bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and Feasibility of Integrating Yttrium-90 Radioembolization With Capecitabine-Temozolomide for Grade 2 Liver-Dominant Metastatic Neuroendocrine Tumors
Authors: Soulen Michael C. , van Houten Diana , Teitelbaum Ursina R. , Damjanov Nevena , Cengel Keith A. , Metz David C.
Published: July 2018

Objectives

An integrated protocol combining capecitibine-temozolomide with yttrium-90 radioembolization (CapTemY90) for liver-dominant grade 2 neuroendocrine tumors (NETs) was designed in the hope of achieving synergistic improvement in liver disease control with no more than additive toxicities. This report describes the feasibility and safety of this regimen.

Methods

Twenty-one patients with unresectable grade 2 NET liver-dominant metastases without contraindications to radioembolization or to CapTem initiated therapy with capecitabine 600 mg/m2 twice daily for 14 days and temozolomide 150 to 200 mg/m2 in 2 divided doses on days 10 to 14, with 14 days between cycles. During the first cycle, simulation angiography was performed. The dominant lobe was radioembolized on day 7 of the second cycle. In patients with bilobar disease, the other lobe was treated on day 7 of the third or fourth cycle.

Results

Nineteen of 21 patients completed the protocol. Adverse events were as expected. Objective response rate was 74% in the liver and 55% for extrahepatic tumor. Median progression-free survival was not reached. Progression-free survival at 3 years was 67%, with 74% progression-free in the liver.

Conclusions

CapTemY90 is feasible and safe for grade 2 NETs. Toxicities were additive. Oncologic outcomes suggest synergy.
Utility of Endoscopic Ultrasound-Guided Biopsy for Next-Generation Sequencing of Pancreatic Exocrine Malignancies
Authors: Larson Brent K. , Tuli Richard , Jamil Laith H. , Lo Simon K. , Deng Nan , Hendifar Andrew E.
Published: July 2018

Objectives

Endoscopic ultrasound-guided fine-needle biopsy and aspiration (EUS FNB/A) are the standard diagnostic tests for pancreatic malignancies. Oncologists increasingly use tumor genomic analysis for management. Adequacy of FNB/A tissue for next-generation sequencing (NGS) has not been evaluated. This study examined FNB/A and other biopsy types for features that might predict adequacy for NGS.

Methods

Seventy-six pancreatic exocrine malignancy biopsies submitted for NGS were assessed for adequacy, which was compared with other tumor/biopsy features.

Results

Twenty-two (29%) of 76 samples were inadequate, including 16 (30%) of 54 FNBs and 4 (57%) of 7 FNAs. Larger-gauge needles were associated with adequacy in all samples (P = 0.0047) and in FNBs (P = 0.05). Metastatic samples were more likely to be adequate for NGS compared with pancreatic samples (P = 0.0357). Percutaneous biopsies were more likely to be adequate than EUS-guided FNB/As, although this trend was not significant (P = 0.0558). Other tumor/biopsy characteristics were not associated with adequacy.

Conclusions

Endoscopic US FNA and FNB provided similar NGS adequacy rates. Metastatic lesions accessible by percutaneous biopsy may be preferable to EUS FNB/A of primary lesions for obtaining tissue for NGS. All biopsies, including EUS FNB, were more likely to be successful using larger-gauge needles.
Sustained Viral Response in Genotype 4 Chronic Hepatitis C Virus–infected Children and Adolescents Treated With Sofosbuvir/Ledipasvir
Authors: El‐Karaksy Hanaa , Mogahed Engy Adel , Abdullatif Hala , Ghobrial Carolyne , El‐Raziky Mona S. , El‐Koofy Nehal , El‐Shabrawi Mortada , Ghita Haytham , Baroudy Sherif , Okasha Sawsan
Published: July 2018

Objectives:

Recently, direct acting antivirals (DAAs), sofosbuvir (SOF) combined with ledipasvir (LED), were approved for treatment of hepatitis C virus (HCV)–infected children 12 years of age and older or weighting at least 35 kg for all HCV genotypes. The aim of this study was to assess the safety and efficacy of SOF/LED in genotype 4 HCV‐infected Egyptian children and adolescents.

Methods:

This observational study included 40 consecutive HCV‐infected children of age 12 to <18 years old or weighing >35 kg, both treatment‐naive and treatment‐experienced. All of the children were hepatitis B virus–negative and had normal renal functions and heart rate. Patients received oral, fixed‐dose combination tablet of SOF/LED (400 mg SOF, 90 mg LED [Harvoni]) once daily for 12 weeks. Potential side effects were recorded at weeks 4, 8, and 12 weeks of treatment. The study primary outcome was sustained virological response 12 weeks (SVR12) after end‐of‐treatment.

Results:

The study included 40 children and adolescents, 24 were boys (60%); their age ranged between 11.5 and 17.5 years (mean 13.9 ± 1.5). Baseline viral load ranged between 9630 and 24,600,000 IU/mL. HCV RNA became negative in 39 patients (97.5%) at 4 weeks and in all patients (100%) at weeks 8, 12, and SVR12. Asthenia was the commonest side effect, reported in 52.5% followed by headache in 47.5%.

