bluuebunny/crossref_metadata_2025 huggingface dataset:
Payback time? Influence of having children on mortality in old age
Authors: Modig K , Talbäck M , Torssander J , Ahlbom A
Published: March 2017

Background

It is known that parents have lower mortality than childless individuals. Support from adult children to ageing parents may be of importance for parental health and longevity. The aim of this study was to estimate the association between having a child and the risk of death, and to examine whether the association increased at older ages when health starts to deteriorate and the need of support from a family member increases.

Methods

In this nationwide study, all men and women (born between 1911 and 1925 and residing in Sweden), as well as their children, were identified in population registers and followed over time. Age-specific death risks were calculated for each calendar year for individuals having at least one child and for individuals without children. Adjusted risk differences and risk ratios were estimated.

Results

Men and women having at least one child experienced lower death risks than childless men and women. At 60 years of age, the difference in life expectancy was 2 years for men and 1.5 years for women. The absolute differences in death risks increased with parents' age and were somewhat larger for men than for women. The association persisted when the potential confounding effect of having a partner was taken into account. The gender of the child did not matter for the association between parenthood and mortality.

Conclusions

Having children is associated with increased longevity, particularly in an absolute sense in old age. That the association increased with parents' age and was somewhat stronger for the non-married may suggest that social support is a possible explanation.
Enhancing the diagnosis of fabry disease in cardiology with a targeted information: a before–after control–impact study
Authors: Savary Anne-Louise , Morello Remy , Brasse-Lagnel Carole , Milliez Paul , Bekri Soumeya , Labombarda Fabien
Published: March 2017

Background

Cardiac complications in Fabry disease are frequent and dominated by a high frequency of left ventricular hypertrophy; therefore, cardiologists may have an essential role in screening for this disease. Providing cardiologists with targeted information on Fabry disease would be valuable and could reduce both diagnostic and therapeutic delays. The aim of this study was to evaluate the efficiency of such strategy for Fabry screening.

Methods

We conducted a before–after control–impact study by comparing observations made before and after targeted information on Fabry disease among cardiologists. The information on Fabry disease consisted of (1) an educational booklet, (2) oral information and (3) screening kits. The programme was evaluated at the end of a 12-month study period.

Results

Forty-two cardiologists participated to this study. None of them had conducted screening test and new diagnostic for Fabry disease in the 3 years prior the information. After the information, screening with dried blood spots was performed in 55 patients (ranged 18–77 years, men: 39) with cardiac monitoring for supposed sarcomeric hypertrophic cardiomyopathy (n=41) or unexplained left ventricular hypertrophy (n=14) from January 2015 to January 2016. Two new cases of Fabry disease were diagnosed (3.4%) in two men (ages 58 and 51 years). The information was deemed relevant in both content and structure and was deemed useful for everyday practice.

Conclusion

Cardiologists valued the targeted information on Fabry disease. This information had a direct clinical impact by allowing the diagnosis of two new families with Fabry disease.
Symmetrical and difunctional substituted cobalt phthalocyanines with benzoic acids fragments: Synthesis and catalytic activity
Authors: Vashurin Artur , Maizlish Vladimir , Kuzmin Ilya , Znoyko Serafima , Morozova Anastasiya , Razumov Mikhail , Koifman Oscar
Published: March 2017

Difunctional and symmetric phthalonitriles were synthesized by nucleophilic substitution of brome and nitro-group in 4-bromo-5-nitro-phthalonitrile for residues 4-amino-, 4-hydroxyl- and 4-sulfanyl benzoic acid. Symmetrical and difunctional substituted cobalt phthalocyanines were obtained by template synthesis based on mentioned phthalonitriles. Their spectral properties and catalytic activity in aerobic oxidation of sodium [Formula: see text],[Formula: see text]-carbomoditiolate were investigated.
Security in Automotive Networks
Authors: Mundhenk Philipp , Paverd Andrew , Mrowca Artur , Steinhorst Sebastian , Lukasiewycz Martin , Fahmy Suhaib A. , Chakraborty Samarjit
Published: March 2017

With the increasing amount of interconnections between vehicles, the attack surface of internal vehicle networks is rising steeply. Although these networks are shielded against external attacks, they often do not have any internal security to protect against malicious components or adversaries who can breach the network perimeter. To secure the in-vehicle network, all communicating components must be authenticated, and only authorized components should be allowed to send and receive messages. This is achieved through the use of an authentication framework. Cryptography is widely used to authenticate communicating parties and provide secure communication channels (e.g., Internet communication). However, the real-time performance requirements of in-vehicle networks restrict the types of cryptographic algorithms and protocols that may be used. In particular, asymmetric cryptography is computationally infeasible during vehicle operation.

In this work, we address the challenges of designing authentication protocols for automotive systems. We present Lightweight Authentication for Secure Automotive Networks (LASAN), a full lifecycle authentication approach. We describe the core LASAN protocols and show how they protect the internal vehicle network while complying with the real-time constraints and low computational resources of this domain. By leveraging the fixed structure of automotive networks, we minimize bandwidth and computation requirements. Unlike previous work, we also explain how this framework can be integrated into all aspects of the automotive product lifecycle, including manufacturing, vehicle maintenance, and software updates. We evaluate LASAN in two different ways: First, we analyze the security properties of the protocols using established protocol verification techniques based on formal methods. Second, we evaluate the timing requirements of LASAN and compare these to other frameworks using a new highly modular discrete event simulator for in-vehicle networks, which we have developed for this evaluation.
Representative Families of Product Families
Authors: Fomin Fedor V. , Lokshtanov Daniel , Panolan Fahad , Saurabh Saket
Published: March 2017

