technology in place. A good resource allocation approach is needed for the sensor nodes to dynamically change their working channel to avoid the overlapping channels which cause interference to the network (either WSN or WLAN) which impacts the service delivery. This paper focuses on the interference when the mobile WSN and WLAN both exist in the same building. The analysis presented is based on the percentage of packets dropped and percentage of packet re-transmitted for each sensor node in the experiments. The outcome of this research will be valuable to research and development of WSN applications in terms of reliable service delivery.

OBJECTIVE: To describe severity of emotional and physical symptoms in a large diverse sample; to examine demographic, health status, and behavioral correlates of symptom severity; and to describe use of medications and alternative remedies for premenstrual symptoms. METHODS: A total of 1194 women, ages 21–45, selected from members of a large northern California health maintenance organization, completed daily ratings of symptom severity for two menstrual cycles. An empirically derived algorithm defined symptom severity groups as minimal (n = 186), moderate (n = 801), severe (n = 151), or premenstrual dysphoric disorder (n = 56). Symptom severity as a continuous variable was defined by the two-cycle mean symptom ratings in the luteal phase. Demographic, health status, and behavioral factors and use of treatments for premenstrual symptoms were assessed by self-report. RESULTS: Luteal phase symptom-specific ratings were generally significantly greater in the premenstrual dysphoric disorder group than in the other groups (P < .001). Symptom severity score increased with each comorbidity and decreased with each year of age. Symptom severity was also inversely associated with oral contraceptive use (emotional symptoms) and better perceived health (physical symptoms). Hispanics reported greater severity of symptoms, and Asians less, relative to whites. Use of herbal and nutritional supplements for premenstrual symptoms steadily increased from 10.8% in the minimal group to 30.4% in the premenstrual dysphoric disorder group (P < .01). CONCLUSION: The degree of premenstrual symptom severity varies in the population, is relatively constant within each woman over two consecutive cycles, particularly for emotional symptoms, and is influenced by age, race/ethnicity, and health status.

Summary Objectives In this article we present the findings from a scoping review that sought to identify what is known about the experiences of paramedic students transitioning into the workforce. Background Within the emergency healthcare sector, paramedics are primarily tasked with the assessment, treatment and safe transport of patients to hospital. New paramedics entering the workforce are exposed to the full extent of human emotion, injury and suffering as part of their everyday work. There is evidence from other healthcare disciplines that the transition to practice period can be difficult for new graduates. Methods We utilised Arksey and O'Malley's five-stage scoping review framework to identify what is known about the transition of paramedicine graduates to the workplace. The framework involves identifying relevant studies; study selection; charting the data; and collating, summarizing and reporting results. Results We identified eleven articles that explored transition of newly qualified paramedics. Thematic content was identified and discussed into four separate categories. Each theme revealing the emotional, physical and social impacts new paramedics face as they strive to find acceptance in a new workplace and culture. Conclusion Given the significant role that paramedics have in modern healthcare, the transition from student to practitioner is a period of significant stress to the new paramedic. Limited research in this field though inhibits a thorough understanding of these issues.

International audience; The gut microbiota (GM) consists of resident commensals and transient microbes conveyed by the diet but little is known about the role of the latter on GM homeostasis. Here we show, by a conjunction of quantitative metagenomics, in silico genome reconstruction and metabolic modeling, that consumption of a fermented milk product containing dairy starters and Bifidobacterium animalis potentiates colonic short chain fatty acids production and decreases abundance of a pathobiont Bilophila wadsworthia compared to a milk product in subjects with irritable bowel syndrome (IBS, n=28). The GM changes parallel improvement of IBS state, suggesting a role of the fermented milk bacteria in gut homeostasis. Our data challenge the view that microbes ingested with food have little impact on the human GM functioning and rather provide support for beneficial health effects.