Conclusions:

Treatment with all‐oral DAAs (SOF/LED) for 12 weeks was well tolerated in Egyptian children and adolescents infected with genotype 4 HCV, with 100% SVR12 and negligible side effects.
Serum Immunoglobulin A Levels Do Not Correlate With Liver Disease Severity in Pediatric Nonalcoholic Fatty Liver Disease
Authors: Mouzaki Marialena , Bramlage Kristin , Arce‐Clachar Ana Catalina , Xanthakos Stavra A.
Published: July 2018

Serum immunoglobulin A (IgA) is a biomarker of liver disease severity in adult nonalcoholic fatty liver disease (NAFLD). The objective of this study was to assess whether this is true in pediatric NAFLD. This was a retrospective study of children followed in the Steatohepatitis Center of a tertiary care center (2010–2017). Serum IgA levels, histology and biochemical markers of hepatocellular injury and metabolic dysregulation were collected. Of the 600 children with available serum IgA levels (mean age 14 ± 3 years, 62% boys, 80% non‐Hispanic), IgA was elevated in 4%. The group with elevated IgA levels was younger and had a greater representation of Hispanic ethnicity compared with those with normal or low IgA. Body mass index and aminotransferases were not different between the groups. Histology was available for 170 children and was not different in those with elevated, normal and low IgA. In contrast to adults, serum IgA is not a biomarker of liver disease severity in pediatric NAFLD.
Meaning-Centered Interventions for Patients With Advanced or Terminal Cancer
Authors: Kang Kyung-Ah , Han Suk-Jung , Lim Young-Sook , Kim Shin-Jeong
Published: July 2018

Background

For patients with advanced or terminal cancer undergoing hospice or palliative care, spiritual care based on meaning-centered intervention (MCI) has become an essential form of support.

Objective

The aim of this study was to characterize MCI systematically and the effectiveness of hospice and palliative care for patients with advanced or terminal cancer.

Methods

MEDLINE via PubMed, Cochrane Library CENTRAL, EMBASE, CINAHL, and several Korean electronic databases were searched from inception to May 2017. The RevMan 5.3 program of the Cochrane Library was used for data analysis.

Results

A meta-analysis was conducted of 10 controlled trials (6 randomized and 4 nonrandomized) featuring 623 patients with cancer. Meaning-centered interventions were compared with usual care control groups or other psychosocial interventions. The weighted average effect sizes across studies were −0.96 (P < .001, I
2 = 7%) for meaning in life, −0.37 (P = .002, I
2 = 0%) for spiritual well-being, −0.48 (P < .001, I
2 = 0%) for quality of life, −0.28 (P = .02, I
2 = 0%) for anxiety, and −0.31 (P = .02, I
2 = 17%) for physical symptoms.

Conclusion

Spiritual care based on MCI may help to improve the physical, psychosocial, and spiritual well-being of patients with advanced or terminal cancer.

Implication for Practice

Meaning-centered interventions could be a valuable way to enhance quality of life at the end stage for patients with advanced or terminal cancer.
Trying to Feel Normal Again: Early Survivorship for Adolescent Cancer Survivors
Authors: Walker Amy J. , Lewis Frances M. , Lin Yuting , Zahlis Ellen , Rosenberg Abby R.
Published: July 2018

Background

Despite knowing the potential medical consequences of cancer treatment, little is known about how adolescents cognitively and emotionally frame, process, and manage in the early survivorship period.

Objective

The specific aims were to describe the worries, perceived challenges, and ways of dealing with these issues for adolescent cancer survivors in the early period of survivorship.

Methods

Twenty-nine adolescent survivors (12–18 years) completed a semistructured interview. Inductive coding methods adapted from grounded theory were used to analyze the data.

Results

Seven domains and 18 categories organized the adolescent's experience with early posttreatment survivorship. The domains included getting back to school; relationships with parents, siblings, friends; feeling changed by the experience; and concerns about relapse.

Conclusions

This study contributes to our understanding of survivors' relationships with parents, siblings, and friends and survivors' models of the illness. Future studies are needed to understand how parents can help adolescents assume greater responsibility for their care, to understand what it is like for friends to have a peer with cancer and what behaviors by healthcare providers contribute to feelings of abandonment later in survivorship, and to better understand adolescent survivors' models of the illness and survivorship.

Implications for Practice

Study results suggest that nurses are in an ideal position to begin and to continue discussions with adolescent survivors about the adolescent's view of medical follow- up, its purpose and importance, and ways in which the adolescent can begin, early on, to engage in planning their own health during survivorship.
An Initial Study of Alexithymia and Its Relationship With Cognitive Abilities Among Mild Cognitive Impairment, Mild Alzheimer's Disease, and Healthy Volunteers
Authors: Smirni Daniela , Beadle Janelle N. , Paradiso Sergio
Published: July 2018

The present study examined the degree to which alexithymia is greater in mild Alzheimer's disease (AD) and mild cognitive impairment (MCI) relative to healthy volunteers (healthy comparison [HC]), and investigated relationships between alexithymia and cognition. Eighty-five participants (MCI = 30, AD = 21, HC = 34) underwent a comprehensive neuropsychological examination and completed the 20-item Toronto Alexithymia Scale (TAS-20). Relative to HC, MCI and AD reported greater alexithymia total scores and higher scores on the TAS factor difficulty in identifying feelings (DIF). The remaining two factors, difficulty in describing feelings (DDF) and externally oriented thinking showed no significant group differences. In MCI, TAS-20 and DIF were negatively correlated with working and long-term verbal memory. In AD, TAS-20 was negatively correlated with general cognition, attention, memory, and visual spatial constructive and executive abilities. Also in AD, DIF was negatively correlated with general cognition, memory, and executive abilities. The correlation between DIF and long-term verbal memory in both MCI and AD suggests a potential common mechanism for alexithymia in these neurocognitive disorders. Declines in verbal memory may hinder a patient's ability to recall an association between a given sensation and the episodic experience of that sensation, thus leading to difficulty identifying feelings, as measured by the DIF factor of the TAS-20.
Social Anxiety and Benign and Toxic Online Self-Disclosures
Authors: Molavi Parviz , Mikaeili Niloofar , Ghaseminejad Mohammad Ali , Kazemi Zhila , Pourdonya Misagh
Published: July 2018