A subfamily
F′
of a set family
F
is said to
q
-
represent
F
if for every
A
∈
F
and
B
of size
q
such that
A
∩
B
= ∅ there exists a set
A′
∈
F′
such that
A′
∩
B
= ∅. Recently, we provided an algorithm that, for a given family
F
of sets of size
p
together with an integer
q
, efficiently computes a
q
-representative family
F′
of
F
of size approximately (p+q p). In this article, we consider the efficient computation of
q
-representative families for
product
families
F
. A family
F
is a product family if there exist families
A
and
B
such that
F
= {
A
, ∪,
B
:
A
∈
A
,
B
∈
B
,
A
, ∩,
B
= ∅}. Our main technical contribution is an algorithm that, given
A
,
B
and
q
, computes a
q
-representative family
F′
of
F
. The running time of our algorithm is
sublinear
in |
F
| for many choices of
A
,
B
, and
q
that occur naturally in several dynamic programming algorithms. We also give an algorithm for the computation of
q
-representative families for product families
F
in the more general setting where
q
-representation also involves independence in a matroid in addition to disjointness. This algorithm considerably outperforms the naive approach where one first computes
F
from
A
and
B
and then computes the
q
-representative family
F′
from
F
.

We give two applications of our new algorithms for computing
q
-representative families for product families. The first is a 3.8408

k

n

O
(1)

deterministic algorithm for the M
ultilinear
M
onomial
D
etection
(
k
-M
l
D) problem. The second is a significant improvement of deterministic dynamic programming algorithms for “connectivity problems” on graphs of bounded treewidth.
Phenylalanine isotope pulse method to measure effect of sepsis on protein breakdown and membrane transport in the pig
Authors: Ten Have Gabriella A. M. , Engelen Mariëlle P. K. J. , Wolfe Robert R. , Deutz Nicolaas E. P.
Published: March 2017

The primed-continuous (PC) phenylalanine (Phe) stable isotope infusion methodology is often used as a proxy for measuring whole body protein breakdown (WbPB) in sepsis. It is unclear if WbPB data obtained by an easy-to-use single IV Phe isotope pulse administration (PULSE) are comparable to those by PC. Compartmental modeling with PULSE could provide us more insight in WbPB in sepsis. Therefore, in the present study, we compared PULSE with PC as proxy for WbPB in an instrumented pig model with Pseudomonas aeruginosa-induced severe sepsis (Healthy: n = 9; Sepsis: n = 13). Seventeen hours after sepsis induction, we compared the Wb rate of appearance (WbRa) of Phe obtained by PC (L-[ ring-13C6]Phe) and PULSE (L-[15N]Phe) in arterial plasma using LC-MS/MS and (non)compartmental modeling. PULSE-WbRawas highly correlated with PC-WbRa( r = 0.732, P < 0.0001) and WbPB ( r = 0.897, P < 0.0001) independent of the septic state. PULSE-WbRawas 1.6 times higher than PC-WbRa( P < 0.001). Compartmental and noncompartmental PULSE modeling provide comparable WbRavalues, although compartmental modeling was more sensitive. WbPB was elevated in sepsis (Healthy: 3,378 ± 103; Sepsis: 4,333 ± 160 nmol·kg BW−1·min−1, P = 0.0002). With PULSE, sepsis was characterized by an increase of the metabolic shunting (Healthy: 3,021 ± 347; Sepsis: 4,233 ± 344 nmol·kg BW−1·min−1, P = 0.026). Membrane transport capacity was the same. Both PC and PULSE methods are able to assess changes in WbRaof plasma Phe reflecting WbPB changes with high sensitivity, independent of the (patho)physiological state. The easy-to-use (non)compartmental PULSE reflects better the real WbPB than PC. With PULSE compartmental analysis, we conclude that the membrane transport capacity for amino acids is not compromised in severe sepsis.
Oxygen delivery and the restoration of the muscle energetic balance following exercise: implications for delayed muscle recovery in patients with COPD
Authors: Layec Gwenael , Hart Corey R. , Trinity Joel D. , Kwon Oh-Sung , Rossman Matthew J. , Broxterman Ryan M. , Le Fur Yann , Jeong Eun-Kee , Richardson Russell S.
Published: March 2017

Patients with chronic obstructive pulmonary disease (COPD) experience a delayed recovery from skeletal muscle fatigue following exhaustive exercise that likely contributes to their progressive loss of mobility. As this phenomenon is not well understood, this study sought to examine postexercise peripheral oxygen (O2) transport and muscle metabolism dynamics in patients with COPD, two important determinants of muscle recovery. Twenty-four subjects, 12 nonhypoxemic patients with COPD and 12 healthy subjects with a sedentary lifestyle, performed dynamic plantar flexion exercise at 40% of the maximal work rate (WRmax) with phosphorus magnetic resonance spectroscopy (31P-MRS), near-infrared spectroscopy (NIRS), and vascular Doppler ultrasound assessments. The mean response time of limb blood flow at the offset of exercise was significantly prolonged in patients with COPD (controls: 56 ± 27 s; COPD: 120 ± 87 s; P < 0.05). In contrast, the postexercise time constant for capillary blood flow was not significantly different between groups (controls: 49 ± 23 s; COPD: 51 ± 21 s; P > 0.05). The initial postexercise convective O2delivery (controls: 0.15 ± 0.06 l/min; COPD: 0.15 ± 0.06 l/min) and the corresponding oxidative adenosine triphosphate (ATP) demand (controls: 14 ± 6 mM/min; COPD: 14 ± 6 mM/min) in the calf were not significantly different between controls and patients with COPD ( P > 0.05). The phosphocreatine resynthesis time constant (controls: 46 ± 20 s; COPD: 49 ± 21 s), peak mitochondrial phosphorylation rate, and initial proton efflux were also not significantly different between groups ( P > 0.05). Therefore, despite perturbed peripheral hemodynamics, intracellular O2availability, proton efflux, and aerobic metabolism recovery in the skeletal muscle of nonhypoxemic patients with COPD are preserved following plantar flexion exercise and thus are unlikely to contribute to the delayed recovery from exercise in this population.
Nonreciprocal homeostatic compensation in Drosophila potassium channel mutants
Authors: Kim Eugene Z. , Vienne Julie , Rosbash Michael , Griffith Leslie C.
Published: March 2017