Background Microbial communities of traditional cheeses are complex and insufficiently characterized. The origin, safety and functional role in cheese making of these microbial communities are still not well understood. Metagenomic analysis of these communities by high throughput shotgun sequencing is a promising approach to characterize their genomic and functional profiles. Such analyses, however, critically depend on the availability of appropriate reference genome databases against which the sequencing reads can be aligned. Results We built a reference genome catalog suitable for short read metagenomic analysis using a low-cost sequencing strategy. We selected 142 bacteria isolated from dairy products belonging to 137 different species and 67 genera, and succeeded to reconstruct the draft genome of 117 of them at a standard or high quality level, including isolates from the genera Kluyvera, Luteococcus and Marinilactibacillus, still missing from public database. To demonstrate the potential of this catalog, we analysed the microbial composition of the surface of two smear cheeses and one blue-veined cheese, and showed that a significant part of the microbiota of these traditional cheeses was composed of microorganisms newly sequenced in our study. Conclusions Our study provides data, which combined with publicly available genome references, represents the most expansive catalog to date of cheese-associated bacteria. Using this extended dairy catalog, we revealed the presence in traditional cheese of dominant microorganisms not deliberately inoculated, mainly Gram-negative genera such as Pseudoalteromonas haloplanktis or Psychrobacter immobilis, that may contribute to the characteristics of cheese produced through traditional methods. Electronic supplementary material The online version of this article (doi:10.1186/1471-2164-15-1101) contains supplementary material, which is available to authorized users.

With several studies estimating the health care costs attributable to obesity-related medical conditions, the economic consequences of being overweight are beginning to come into focus. The present study complements this growing body of literature by directly estimating health care costs across a broad range of body mass index values. Data were obtained from the 1987 National Medical Expenditure Survey (NMES) public use data tapes and retrospective analyses conducted on NMES Household Survey data only. The analyses included a total of 16,217 individuals between the ages of 18 and 65. Four classes of health care utilization and expenditures were derived using the NMES data: (1) use of any health care service and total health care expenditures, (2) use of inpatient services and inpatient expenditures, (3) use of outpatient services and outpatient expenditures, and (4) use of prescription medication and medication expenditures. Estimates based on our findings suggested strong relationships between body mass and the likelihood of using health care services and between body mass and average annual health care expenditures for both men and women. Increased body mass was associated with increased expenditures. However, this association was greater among males than among females and did not hold for individuals in the lowest body mass category. Ideal body mass was associated with 6.3% to 36.1% lower annual health care expenditures among females and 3.6% to 18.2% lower health care expenditures among males. The results of this set of analyses suggest that health care expenditures increase as weight deviates from the ideal-that is, health care expenditures among both underweight and overweight individuals in the United States were increased in relation to ideal weight. Separate analyses including weight-related diseases such as diabetes and hypertension indicated that body mass increased health care expenditures largely by increasing the risk for these costly chronic medical conditions.

Multipurpose technologies that simultaneously protect from sexually transmitted infections and unintended pregnancy are urgently needed. Pod-intravaginal rings (IVRs) formulated with the antiretroviral agents (ARVs) tenofovir, nevirapine, and saquinavir and the contraceptives etonogestrel and estradiol were evaluated in sheep. Steady-state concentrations were maintained for 28 days with controlled, sustained delivery. This proof-of-principle study demonstrates that pod IVRs can deliver three ARVs from different mechanistic classes and a progestin-estrogen combination over the wide range needed for putative preventative efficacy.

User interactions over social networks has been an emergent theme over the last several years. In contrast to previous work we focus on characterizing user communications patterns around an initial post, or conversation root. Specifically, we focus on how other users respond to these roots and how the complete conversation initiated by this root evolves over time. For this purpose we focus our investigation on Twitter, the biggest micro-blogging social network. To the best of our knowledge this is the first such method that is able to reconstruct complete conversations around initial tweets. We propose a robust approach for reconstructing complete conversations and compare the resulting graph structures against those obtained from previous crawling strategies based on keyword searches. Our crawl provides a large scale dataset, ideal for computer scientists to run large scale experimental evaluations, however our dataset is made of a collection of small scale, highly controlled and complete conversation graphs ideal for a sociological investigation. We believe our work will provide the proper dataset to establish concrete collaborations with interdisciplinary expertise.