This work aimed to explore the relationship between social anxiety with benign and toxic online self-disclosures with the mediating role of rejection sensitivity, self-regulation, and Internet addiction. In this study, 358 students who were active members of social networks at the Mohaghegh Ardabili University, Iran were evaluated in the form of a structural equation model. The results substantiated that social anxiety could explain 47% of the variance in benign online self-disclosure and 27% of toxic online self-disclosure with the mediating role of rejection sensitivity, self-regulation, and Internet addiction. It was found that people with high social anxiety had higher rejection sensitivity and lower self-regulation. Also, people with higher social anxiety had directly higher benign and toxic online self-disclosures. The results indicated that self-regulation did not have a direct impact on benign online self-disclosure; however, it had a direct negative impact on toxic online self-disclosure.
Emergency Department Documentation of Alleged Police Use of Excessive Force in Cases Where Formal Complaints Are Ultimately Filed
Authors: Strote Jared , Hickman Matthew J.
Published: July 2018

Background

Emergency physicians encounter patient concerns of police use of excessive force (UOEF). However, unlike other forms of potential assault, there are no guidelines for documentation of these encounters. Our objective was to examine the adequacy of emergency department documentation of injuries from police encounters where formal complaints of UOEF were later filed with the law enforcement agency.

Methods

A retrospective cohort design was used, identifying all citizen complaints of UOEF to a single police department in a 3-year period. Emergency department records associated with these encounters were then accessed and evaluated using standards for other forms of abuse and assault.

Results

Of 235 complaints, 33 (14.0%) presented to the emergency department within 7 days of the incident and were able to provide a history. For these subjects, 13 charts (39.4%) contained 3 or more of the 4 components thought to be necessary in cases of potential assault, and 11 (33.3%) contained documentation that should not be present: the guilt of the patient, subjective terminology by the provider, and/or documentation of law enforcement's description of the events as the only factual history. Of the total, 14 charts (42.4%) documented the patient's concern for UOEF.

Conclusions

In this limited study, documentation of encounters where patients later filed a formal complaint of UOEF by law enforcement did not meet the standards for other forms of assault and abuse, having the potential to impact both the citizens and officers involved. Further study is necessary to identify the best practice guidelines for emergency physicians when they encounter patients injured in police encounters.
Acute Pancreatitis Caused by Isolated Pancreatic Metastasis From Uterine Choriocarcinoma
Authors: Muktesh Gaurav , Mitra Suvradeep , Sinha Saroj K. , Dhaka Narendra , Saikia Uma N. , Sarma Phulen , Gulati Ajay , Samanta Jayanta , Kochhar Rakesh
Published: July 2018

Choriocarcinoma is an aggressive gestational trophoblastic neoplasia known for its widely metastatic potential. However, isolated pancreatic metastasis is an extremely rare occurrence and has not been documented in the English literature to the best of our knowledge. The metastatic deposits in the index case led to widespread hemorrhage and necrosis of the pancreatic parenchyma, causing severe acute pancreatitis. The patient succumbed to her illness before chemotherapy was administered. Thus, we present an autopsy case of a uterine choriocarcinoma with isolated pancreatic metastasis presenting as severe acute pancreatitis in a 27-yr-old woman following a molar pregnancy.
Defining Patient Safety Events in Inpatient Psychiatry
Authors: Marcus Steven C. , Hermann Richard C. , Cullen Sara Wiesel
Published: July 2018

Objectives

The past 20 years have seen the emergence of a national movement to improve hospital-based healthcare safety in the United States. However, much of the foundational work and subsequent research have neglected inpatient psychiatry. The aim of this article was to advance a comprehensive approach for conceptualizing patient safety in inpatient psychiatry as framed by an application of the Institute of Medicine patient safety framework.

Methods

This article develops a framework for characterizing patient safety in hospital-based mental health care. We discuss some of the conceptual and methodological issues related to defining what constitutes a patient safety event in inpatient psychiatry and then enumerate a comprehensive set of definitions of the types of safety events that occur in this setting.

Results

Patient safety events in inpatient psychiatry are broadly categorized as adverse events and medical errors. Adverse events are composed of adverse drug events and nondrug adverse events, including self-harm or injury to self, assault, sexual contact, patient falls, and other injuries. Medical errors include medication errors and nonmedication errors, such as elopement and contraband. We have developed clear definitions that would be appropriate for use in epidemiological studies of inpatient mental health treatment.

Conclusions

Psychiatry has not been an integral part of the national safety movement. As a first step toward breaching this chasm, we have considered how psychiatric events fit into the safety framework adopted across much of medicine. Patient safety should become a key part of inpatient psychiatry’s mission and pursued rigorously as the subject of research and intervention efforts.
Horizontal Maxillary Osteotomy Stability Using Mandibular Outer Cortex Bone Grafts in Patients With Cleft Lip and Palate
Authors: Zheng Yilue , Yin Ningbei , Jiang Chanyuan , Song Tao
Published: July 2018

Objective:

To investigate horizontal maxillary osteotomy stability after using bone grafts for the treatment of patients with unilateral cleft lip and palate (UCLP).