Homeostatic control of intrinsic excitability is important for long-term regulation of neuronal activity. In conjunction with many other forms of plasticity, intrinsic homeostasis helps neurons maintain stable activity regimes in the face of external input variability and destabilizing genetic mutations. In this study, we report a mechanism by which Drosophila melanogaster larval motor neurons stabilize hyperactivity induced by the loss of the delayed rectifying K+ channel Shaker cognate B ( Shab), by upregulating the Ca2+-dependent K+ channel encoded by the slowpoke ( slo) gene. We also show that loss of SLO does not trigger a reciprocal compensatory upregulation of SHAB, implying that homeostatic signaling pathways utilize compensatory pathways unique to the channel that was mutated. SLO upregulation due to loss of SHAB involves nuclear Ca2+ signaling and dCREB, suggesting that the slo homeostatic response is transcriptionally mediated. Examination of the changes in gene expression induced by these mutations suggests that there is not a generic transcriptional response to increased excitability in motor neurons, but that homeostatic compensations are influenced by the identity of the lost conductance.

NEW & NOTEWORTHY The idea that activity-dependent homeostatic plasticity is driven solely by firing has wide credence. In this report we show that homeostatic compensation after loss of an ion channel conductance is tailored to identity of the channel lost, not its properties.
In vivo optogenetic activation of Nav1.8+ cutaneous nociceptors and their responses to natural stimuli
Authors: Uhelski Megan L. , Bruce Daniel J. , Séguéla Philippe , Wilcox George L. , Simone Donald A.
Published: March 2017

Optogenetic methods that utilize expression of the light-sensitive protein channelrhodopsin-2 (ChR2) in neurons have enabled selective activation of specific subtypes or groups of neurons to determine their functions. Using a transgenic mouse model in which neurons natively expressing Nav1.8 (a tetrodotoxin-resistant voltage-gated sodium channel) also express the light-gated channel ChR2, we have been able to determine the functional properties of Nav1.8-expressing cutaneous nociceptors of the glabrous skin in vivo. Most (44 of 53) of the C-fiber nociceptors isolated from Nav1.8-ChR2+ mice were found to be responsive to blue (470 nm) light. Response characteristics, including conduction velocity and responses to mechanical stimuli, were comparable between nociceptors isolated from Nav1.8-ChR2+ and control mice. Interestingly, while none of the non–light-responsive C-fibers were sensitive to heat or cold, nearly all (77%) light-sensitive fibers were excited by mechanical and thermal stimuli, suggesting that Nav1.8 is predominantly expressed by C-fiber nociceptors that are responsive to multiple stimulus modalities. The ability to activate peripheral nociceptors with light provides a method of stimulation that is noninvasive, does not require mechanical interruption of the skin, and accesses receptive fields that might be difficult or impossible to stimulate with standard stimuli while allowing repeated stimulation without injuring the skin.

NEW & NOTEWORTHY Transgenic mice that express the blue light-sensitive protein channelrhodopsin2 (ChR2) in nociceptive nerve fibers that contain voltage-gated sodium channel Nav1.8 were used to determine functional properties of these afferent fibers. Electrophysiological recordings in vivo revealed that most nociceptive fibers that possess Nav1.8 are C-fiber nociceptors that respond to multiple stimulus modalities. Furthermore, responses evoked by blue light stimulation were comparable to those elicited by noxious mechanical, heat, and cold stimuli.
No consistent effect of cerebellar transcranial direct current stimulation on visuomotor adaptation
Authors: Jalali Roya , Miall R. Chris , Galea Joseph M.
Published: March 2017

Cerebellar transcranial direct current stimulation (ctDCS) is known to enhance motor adaptation and thus holds promise as a therapeutic intervention. However, understanding the reliability of ctDCS across varying task parameters is crucial. To examine this, we investigated whether ctDCS enhanced visuomotor adaptation across a range of varying task parameters. We found ctDCS to have no consistent effect on visuomotor adaptation, questioning the validity of using ctDCS within a clinical context.
A Discrete Model for Nonlinear Vibration of Beams Resting on Various Types of Elastic Foundations
Authors: Khnaijar A. , Benamar R.
Published: March 2017