Semantic Web Services (SWS) are Web Service (WS) descriptions augmented with semantic information. SWS enable intelligent reasoning and automation in areas such as service discovery, composition, mediation, ranking and invocation. This paper applies SWS to a previous protocol adapter which, operating within clearly defined constraints, maps SOAP Web Services to RESTful HTTP format. However, in the previous adapter, the configuration element is manual and the latency implications are locally based. This paper applies SWS technologies to automate the configuration element and the latency tests are conducted in a more realistic Internet based setting.

Routine visual slide screening for identification of tuberculosis (TB) bacilli in stained sputum slides under microscope system is a tedious labor-intensive task and can miss up to 50% of TB. Based on the Shannon cofactor expansion on Boolean function for classification, a stepwise classification (SWC) algorithm is developed to remove different types of false positives, one type at a time, and to increase the detection of TB bacilli at different concentrations. Both bacilli and non-bacilli objects are first analyzed and classified into several different categories including scanty positive, high concentration positive, and several non-bacilli categories: small bright objects, beaded, dim elongated objects, etc. The morphological and contrast features are extracted based on aprior clinical knowledge. The SWC is composed of several individual classifiers. Individual classifier to increase the bacilli counts utilizes an adaptive algorithm based on a microbiologist's statistical heuristic decision process. Individual classifier to reduce false positive is developed through minimization from a binary decision tree to classify different types of true and false positive based on feature vectors. Finally, the detection algorithm is was tested on 102 independent confirmed negative and 74 positive cases. A multi-class task analysis shows high accordance rate for negative, scanty, and high-concentration as 88.24%, 56.00%, and 97.96%, respectively. A binary-class task analysis using a receiver operating characteristics method with the area under the curve (Az) is also utilized to analyze the performance of this detection algorithm, showing the superior detection performance on the high-concentration cases (Az=0.913) and cases mixed with high-concentration and scanty cases (Az=0.878).

This paper uses data from the Australian Workplace Industrial Relations Survey conducted in 1989–90 to examine the net impact of trade unions on the extent of formal types of employer‐provided training. A net positive effect is found, but only where unions are active in the workplace and not merely de jure representatives of the work‐force. The results also indicate, with respect to in‐house training, that unions shift the emphasis towards work‐forces with long tenure, a finding that is consistent with ‘union voice’ arguments. © 1994 Blackwell Publishing Ltd / London School of Economics

Vaginal microbicides may play an important role in protecting women from HIV infection. A strong synergy between HSV and HIV has been observed, and epidemiological studies demonstrate that HSV infection increases the risk of HIV acquisition. Incorporation of the antiretroviral tenofovir (TFV) along with the antiherpetic acyclovir (ACV) into combination intravaginal rings (IVRs) for sustained mucosal delivery of both compounds could lead to increased microbicide product adherence and efficacy compared with conventional vaginal formulations. A novel, dual-protection “pod IVR” platform developed in-house and delivering ACV and TFV was evaluated in rabbit and sheep models. The devices were safe and exhibited sustained release of both drugs independently and at controlled rates over the 28-day studies. Daily release rates were estimated based on residual drug content of the used devices: rabbits, 343 ± 335 μg day −1 (ACV) and 321 ± 207 μg day −1 (TFV); sheep, 174 ± 14 μg day −1 (ACV) and 185 ± 34 μg day −1 (TFV). Mean drug levels in sheep vaginal samples were as follows: secretions, 5.25 ± 7.31 μg ml −1 (ACV) and 20.6 ± 16.2 μg ml −1 (TFV); cervicovaginal lavage fluid, 118 ± 113 ng ml −1 (ACV) and 191 ± 125 ng ml −1 (TFV); tissue, 173 ng g −1 (ACV) and 93 ng g −1 (TFV). An in vitro-in vivo correlation was established for both drugs and will allow the development of future formulations delivering target levels for prophylaxis and therapy. These data suggest that the IVR based on the pod design has potential in the prevention of transmission of HIV-1 and other sexually transmitted pathogens.