Design:

Retrospective cohort study.

Setting:

Plastic surgery hospital.

Patients:

Fifty-eight patients with UCLP and maxillary hypoplasia requiring a maxillary Le Fort I advancement of 6 to 9 mm.

Interventions:

The test group (TG) was comprised of 28 patients who underwent mandibular outer cortex bone grafting in the gaps created by a modified Le Fort I osteotomy. The control group (CG) was comprised of 30 patients who underwent a Le Fort I osteotomy without bone grafts.

Main Outcome Measures:

Maxillary horizontal advancement (recorded during the operation using a Vernier caliper) and horizontal relapse at 12 months after surgery (based on a manual cephalometric analysis of pre- and postoperative lateral teleradiographs).

Results:

In the TG, the mean maxillary horizontal advancement was 7.13 ± 0.7 mm (range: 6.01–8.23 mm), and the mean postoperative horizontal relapse was 25.07 ± 6.64%. In the CG, the mean maxillary horizontal advancement was 6.90 ± 0.55 mm (range: 6.05–7.39 mm), and the mean postoperative horizontal relapse was 24.89 ± 4.25%. There were no significant between-group differences in the mean horizontal relapses.

Conclusion:

The use of mandibular outer cortex bone grafts as physical barriers in patients with UCLP does not increase postoperative stability when the maxillary advancement is 6 to 9 mm.
Audiological Alterations in Patients With Cleft Palate
Authors: Rivelli Ramiro Adrian , Casadio Vanesa , Bennun Ricardo D.
Published: July 2018

Introduction:

Chronic otitis media with effusion (OME) is a recurrent complication, usually found in cleft palate patients.

Conductive hearing loss is the result of the Eustachian tube dysfunction caused by the absence of fusion and the altered insertion of the muscles of the secondary palate. It is also the consequence of an ineffective muscular reconstruction after primary cleft palate repair.

Methods:

This is a cohort study to compare 4 groups of patients born with isolated cleft lip (ICL), unilateral cleft lip/palate (UCLP), bilateral cleft lip/palate (BCLP), and isolated cleft palate (ICP), received in our hospital between June 2015 to September 2017, operated by the same surgeon, using the same surgical technique and protocol.

Complete cleft palate repair was performed, in average, at 10 months, and placement of ventilation tubes, if necessary, was made in the same operatory act.

After palate repair, primary or secondary hearing loss was checked, joint to the connection with the type of used ventilation tubes, recurrences and complications also were considered.

Results:

The study sample was integrated by 69 patients, 2 of 11 patients with ICL (18.18%), 30 of 34 patients with UCLP (88.23%), 17 of 19 patients with BCLP (89.47%), and 4 of 5 patients with ICP (80.00%) were diagnosed with OME requiring ventilation tubes at the time of surgery. It can be established that the average hearing loss in patients with diabolos in the postoperative period is 19.4 db and in those patients with T tubes it is 14.2 db, the difference being statistically significant (P < 0.05).

Conclusion:

Hearing improvement prior to language acquisition is essential for a proper speech development. Early trans tympanic tubes implantation during cleft palate repair contributes to a correct short-term ventilation of the middle ear, being the T tubes the best option.
Tetrahydrocannabinol/Cannabidiol Oromucosal Spray in Patients With Multiple Sclerosis: A Pilot Study on the Plasma Concentration-Effect Relationship
Authors: Contin Manuela , Mancinelli Luca , Perrone Alessandro , Sabattini Loredana , Mohamed Susan , Scandellari Cinzia , Foschi Matteo , Vacchiano Veria , Lugaresi Alessandra , Riva Roberto
Published: July 2018

Objectives

We aimed to assess the potential relationship between intrasubject 9-tetrahydrocannabinol/cannabidiol (THC/CBD) oromucosal spray plasma profiles and clinical effects elicited by subacute dosing in chronically treated patients with multiple sclerosis (MS).

Methods

The study design was pilot, single center, open, and prospective. The patients were challenged with a morning test dose of 2 THC/CBD sprays at a 15-minute interval. Venous blood samples were collected before the first spray administration and every 30 minutes after the second spray, until 240 minutes postdosing. Patients rated their spasticity by the Numerical Rating Scale (NRS) simultaneously with blood drawings. Postural and motor tests were performed before the first spray and 90 and 180 minutes thereafter.

Results

Twelve patients were recruited. Peak plasma concentrations of THC/CBD largely varied among patients, from 0.60 to 13.29 ng/mL for THC and 0.55 to 11.93 ng/mL for CBD. Time to peak plasma concentrations ranged from 150 to 240 minutes for THC and 90 to 240 minutes for CBD. Patients' NRS serial scores decreased after dosing, from a median value of 6 to 3.5 (P < 0.001). A significant inverse correlation was observed between median intrasubject repeated NRS scores and corresponding median values of both THC (P < 0.01) and CBD (P < 0.002) plasma concentrations. No significant effect of cannabinoids dosing could be appreciated according to posturographic and motor tests.