This paper presents a discrete physical model to approach the problem of nonlinear vibrations of beams resting on elastic foundations. The model consists of a beam made of several small bars, evenly spaced. The bending stiffness is modeled by spiral springs, and the Winkler soil stiffness is modeled using linear vertical springs. Concentrated masses, presenting the inertia of the beam, are located at the bar ends. Finally, the nonlinear effect is presented by the axial forces in the bars, assumed to behave as longitudinal springs, due to the change in their length induced by the Pythagorean Theorem. This model has the advantage of simplifying parametric studies, because of its discrete nature, allowing any modification in the mass matrix, the stiffness matrix, and the nonlinearity tensor to be made separately. Therefore, once the model is established, various practical applications may be performed without the need of going through all the formulation again. The study of the nonlinear behavior makes the solution of the movement equation rise in complexity. By considering this discrete model and using the linearization method, one can achieve an idealized approach to this nonlinear problem and obtain quite easily approximate solutions.
A DDoS Attack Detection Method Based on Hybrid Heterogeneous Multiclassifier Ensemble Learning
Authors: Jia Bin , Huang Xiaohong , Liu Rujun , Ma Yan
Published: March 2017

The explosive growth of network traffic and its multitype on Internet have brought new and severe challenges to DDoS attack detection. To get the higher True Negative Rate (TNR), accuracy, and precision and to guarantee the robustness, stability, and universality of detection system, in this paper, we propose a DDoS attack detection method based on hybrid heterogeneous multiclassifier ensemble learning and design a heuristic detection algorithm based on Singular Value Decomposition (SVD) to construct our detection system. Experimental results show that our detection method is excellent in TNR, accuracy, and precision. Therefore, our algorithm has good detective performance for DDoS attack. Through the comparisons with Random Forest, k-Nearest Neighbor (k-NN), and Bagging comprising the component classifiers when the three algorithms are used alone by SVD and by un-SVD, it is shown that our model is superior to the state-of-the-art attack detection techniques in system generalization ability, detection stability, and overall detection performance.
Male Partners Involvement in Prevention of Mother-to-Child Transmission of HIV Services in Southern Central Ethiopia: In Case of Lemo District, Hadiya Zone
Authors: Belato Degefa Tadele , Mekiso Abera Beyamo , Begashaw Bayu
Published: March 2017

Male partners’ involvement is a vital issue to prevent human immunodeficiency virus (HIV) transmission from mother to child; because it is much expectable that women were more vulnerable and high risk group of population portion. Therefore, to save lives of mothers and their newborn from acquiring HIV, male partners should do their maximum endeavor regardless of any determinant factors as our results revealed its status in our study context and elsewhere at past time too.
A Viral Product Diffusion Model to Forecast the Market Performance of Products
Authors: Jiang Ping , Yan Xiangbin , Wang Liyan
Published: March 2017

To investigate the diffusion of products in the market, this paper proposes a viral product diffusion model using an epidemiological approach. This model presents the process of product diffusion through the dynamics of human behaviors. Based on the stability theory of Ordinary Differential Equations, we demonstrate the conditions under which a product in the market persists or dies out eventually. Next, we use Google data to validate the model. Fitting results illustrate that the viral product diffusion model not only depicts the steady growth process of products, but also describes the whole diffusion process during which the products increase at the initial stage and then gradually decrease and sometimes even exhibit multiple peaks. This shows that the viral product diffusion model can be used to forecast the developing tendency of products in the market through early behavior of these products. Moreover, our model also provides useful insights on how to design effective marketing strategies via social contagions.
Preclinical Antitumor Efficacy of BAY 1129980—a Novel Auristatin-Based Anti-C4.4A (LYPD3) Antibody–Drug Conjugate for the Treatment of Non–Small Cell Lung Cancer
Authors: Willuda Jörg , Linden Lars , Lerchen Hans-Georg , Kopitz Charlotte , Stelte-Ludwig Beatrix , Pena Carol , Lange Claudia , Golfier Sven , Kneip Christoph , Carrigan Patricia E. , Mclean Kirk , Schuhmacher Joachim , von Ahsen Oliver , Müller Jörg , Dittmer Frank , Beier Rudolf , El Sheikh Sherif , Tebbe Jan , Leder Gabriele , Apeler Heiner , Jautelat Rolf , Ziegelbauer Karl , Kreft Bertolt
Published: March 2017

C4.4A (LYPD3) has been identified as a cancer- and metastasis-associated internalizing cell surface protein that is expressed in non–small cell lung cancer (NSCLC), with particularly high prevalence in the squamous cell carcinoma (SCC) subtype. With the exception of skin keratinocytes and esophageal endothelial cells, C4.4A expression is scarce in normal tissues, presenting an opportunity to selectively treat cancers with a C4.4A-directed antibody–drug conjugate (ADC). We have generated BAY 1129980 (C4.4A-ADC), an ADC consisting of a fully human C4.4A-targeting mAb conjugated to a novel, highly potent derivative of the microtubule-disrupting cytotoxic drug auristatin via a noncleavable alkyl hydrazide linker. In vitro, C4.4A-ADC demonstrated potent antiproliferative efficacy in cell lines endogenously expressing C4.4A and inhibited proliferation of C4.4A-transfected A549 lung cancer cells showing selectivity compared with a nontargeted control ADC. In vivo, C4.4A-ADC was efficacious in human NSCLC cell line (NCI-H292 and NCI-H322) and patient-derived xenograft (PDX) models (Lu7064, Lu7126, Lu7433, and Lu7466). C4.4A expression level correlated with in vivo efficacy, the most responsive being the models with C4.4A expression in over 50% of the cells. In the NCI-H292 NSCLC model, C4.4A-ADC demonstrated equal or superior efficacy compared to cisplatin, paclitaxel, and vinorelbine. Furthermore, an additive antitumor efficacy in combination with cisplatin was observed. Finally, a repeated dosing with C4.4A-ADC was well tolerated without changing the sensitivity to the treatment. Taken together, C4.4A-ADC is a promising therapeutic candidate for the treatment of NSCLC and other cancers expressing C4.4A. A phase I study (NCT02134197) with the C4.4A-ADC BAY 1129980 is currently ongoing. Mol Cancer Ther; 16(5); 893–904. ©2017 AACR.
Synthesis and Evaluation of the Novel Prostamide, 15-Deoxy, Δ12,14-Prostamide J2, as a Selective Antitumor Therapeutic
Authors: Ladin Daniel A. , Soliman Eman , Escobedo Rene , Fitzgerald Timothy L. , Yang Li V. , Burns Colin , Van Dross Rukiyah
Published: March 2017