This paper presents the design and development of experimental set-ups for the purpose of testing phase identification systems for power distribution networks. A series of hardware experiments and procedures were created within a laboratory environment at Drexel University to represent actual, distribution components and multiple operating conditions. These tests included multiple transformer connection types including Wye, Delta and Scott-T, distribution lines with high R/X ratios and loads of varying levels and power factor. Subsequently, studies were performed to validate the performance of an energized phase identification system based on synchrophasor technology.

Cheese ripening is a complex biochemical process driven by microbial communities composed of both eukaryotes and prokaryotes. Surface-ripened cheeses are widely consumed all over the world and are appreciated for their characteristic flavor. Microbial community composition has been studied for a long time on surface-ripened cheeses, but only limited knowledge has been acquired about its in situ metabolic activities. We applied metagenomic, metatranscriptomic and biochemical analyses to an experimental surface-ripened cheese composed of nine microbial species during four weeks of ripening. By combining all of the data, we were able to obtain an overview of the cheese maturation process and to better understand the metabolic activities of the different community members and their possible interactions. Furthermore, differential expression analysis was used to select a set of biomarker genes, providing a valuable tool that can be used to monitor the cheese-making process.

The present study extends prior work on the association between allergic rhinitis (AR) and common mental disorders by testing three related hypotheses: 1) that AR is associated with increased rates of depression and anxiety disorders in a large insured population, 2) comorbid AR, depression, and anxiety are associated with increased health and mental health expenditures, and 3) allergy treatment moderates the association between increased expenditures and comorbid AR, depression, and anxiety. Data are from MARKETSCAN ® , a large health care claims database of over 600,000 privately insured persons. Results indicate that AR is associated with higher rates of depression and anxiety disorder. Outpatient health care expenditures were increased by an average annual amount of $207 when AR and anxiety disorder were comorbid and $363 when AR and depression were comorbid. Finally, prescription treatment of AR moderated the increased expenditures associated with comorbidity.

Depression-related costs include a relatively large share of indirect costs. We describe the impact of antidepressant treatment on absenteeism among workers diagnosed and treated for depression. Monthly absenteeism counts from employers were summed in the 6 months before and after the initiation of antidepressant therapy in 630 workers treated for depression with a tricyclic antidepressant or a selective serotonin reuptake inhibitor (fluoxetine, sertraline, paroxetine). Monthly mean absenteeism was compared using pairwise t tests. Absenteeism increased before antidepressant initiation and decreased after the treatment began for all antidepressant cohorts. Absenteeism in the selective serotonin reuptake inhibitor cohorts decreased at similar rates for 4 months but was higher in the paroxetine cohort in months five and six after the treatment initiation. Our data suggest that alternative treatments for depression may have differential impact on indirect costs, but further research is warranted.

Background Depression is associated with high rates of relapse and recurrence during a patient's lifetime. Current guidelines regarding treatment recommend 4 to 9 months of continuation antidepressant therapy following remission of acute symptoms to allow more complete resolution of the episode. In this article, we test whether adherence to these recommendations reduces the likelihood of relapse or recurrence in a Medicaid population. Methods We used a Medicaid database covering 1989 through 1994. The sample consists of the 4052 adult patients who filled an antidepressant prescription at the time of an initial diagnosis of depression. These patients were followed up for up to 2 years. Timing and counts of antidepressant prescription claims are used to construct a proxy measure for adherence to guidelines. Relapse or recurrence is defined by evidence of a new episode requiring antidepressant treatment, hospital admission for depression, electroconvulsive therapy, emergency department visit for mental health, or attempted suicide. We used survival analysis to predict relapse or recurrence for each patient and to examine the effect of following treatment guidelines on relapse and recurrence. Results Approximately one fourth of the patients had a relapse or recurrence during their follow-up period. Factors that affect relapse and recurrence include comorbidities, race, and guideline adherence. Those who continued therapy with their initial antidepressant were least likely to experience relapse or recurrence; those who discontinued their antidepressant early were most likely to experience relapse or recurrence. Conclusion Adherence to depression treatment guidelines with an antidepressant that is likely to have continuous use by patients reduces the probability of relapse or recurrence.