Conclusions

Our kinetic dynamic findings from THC/CBD oromucosal spray are the first obtained in real MS patients. Although preliminary, they suggest that subacute dosing might elicit a subjective clinically significant effect on MS-related spasticity, paralleling cannabinoids measurable plasma concentrations.
The merits of sustaining pneumococcal vaccination after transitioning from Gavi support – a modelling and cost-effectiveness study for Kenya
Authors: Ojal John , Griffiths Ulla , Hammitt Laura L. , Adetifa Ifedayo , Akech Donald , Tabu Collins , Scott Anthony G. , Flasche Stefan
Published: July 2018

Introduction

Many low income countries soon will need to consider whether to continue pneumococcal conjugate vaccine (PCV) use at full costs as they transition from Gavi support. Using Kenya as a case study we assessed the incremental cost-effectiveness of continuing PCV use.

Methods

We fitted a dynamic compartmental model of pneumococcal carriage to annual carriage prevalence surveys and invasive pneumococcal disease (IPD) incidence in Kilifi, Kenya, and predicted disease incidence and related mortality for either continuing PCV use beyond 2022, the start of Kenya’s transition from Gavi support, or its discontinuation. We calculated the costs per disability-adjusted-life-year (DALY) averted and associated prediction intervals (PI).

Results

We predicted that overall IPD incidence will increase by 93% (PI: 72% - 114%) from 8.5 in 2022 to 16.2 per 100,000 per year in 2032, if PCV use is discontinued. Continuing vaccination would prevent 15,355 (PI: 10,196–21,125) deaths and 112,050 (PI: 79,620– 130,981) disease cases during that time. Continuing PCV after 2022 will require an estimated additional US$15.6 million annually compared to discontinuing vaccination. The incremental cost per DALY averted of continuing PCV was predicted at $142 (PI: 85 - 252) in 2032.

Conclusion

Continuing PCV use is essential to sustain its health gains. Based on the Kenyan GDP per capita of $1445, and in comparison to other vaccines, continued PCV use at full costs is cost-effective. These arguments support an expansion of the vaccine budget, however, affordability may be a concern.

Funding

Funded by the Wellcome Trust.
Implementation of the Water Framework Directive: Lessons learned and future perspectives for an ecologically meaningful classification of the status of Greek lakes, Mediterranean region
Authors: Moustaka-Gouni Maria , Sommer Ulrich , Economou-Amilli Athena , Arhonditsis George B. , Katsiapi Matina , Papastergiadou Eva , Kormas Konstantinos A. , Vardaka Elisabeth , Karayanni Hera , Papadimitriou Theodoti
Published: July 2018

The enactment of the Water Framework Directive (WFD) initiated scientific efforts to develop reliable methods for comparing prevailing lake conditions againstreference(or non-impaired) states, using the state of a set biological elements. Drawing a distinction between impaired and natural conditions can be a challenging exercise, as it stipulates the robust delineation of reference conditions along with the establishment of threshold values for key environmental variables used as proxies for the degree of system impairment. Another important aspect is to ensure that water quality assessment is comparable among the different Member States. In this context, the present paper offers a constructive critique of the practices followed during the WFD implementation in Greece by pinpointing methodological weaknesses and knowledge gaps that undermine our ability to classify the ecological status of Greek lakes. One of the pillars of WDF is a valid lake typology that sets ecological standards transcending geographic regions and national boundaries. The national typology of Greek lakes has failed to take into account essential components (e.g. surface area, altitude, salinity). WFD compliance assessments based on descriptions of phytoplankton communities are oversimplified and as such should be revisited. Exclusion of most chroococcal species from the analysis of cyanobacteria biovolume in Greek lakes and most reservoirs in the Mediterranean Geographical Intercalibration Group (Greece, Spain, Portugal and Cyprus) is not consistent with the distribution of those taxa in lakes. Similarly, the total biovolume reference values and the indices used in their classification schemes reflect misunderstandings of WFD core principles. This hampers the comparability of ecological status across Europe and leads to quality standards that are too relaxed to provide an efficient target especially for the protection and management of Greek/transboundary lakes such as Lake Megali Prespa, one of the oldest lakes in Europe.
Systems analysis by mass cytometry identifies susceptibility of latent HIV-infected T cells to targeting of p38 and mTOR pathways
Authors: Fong Linda E. , Bass Victor L. , Spudich Serena , Miller-Jensen Kathryn
Published: July 2018

Efforts to cure HIV are hindered by viral persistence in latently infected memory CD4+ T cells. Targeting T cell death pathways dysregulated by HIV infection offers a novel approach for eradication of the latent reservoir. To identify potential therapeutic targets, we compared signaling and apoptosis in uninfected and latently infected primary cultured CD4+ central memory T cells by mass cytometry following T cell receptor stimulation. We found that HIV-infected cells were sensitized to activation of pro-apoptotic p38 kinase signaling via p53, and to inhibition of anti-apoptotic mTOR kinase signaling, even without HIV protein expression. Simultaneous targeting of p38 and mTOR kinases in resting CD4+ T cells from virally-suppressed HIV+ patientsex vivoreduced cell-associated HIV RNA and DNA. Our results demonstrate how systems biology approaches are useful for identifying novel therapeutic approaches to treat HIV latency, and further suggest that it may be possible to deplete latent HIV-infected T cells without viral reactivation.
Do We See Scale?
Authors: Linton Paul
Published: July 2018