15-deoxy, Δ12,14-prostaglandin J2-ethanolamide, also known as 15-deoxy, Δ12,14-prostamide J2 (15d-PMJ2) is a novel product of the metabolism of arachidonoyl ethanolamide (AEA) by COX-2. 15d-PMJ2 preferentially induced cell death and apoptosis in tumorigenic A431 keratinocytes and B16F10 melanoma cells compared with nontumorigenic HaCaT keratinocytes and Melan-A melanocytes. Activation of the ER stress execution proteins, PERK and CHOP10, was evaluated to determine whether this process was involved in 15d-PMJ2 cell death. 15d-PMJ2 increased the phosphorylation of PERK and expression of CHOP10 in tumorigenic but not nontumorigenic cells. The known ER stress inhibitors, salubrinal and 4-phenylbutaric acid, significantly inhibited 15d-PMJ2–mediated apoptosis, suggesting ER stress as a primary apoptotic mediator. Furthermore, the reactive double bond present within the cyclopentenone structure of 15d-PMJ2 was identified as a required moiety for the induction of ER stress apoptosis. The effect of 15d-PMJ2 on B16F10 melanoma growth was also evaluated by dosing C57BL/6 mice with 0.5 mg/kg 15d-PMJ2. Tumors of animals treated with 15d-PMJ2 exhibited significantly reduced growth and mean weights compared with vehicle and untreated animals. TUNEL and IHC analysis of tumor tissues showed significant cell death and ER stress in tumors of 15d-PMJ2–treated compared with control group animals. Taken together, these findings suggest that the novel prostamide, 15d-PMJ2, possesses potent antitumor activity in vitro and in vivo. Mol Cancer Ther; 16(5); 838–49. ©2017 AACR.
Fatty Acid Synthesis Intermediates Represent Novel Noninvasive Biomarkers of Prostate Cancer Chemoprevention by Phenethyl Isothiocyanate
Authors: Singh Krishna B. , Singh Shivendra V.
Published: March 2017

Increased de novo synthesis of fatty acids is a distinctive feature of prostate cancer, which continues to be a leading cause of cancer-related deaths among American men. Therefore, inhibition of de novo fatty acid synthesis represents an attractive strategy for chemoprevention of prostate cancer. We have shown previously that dietary feeding of phenethyl isothiocyanate (PEITC), a phytochemical derived from edible cruciferous vegetables such as watercress, inhibits incidence and burden of poorly differentiated prostate cancer in transgenic adenocarcinoma of mouse prostate (TRAMP) model. The current study was designed to test the hypothesis of whether fatty acid intermediate(s) can serve as noninvasive biomarker(s) of prostate cancer chemoprevention by PEITC using archived plasma and tumor specimens from the TRAMP study as well as cellular models of prostate cancer. Exposure of prostate cancer cells (LNCaP and 22Rv1) to pharmacologic concentrations of PEITC resulted in downregulation of key fatty acid metabolism proteins, including acetyl-CoA carboxylase 1 (ACC1), fatty acid synthase (FASN), and carnitine palmitoyltransferase 1A (CPT1A). The mRNA expression of FASN and CPT1A as well as acetyl-CoA levels were decreased by PEITC treatment in both cell lines. PEITC administration to TRAMP mice also resulted in a significant decrease in tumor expression of FASN protein. Consistent with these findings, the levels of total free fatty acids, total phospholipids, triglyceride, and ATP were significantly lower in the plasma and/or prostate tumors of PEITC-treated TRAMP mice compared with controls. The current study is the first to implicate inhibition of fatty acid synthesis in prostate cancer chemoprevention by PEITC. Cancer Prev Res; 10(5); 279–89. ©2017 AACR.
Long-Term Effective Thalamic Deep Brain Stimulation for Neuropathic Tremor in Two Patients with Charcot-Marie-Tooth Disease
Authors: Cabañes-Martínez Lidia , Del Álamo de Pedro Marta , de Blas Beorlegui Gema , Bailly-Bailliere Ignacio Regidor
Published: March 2017

Background: It has been described that many Charcot-Marie-Tooth syndrome type 2 patients are affected by a very disabling type of tremor syndrome, the pathophysiology of which remains unclear. Deep brain stimulation (DBS) has been successfully applied to treat most types of tremors by implanting electrodes in the ventral intermediate nucleus of the thalamus (Vim). Methods: We used DBS applied to the Vim in 2 patients with severe axonal inherited polyneuropathies who developed a disabling tremor. Results: Both patients responded positively to stimulation, with a marked reduction of the tremor and with an improvement of their quality of life. Conclusion: We report 2 cases of tremor associated with a hereditary neuropathy with a good response to DBS.
Metabolic Adaptations in Pregnancy: A Review
Authors: Zeng Zhandong , Liu Fengli , Li Shixian
Published: March 2017