The visual system is supposed to extract distance information from the environment in order to scale the size and distance of objects in the visual scene. The purpose of this article is to challenge this account in three stages: First, I identify three shortcomings of the literature on vergence as our primary cue to near distances. Second, I present the results from two experiments that control for these shortcomings, but at the cost of eradicating vergence and accommodation as effective distance cues (average gain of y = 0.161x + 38.64). Third, I argue that if all our cues to distance are either (a) ineffective (vergence; accommodation; motion parallax), (b) merely relative (angular size; diplopia), or (c) merely cognitive (familiar size; vertical disparity), then the visual system does not appear to extract absolute distance information, and we should be open to the possibility that vision functions without scale.
Phase-dependent suppression of beta oscillations in Parkinson’s disease patients
Authors: Holt Abbey B. , Kormann Eszter , Gulberti Alessandro , Pötter-Nerger Monika , McNamara Colin G. , Cagnan Hayriye , Little Simon , Köppen Johannes A. , Buhmann Carsten , Westphal Manfred , Gerloff Christian , Engel Andreas K. , Brown Peter , Hamel Wolfgang , Moll Christian K.E. , Sharott Andrew
Published: July 2018

Synchronized oscillations within and between brain areas facilitate normal processing, but are often amplified in disease. A prominent example is the abnormally sustained beta-frequency (~20Hz) oscillations recorded from the cortex and subthalamic nucleus of Parkinson’s Disease patients. Computational modelling suggests that the amplitude of such oscillations could be modulated by applying stimulation at a specific phase. Such a strategy would allow selective targeting of the oscillation, with relatively little effect on other activity parameters. Here we demonstrate in awake, parkinsonian patients undergoing functional neurosurgery, that electrical stimulation arriving on consecutive cycles of a specific phase of the subthalamic oscillation can suppress its amplitude and coupling to cortex. Stimulus-evoked changes in spiking did not have a consistent time course, suggesting that the oscillation was modulated independently of net output. Phase-dependent stimulation could thus be a valuable strategy for treating brain diseases and probing the function of oscillations in the healthy brain.
A global genomic approach uncovers novel components for twitching motility-mediated biofilm expansion in Pseudomonas aeruginosa
Authors: Nolan Laura M. , Whitchurch Cynthia B. , Barquist Lars , Katrib Marilyn , Boinett Christine J. , Mayho Matthew , Goulding David , Charles Ian G. , Filloux Alain , Parkhill Julian , Cain Amy K.
Published: July 2018

Pseudomonas aeruginosa is an extremely successful pathogen able to cause both acute and chronic infections in a range of hosts, utilizing a diverse arsenal of cell-associated and secreted virulence factors. A major cell-associated virulence factor, the Type IV pilus (T4P), is required for epithelial cell adherence and mediates a form of surface translocation termed twitching motility, which is necessary to establish a mature biofilm and actively expand these biofilms. P. aeruginosa twitching motility-mediated biofilm expansion is a coordinated, multicellular behaviour, allowing cells to rapidly colonize surfaces, including implanted medical devices. Although at least 44 proteins are known to be involved in the biogenesis, assembly and regulation of the T4P, with additional regulatory components and pathways implicated, it is unclear how these components and pathways interact to control these processes. In the current study, we used a global genomics-based random-mutagenesis technique, transposon directed insertion-site sequencing (TraDIS), coupled with a physical segregation approach, to identify all genes implicated in twitching motility-mediated biofilm expansion in P. aeruginosa. Our approach allowed identification of both known and novel genes, providing new insight into the complex molecular network that regulates this process in P. aeruginosa. Additionally, our data suggests a differential effect on twitching motility by flagellum components based upon their cellular location. Overall the success of our TraDIS approach supports the use of this global genomic technique for investigating virulence genes in bacterial pathogens.
Adaptation of ant supercolony behavior to solve route assignment problem in integers
Authors: Idres Lahna , Radjef Mohammed Said
Published: July 2018

Purpose

Until now, the algorithms used to compute an equilibrate route assignment do not return an integer solution. This disagreement constitutes a non-negligible drawback. In fact, it is shown in the literature that a fractional solution is not a good approximation of the integer one. The purpose of this paper is to find an integer route assignment.

Design/methodology/approach

The static route assignment problem is modeled as an asymmetric network congestion game. Then, an algorithm inspired from ant supercolony behavior is constructed, in order to compute an approximation of the Pure Nash Equilibrium (PNE) of the considered game. Several variants of the algorithm, which differ by their initializing steps and/or the kind of the provided algorithm information, are proposed.

Findings

An evaluation of these variants over different networks is conduced and the obtained results are encouraging. Indeed, the adaptation of ant supercolony behavior to solve the problem under consideration shows interesting results, since most of the algorithm’s variants returned high-quality approximation of PNE in more than 91 percent of the treated networks.

Originality/value

The asymmetric network congestion game is used to model route assignment problem. An algorithm with several variants inspired from ant supercolony behavior is developed. Unlike the classical ant colony algorithms where there is one nest, herein, several nests are considered. The deposit pheromone of an ant from a given nest is useful for the ants of the other nests.
Research on coordination mechanism for fresh agri-food supply chain with option contracts
Authors: Zhou Linan , Zhou Gengui , Qi Fangzhong , Li Hangying
Published: July 2018

Purpose

This paper aims to develop a coordination mechanism that can be applied to achieve the channel coordination and information sharing simultaneously in the fresh agri-food supply chain with uncertain demand. It seeks to elucidate how the producer can use an option contract to transfer the risk caused by uncertain demand, impel the retailer to share demand information and improve the performance of supply chain.