Background: Pregnancy is a dynamic state involving multiple adaptations that are necessary in order to ensure a continuous supply of essential metabolites to support the growth and the development of the fetus. Objectives: This review article is aimed to discuss important adaptations in metabolism that take place during non-complicated pregnancy. Materials and Methods: We searched the electronic database PubMed for pre-clinical as well as clinical controlled trials reporting the importance of metabolic adaptations during a non-complicated pregnancy. The preferred language was English and the most recent reports were selected to get an updated review. Results: It was observed clearly in the searched literature that metabolic adaptations are a crucial part of pregnancy, as they provide the mother with sufficient energy stores to meet the demands of pregnancy. These adaptions also help in preparing the mother for lactation and also help in providing proper environment for the proper growth of fetus in the womb. Moreover, multiple biomolecules including glucose, fatty acids, ketone bodies, hormones collectively contribute toward these metabolic adaptations. Conclusions: This review article concludes that metabolic adaptations are crucial for proper fetus development.
Conhecimento: custódia e acesso
Authors:   Universidade de São Paulo. Escola de Comunicações e Artes, Ferreira Sueli Mara Soares Pinto , Targino Maria das Graças ,   Universidade de São Paulo. Escola de Comunicações e Artes, Galindo Marcos ,   Universidade Federal de Pernambuco (UFPE), Sayão Luis Fernando ,   Comissão Nacional de Energia Nuclear, Sales Luana Faria ,   Instituto de Engenharia Nuclear
Published: March 2017

A mostra Conhecimento: custódia e acesso revisita o legado histórico do conhecimento da humanidade depositado em bibliotecas. Aponta, portanto, mudanças nas básicas tecnológicas das atuais bibliotecas e os diferentes contextos socioeconômicos e culturais em que se transmutam em agentes de transformação e produtoras de revoluções culturais. Dialoga, ainda, sobre os impactos das tecnologias de informação e de comunicação (TIC) em relação à sociedade contemporânea, altamente impregnada pelas inovações tecnológicas, as quais estimulam o imaginário social e individual e explora o potencial de inovação oferecido no presente, fundamentado em recursos tecnológicos de preservação e de acesso ao conhecimento. Tudo isto com vistas à reordenação do pensamento dos cidadãos no futuro próximo ou longínquo. Assim, no limiar de seus 30 anos de existência, o Sistema Integrado de Bibliotecas da Universidade de São Paulo (SIBiUSP) busca tornar transparente a ação de mais de 800 profissionais (nível superior, técnico e básico) em 44 bibliotecas alocadas em campi distribuídos em nove cidades do Estado de São Paulo. São bibliotecas que abrigam um acervo de mais de 10 mil títulos de periódicos, 100 mil teses defendidas na USP, 594 mil itens de produção USP, 264 mil de livros eletrônicos (e-books), 4,5 milhões de empréstimos a cada ano, 1,5 milhão de consultas bibliográficas anuais.
Cardiac Resynchronization Therapy Reduces Ventricular Arrhythmias in Primary but Not Secondary Prophylactic Implantable Cardioverter Defibrillator Patients
Authors: Sapp John L. , Parkash Ratika , Wells George A. , Yetisir Elizabeth , Gardner Martin J. , Healey Jeffrey S. , Thibault Bernard , Sterns Laurence D. , Birnie David , Nery Pablo B. , Sivakumaran Soori , Essebag Vidal , Dorian Paul , Tang Anthony S.L.
Published: March 2017

Background—

The RAFT (Resynchronization in Ambulatory Heart Failure Trial) demonstrated that cardiac resynchronization therapy (CRT) reduced both mortality and heart failure hospitalizations in patients with functional class II or III heart failure and widened QRS. We examined the influence of CRT on ventricular arrhythmias in patients with primary versus secondary prophylaxis defibrillator indications.

Methods and Results—

All ventricular arrhythmias among RAFT study participants were downloaded and adjudicated by 2 blinded reviewers with an overreader for disagreements and committee review for remaining discrepancies. Incidence of ventricular arrhythmias among patients randomized to CRT-D versus implantable cardioverter defibrillator (ICD) were compared within the groups of patients treated for primary prophylaxis and for secondary prophylaxis. Of 1798 enrolled patients, 1764 had data available for adjudication and were included. Of these, 1531 patients were implanted for primary prophylaxis, while 233 patients were implanted for secondary prophylaxis; 884 patients were randomized to ICD and 880 to CRT-D. During 5953.6 patient-years of follow-up, there were 11 278 appropriate ICD detections of ventricular arrhythmias. In the primary prophylaxis group, CRT-D significantly reduced incidence ventricular arrhythmias in comparison to ICD (hazard ratio, 0.86; 95% confidence interval, 0.74–0.99;
P
=0.044). This effect was not seen in the secondary prophylaxis group (hazard ratio, 1.14; 95% confidence interval, 0.82–1.58;
P
=0.45). CRT-D was not associated with significant differences in overall ventricular arrhythmia burden in either group.

Conclusions—

CRT reduced the rate of onset of new ventricular arrhythmias detected by ICDs in patients without a history of prior ventricular arrhythmias. This effect was not observed among patients who had prior ventricular arrhythmias.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00251251.
Monocyte Chemotactic Protein-1–Interleukin-6–Osteopontin Pathway of Intra-Aneurysmal Tissue Healing
Authors: Hosaka Koji , Rojas Kelley , Fazal Hanain Z. , Schneider Matheus B. , Shores Jorma , Federico Vincent , McCord Matthew , Lin Li , Hoh Brian
Published: March 2017

Background and Purpose—

We have previously demonstrated that the local delivery of monocyte chemotactic protein-1 (MCP-1) via an MCP-1–releasing poly(lactic-co-glycolic acid)–coated coil promotes intra-aneurysmal tissue healing. In this study, we demonstrate that interleukin-6 (IL-6) and osteopontin are downstream mediators in the MCP-1–mediated aneurysm-healing pathway.