Design/methodology/approach

An option contract model based on the basic model of fresh agri-food supply chain is introduced to compare the production, profit, risk and information sharing condition of the supply chain in different cases. In addition, a case study focusing on the sale of autumn peaches produced by a local producer is investigated, which provides evidence of the applicability of the authors’ approach.

Findings

The optimal option contract can help the supply chain achieve channel coordination and reach Pareto improvement. In the meantime, such a contract will encourage the retailer to share market demand information with producer spontaneously and help maintain the strategic cooperation between two parties.

Research limitations/implications

This paper considers a single-producer, single-retailer system and both of them are risk neutral.

Practical implications

Presented results can be used as suggestions for improving the contract design of fresh agri-food supply chain in China and can also provide references for other countries with similar experiences as China in fresh agri-food production.

Originality/value

This research introduces the option contract into fresh agri-food supply chain and takes information sharing and the risk caused by uncertain demand into consideration.
Impact of processing temperature on production of milk protein permeate during microfiltration of skim or whole milk
Authors: Jarto Iswandi , Lucey John A , Smith Karen E
Published: July 2018

Microfiltration of skim or whole milk was compared at two processing temperatures (5 and 13 °C) and several weight concentration factors (WCFs). Permeate flux for whole milk was slightly lower than flux for skim milk at both temperatures and all WCFs due to its higher viscosity. Following the initial start‐up period, permeate flux was constant for either skim or whole milk processed at constant conditions of a WCF of 2 and 13 °C for 6 h. The concentration of whey proteins in permeate was similar for both skim and whole milk. Whole milk could be used for the production of milk permeate.
Debt Contract Enforcement and Conservatism: Evidence from a Natural Experiment
Authors: AGHAMOLLA CYRUS , LI NAN
Published: July 2018

This study provides evidence that the use of conservative accounting in debt contracting depends on the enforceability of the contract. To test the effect of debt contract enforcement on borrowers' timely loss recognition, we exploit the staggered introduction of enhanced debt contract enforcement in Indian states as a natural experiment, where the implementation of the enforcement is exogenous to the accounting choices and borrowing behavior of firms. The main results show that enhanced enforcement has a significant positive effect on the timeliness of loss recognition of borrowing firms. We find that the effect is strongest for firms that increased their overall borrowing and for firms with high levels of tangible assets, consistent with a collateral‐based explanation. This study also provides causal evidence that firms adopt conservative accounting due to lenders' demand.
Effects of insect infestation on rodent‐mediated dispersal of Quercus aliena: results from field and enclosure experiments
Authors: ZHANG Bo , CHEN Xiaoning , STEELE Michael A. , LI Jingang , CHANG Gang
Published: July 2018

Rodents influence plant establishment and regeneration by functioning as both seed predators and dispersers. However, these rodent–plant interactions can vary significantly due to various environmental conditions and the activity of other insect seed predators. Here, we use a combination of both field and enclosure (i.e. individual cage and semi‐natural enclosure) experiments, to determine whether rodents can distinguish sound seeds from those infested with insects. We also demonstrate how such responses to insects are influenced by food abundance and other environmental factors. We presented rodents with 2 kinds of Quercus aliena seeds (sound and insect‐infested seeds) in a subtropical forest in the Qinling Mountains, central China, from September to November of 2011 to 2013. The results showed that rodents preferred to hoard and eat sound seeds than infested seeds in the field and semi‐natural enclosure, while they preferred to eat infested seeds over sound seeds in the individual cages. In addition, both hoarding and eating decisions were influenced by food abundance. Rodents hoarded more sound seeds in years of high food abundance while they consumed more acorns in years of food shortage. Compared with field results, rodents reduced scatter‐hoarding behavior in semi‐natural enclosures and ate more insect‐infested seeds in smaller individual cages. These results further confirm that rodents distinguish infested seeds from non‐infested seeds but demonstrate that this behavior varies with conditions (i.e. environment and food abundance). We suggest that such interactions will influence the dispersal and natural regeneration of seeds as well as predation rates on insect larvae.
Stressful living in lower‐quality habitats? Body mass, feeding behavior and physiological stress levels in wild wood mouse populations
Authors: NAVARRO‐CASTILLA Álvaro , BARJA Isabel
Published: July 2018

Wild populations are continuously subjected to changes in environmental factors that pose different challenges. Body condition and hormones have been commonly used as health indicators due to their potential correlation with fitness. In the present study, we analyzed whether habitats of different quality influenced body mass, food intake and physiological stress levels in wild wood mice (Apodemus sylvaticus). Field work was seasonally carried out in Holm oak woods and pine forests in central Spain. A total of 93 wood mice from 4 different populations (2 per habitat type) were live‐trapped. From each captured individual we noted body mass and food intake, measured as the amount of bait remaining in each trap. The physiological stress levels were measured non‐invasively in collected fresh feces by quantifying fecal corticosterone metabolites (FCM) with a 5a‐pregnane‐3ß,11ß, 21‐triol‐20‐one enzyme immunoassay. Wood mice abundances decreased from spring to summer, were higher in Holm oak woods than in pine forests and also resulted in different age‐class distribution between both habitats. Individuals inhabiting pine forests showed a lower body mass and increased food intake, probably because of the comparatively lower food quality and availability in this habitat. Furthermore, these individuals showed increased physiological stress levels, likely due to the lower quality habitat in relation to both food and vegetation cover availability. Overall, besides affecting local wood mouse abundance, our study underscores the effect of habitat quality on body mass, food intake and the endocrine stress response. Considering the wood mouse's pivotal position in ecosystems, these results could help in the understanding of environmental traits hampering the viability of wild populations.
Economically Motivated Food Fraud and Adulteration in Brazil: Incidents and Alternatives to Minimize Occurrence
Authors: Tibola Casiane Salete , da Silva Simone Alves , Dossa Alvaro Augusto , Patrício Diego Inácio
Published: July 2018

Brazil is one of the world's largest food producers. Adulteration of foods is often reported and represent an important potential threat to food safety. Because of this, reduction of the vulnerability of foods to adulteration is of high priority to Brazil. This study analyzes economically motivated food fraud and adulterations in Brazil between 2007 and 2017, based on academic journal reports. In addition, alternatives are proposed to minimize these incidents through good practices, traceability systems and the development of methods to detect food fraud and adulteration. Complex supply chains for foods of animal origin, such as milk and dairy products, were the main targets of food fraud and adulterations. Other products prone to fraudulent activities were vegetable oils, especially olive oil, which are high value products. Meat and fish, as well as their respective by‐products, were also involved in some food fraud and adulteration, especially substitution. Cases of extraneous ingredient addition were also reported in the coffee and tea sectors. Comprehensive food fraud and adulteration prevention requires the enforcement of regulatory systems, increased sampling and monitoring, training of food producers and handlers, and development of precise, rapid, and cost‐effective methods of fraud detection. The availability of robust methods to identify the chemical constituents of foods could be a decisive step, both to detect and prevent fraud in producer countries and to open up new markets to these products. The results of this study can be used to analyze food safety risks and prioritize target areas for food research and policy‐making in order to enforce food safety regulations in Brazil.

Practical Application

A food fraud and adulteration review was conducted based on scientific literature in Brazil. Milk and its products were the main targets of food fraud and adulterations. Food fraud and adulteration causes and suggestions for good practice are presented. The results can be used to analyze food safety and protect consumer rights.
Cyanobacterial blooms in oil‐contaminated subtidal sediments revealed by integrated approaches
Authors: Xie Cuixiao , Sun Kaikai , Zhang Kai , Sun Yongge , Lu Zhenmei
Published: July 2018

Cyanobacteria are important primary producers on the surface of oceans and are susceptible to oil spills. However, their tolerance to oil and their roles in the bioremediation of crude oil remain elusive. We analysed the response of microbial communities to a simulated oil spill in estuarine sediment microcosms under a series of oil concentrations (0, 25, 125, and 250 g kg−1 dry wt.). Cyanobacterial blooms only occurred on the sediment surface in the low oil (LO, 25 g kg−1 dry wt.) group, and cyanobacteria grew from very small amounts to enriched levels according to an internal mechanism. The dominant phylotypes enriched in the oil‐contaminated sediments on day 35 were Leptolyngbya, Oscillatoria, Arthrospira (Spirulina), Geitlerinema and Cyanothece, and the majority were capable of fixing nitrogen. Gammaproteobacterial blooms occurred during the early stage, and Oceanospirillales dominated the sediment surface. The annotation of unassembled metatranscriptomic data revealed an increase in nitrogen metabolism, particularly photosynthesis (antenna proteins) during the later stage, together with depletion of fatty acid metabolism. In summary, high concentrations of crude oil are toxic to cyanobacteria but can facilitate the emergence of cyanobacterial aggregation at low concentrations (crude oil concentration < 25 g kg−1 dry wt.).
Mammalian target of rapamycin complex 1 and its downstream effector collapsin response mediator protein‐2 drive reinstatement of alcohol reward seeking
Authors: Ben Hamida Sami , Laguesse Sophie , Morisot Nadege , Park Jong‐Hyun , Phuamluong Khanhky , Berger Anthony L. , Park Ki Duk , Ron Dorit
Published: July 2018

Alcohol use disorder is a chronic relapsing disease. Maintaining abstinence represents a major challenge for alcohol‐dependent patients. Yet the molecular underpinnings of alcohol relapse remain poorly understood. In the present study, we investigated the potential role of the mammalian target of rapamycin complex 1 (mTORC1) in relapse to alcohol‐seeking behavior by using the reinstatement of a previously extinguished alcohol conditioned place preference (CPP) response as a surrogate relapse paradigm. We found that mTORC1 is activated in the nucleus accumbens shell following alcohol priming‐induced reinstatement of alcohol place preference. We further report that the selective mTORC1 inhibitor, rapamycin, abolishes reinstatement of alcohol place preference. Activation of mTORC1 initiates the translation of synaptic proteins, and we observed that reinstatement of alcohol CPP is associated with increased protein levels of one of mTORC1's downstream targets, collapsin response mediator protein‐2 (CRMP2), in the nucleus accumbens. Importantly, the level of mTORC1 activation and CRMP2 expression positively correlate with the CPP score during reinstatement. Finally, we found that systemic administration of the CRMP2 inhibitor, lacosamide, attenuates alcohol priming‐induced reinstatement of CPP. Together, our results reveal that mTORC1 and its downstream target, CRMP2, contribute to mechanisms underlying reinstatement of alcohol reward seeking. Our results could have important implications for the treatment of relapse to alcohol use and position the Food and Drug Administration approved drugs, rapamycin and lacosamide, for the treatment of alcohol use disorder.