Methods—

Murine carotid aneurysms were created in C57BL/6 mice. Drug-releasing coils (MCP-1, IL-6, and osteopontin) and control poly(lactic-co-glycolic acid) coils were created and then implanted into the aneurysms to evaluate their intra-aneurismal–healing capacity. To investigate the downstream mediators for aneurysm healing, blocking antibodies for IL-6 receptor and osteopontin were given to the mice implanted with the MCP-1–releasing coils. A histological analysis of both murine and human aneurysms was utilized to cross-validate the data.

Results—

We observed increased expression of IL-6 in MCP-1-coil–treated aneurysms and not in control-poly(lactic-co-glycolic acid)-only–treated aneurysms. MCP-1–mediated intra-aneurysmal healing is inhibited in mice given blocking antibody to IL-6 receptor. MCP-1–mediated intra-aneurysmal healing is also inhibited by blocking antibody to osteopontin. The role of IL-6 in intra-aneurysmal healing is in recruiting of endothelial cells and fibroblasts. Local delivery of osteopontin to murine carotid aneurysms via osteopontin-releasing coil significantly promotes intra-aneurysmal healing, but IL-6–releasing coil does not, suggesting that IL-6 cannot promote aneurysm healing independent of MCP-1. In the MCP-1–mediated aneurysm healing, osteopontin expression is dependent on IL-6; inhibition of IL-6 receptor significantly inhibits osteopontin expression in MCP-1–mediated aneurysm healing.

Conclusions—

Our findings suggest that IL-6 and osteopontin are key downstream mediators of MCP-1–mediated intra-aneurysmal healing.
Regional Comparison of Multiphase Computed Tomographic Angiography and Computed Tomographic Perfusion for Prediction of Tissue Fate in Ischemic Stroke
Authors: d’Esterre Christopher D. , Trivedi Anurag , Pordeli Pooneh , Boesen Mari , Patil Shivanand , Hwan Ahn Seong , Najm Mohamed , Fainardi Enrico , Shankar Jai Jai Shiva , Rubiera Marta , Almekhlafi Mohammed A. , Mandzia Jennifer , Khaw Alexander V. , Barber Philip , Coutts Shelagh , Hill Michael D. , Demchuk Andrew M. , Sajobi Tolulope , Forkert Nils D. , Goyal Mayank , Lee Ting-Yim , Menon Bijoy K.
Published: March 2017

Background and Purpose—

Within different brain regions, we determine the comparative value of multiphase computed tomographic angiography (mCTA) and computed tomographic perfusion (CTP) in predicting follow-up infarction.

Methods—

Patients with M1-middle cerebral artery occlusions were prospectively included in this multicenter study. Regional analysis was performed for each patient within Alberta Stroke Program Early CT Score regions M2 to M6. Regional pial vessel filling was assessed on mCTA in 3 ways: (1) Washout of contrast within pial vessels; (2) Extent of maximal pial vessel enhancement compared with contralateral hemisphere; (3) Delay in maximal pial vessel enhancement compared with contralateral hemisphere. Cerebral blood flow, cerebral blood volume, and Tmax data were extracted within these Alberta Stroke Program Early CT Score regions. Twenty-four- to 36-hour magnetic resonance imaging/CT was assessed for infarct in each Alberta Stroke Program Early CT Score region (defined as >20% infarction within that region). Mixed effects logistic regression models were used to compare mCTA and CTP parameters when predicting brain infarction. Area under the receiver operating characteristics was used to assess discriminative value of statistical models.

Results—

Seventy-seven patients were included. mCTA parameter washout and CTP parameter Tmax were significantly associated with follow-up infarction in all models (
P
<0.05). The area under the receiver operating characteristic for mCTA models ranged from 92% to 94% and was not different compared with all CTP models (
P
>0.05). Mean Tmax and cerebral blood volume values were significantly different between each washout score (
P
<0.01) and each delay score category (
P
<0.01). Mean Tmax, cerebral blood flow, and cerebral blood volume values were significantly different between each extent score category (
P
<0.05).

Conclusions—

Similar to CTP, multiphase CTA can be used to predict tissue fate regionally in acute ischemic stroke patients.
Taking Action against Fishing Vessels without Nationality: Have Recent International Developments Clarified the Law?
Authors: Scanlon Zoe
Published: March 2017

Due to the ambiguity of international law in this area, taking action against vessels without nationality on the high seas has been inherently problematic. In recent years, however, a number of legal developments have emerged in the international fisheries sphere, designed to address this uncertainty. This article considers the ambiguity in this area, describes recent legal developments and contemplates their impact on the law, including their potential to contribute to the development of a new customary norm, or represent evidence of an international legal and political consensus on existing law. It considers the likelihood that these recent developments, whatever their precise legal effect, will facilitate the international community’s efforts in combatting illegal, unreported and unregulated fishing into the future.
The Role of the United Nations in the Formation of Customary International Law in the Field of Human Rights
Authors: Droubi Sufyan
Published: March 2017

The present work addresses the role of un in the formation of customary international law from a constructivist perspective. It dialogues with the International Law Commission and, in contrast with the latter, it argues that the importance of the un is a matter to be defined empirically. Its organs are capable of acting as norm entrepreneurs, articulating and promoting new norms. They are capable of affecting social processes in order to create pressure on the states that resist emergent norms. Thus, instead of a mere agent of states the un is capable of deeply influencing them both in behavioural and attitudinal terms. Furthermore, the un promote the formalization and institutionalization of new norms, elucidating their scope, application, and embedding them in consistently coherent amalgamation of norms and practices. Hence, it is capable of fostering the processes that lead to the crystallization of norms as customary international law.
Practical Necessity and the Fulfilment of the Plan of Nature in Kant’s Idea for a Universal History
Authors: James David
Published: March 2017

I explore the role of practical necessity in Kant’s essay Idea for a Universal History with a Cosmopolitan Aim. This form of necessity arises on the basis of social and interstate antagonism and Kant appeals to it with the aim of avoiding the introduction of a standpoint that is external to the agents whose attitudes and actions are being described. In connection with the role that Kant accords to practical necessity in the establishment of the legal and political conditions required to fulfil the ‘plan of nature’ in the course of history, I argue that in this essay he fails to identify a mechanism that would explain a fundamental moral change in that which motivates human beings once these conditions have been established. This in turn invites questions concerning the kind of universal history that Kant proposes. In particular, I argue that the choice of historical material that it demands could, in certain circumstances, be regarded as counterpurposive in relation to the aim of nature of which Kant speaks in the same essay.
Rhetoric and Rivalry
Authors: Teilanyo Diri I.
Published: March 2017

Politics almost always entails opposition and rivalry as individuals and groups compete for power and influence. This essay juxtaposes the use of rhetoric among political rivals in Chinua Achebe’s Arrow of God with the use of such language among present-day Nigerian politicians. Parallels are drawn between the utterances of such characters as Ezeulu, Nwaka, and Ezidemili in Arrow of God and those of Nigerian political personalities like Olusegun Obasanjo, Goodluck Jonathan, Ibrahim Babangida, and Atiku Abubakar (the statements of the Nigerian politicians having been gathered from the mass media). Rhetorical strategies such as wit, repartee, innuendo, cynical/wry humour, and outright abuse/imprecations are identified as shared in the two worlds. It is argued that such language of rivalry is common in all political settings, ancient or modern. It is also suggested that literary works such as Arrow of God constitute a source of both political wit and wisdom for politicians to draw on.
A Switch of Class?
Authors: Adegbulu Femi
Published: March 2017

So much has been written about Nigeria–Ghana relations. However, very little attempt has been made to interrogate and historicize their competing status as independent states in the same sub-region over the decades. The two states have common historical experiences in terms of pre-colonial interactions, colonial rule, military dictatorship, and modern institutions. But, shortly after independence, their hitherto smooth relationship became competitive and at times, mutually antagonistic. It is this competitiveness that this essay investigates. In addition, it examines Nigeria’s claim to be the giant of Africa (and as a world player) while other, neighbouring West African states, including Ghana, are mere Lilliputians. The essay recalls the pitiable experience of Ghanaian nationals taking economic refuge in Nigeria in the 1980s—clutching at any kinds of menial jobs they could lay their hands on. In this connection, the essay is particularly fascinated by the obvious change of tide, which seems to be moving in favour of Ghana. With all positive indices of development being present in Ghana while, conversely, Nigeria suffers from the lack of these, the essay wonders whether Nigeria’s claim to be a giant can still hold water. It concludes with a rather shocking revelation which suggests the reversal of positions between the two countries.
Writing ‘Parrhesia’, Narrating ‘the Other Rwandan Genocide’
Authors: Tembo Nick Mdika
Published: March 2017

At the end of the 1994 Rwandan genocide, close to a million Tutsis and moderate Hutus had been murdered, and over 1.5 million people were either internally displaced or had fled over the borders into neighbouring countries and beyond for fear of reprisals from the advancing Rwandan Patriotic Front (RPF). This article places Marie Béatrice Umutesi’s Surviving the Slaughter (2004) and Pierre-Claver Ndacyayisenga’s Dying to Live (2012) within the context of post-1994 Rwandan testimonial literature that writes what is feared to be “the other Rwandan genocide,” particularly against those who fled to eastern Zaïre (now the Democratic Republic of Congo). In the two narratives, I argue, Umutesi and Ndacyayisenga destabilise and deconstruct the claim of genocide to create a literature that captures the anxieties of genocide memories in Rwanda. Specifically, Umutesi and Ndacyayisenga deploy a rhetorical narrative form that employs cynicism, bitter humour and a harsh tone to suggest that the suffering of Rwandans must not be seen, or even told, from a single perspective, and that only a balanced engagement with extant issues would lead to genuine reconciliation in Rwanda. To illustrate the ideological purpose at work in the two texts, I reference Michel Foucault’s parrhesia as a framework for understanding how the authors contest genocide memories in Rwanda.
Towards a Transsystemic Study of the Ghana Legal System
Authors: Adusei Poku
Published: March 2017

This article provides comprehensive insights into the study of the Ghana legal system as an academic discipline in the law faculties in Ghana. It urges the view that the study of the Ghana legal system, as an academic discipline, should be transsystemic. Transsystemic pedagogy consists in the introduction of ideas, structures and principles which may be drawn from different legal traditions such as civil law, common law, religion-based law, African law and socialist law traditions to influence the study of law. Transsystemia involves teaching law ‘across,’ ‘through,’ and ‘beyond’ disciplinary fixations associated with a particular legal system. It is a mode of scholarship that defies biased allegiance to one legal tradition in order to foster cross-cultural dialogue among legal traditions. It involves a study of law that re-directs focus from one concerned with ‘pure’ legal system to a discourse that is grounded on multiple legal traditions.