bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent cohort effects in suicide in Scotland: a legacy of the 1980s?
Authors: Parkinson Jane , Minton Jon , Lewsey James , Bouttell Janet , McCartney Gerry
Published: July 2016

Background

Mortality rates are higher in Scotland relative to England and Wales, even after accounting for deprivation. This ‘excess’ mortality is partly due to higher mortality from alcohol-related and drug-related deaths, violence and suicide (particularly in young adults). This study investigated whether cohort effects from exposure to neoliberal politics from the 1980s might explain the recent trends in suicide in Scotland.

Methods

We analysed suicide deaths data from 1974 to 2013 by sex and deprivation using shaded contour plots and intrinsic estimator regression modelling to identify and quantify relative age, period and cohort effects.

Results

Suicide was most common in young adults (aged around 25–40 years) living in deprived areas, with a younger peak in men. The peak age for suicide fell around 1990, especially for men for whom it dropped quickly from around 50 to 30 years. There was evidence of an increased risk of suicide for the cohort born between 1960 and 1980, especially among men living in the most deprived areas (of around 30%). The cohort at highest risk occurred earlier in the most deprived areas, 1965–1969 compared with 1970–1974.

Conclusions

The risk of suicide increased in Scotland for those born between 1960 and 1980, especially for men living in the most deprived areas, which resulted in a rise in age-standardised rates for suicide among young adults during the 1990s. This is consistent with the hypothesis that exposure to neoliberal politics created a delayed negative health impact.
Faster heart rate and muscular oxygen uptake kinetics in type 2 diabetes patients following endurance training
Authors: Koschate Jessica , Drescher Uwe , Brinkmann Christian , Baum Klaus , Schiffer Thorsten , Latsch Joachim , Brixius Klara , Hoffmann Uwe
Published: July 2016

Cardiorespiratory kinetics were analyzed in type 2 diabetes patients before and after a 12-week endurance exercise-training intervention. It was hypothesized that muscular oxygen uptake and heart rate (HR) kinetics would be faster after the training intervention and that this would be detectable using a standardized work rate protocol with pseudo-random binary sequences. The cardiorespiratory kinetics of 13 male sedentary, middle-aged, overweight type 2 diabetes patients (age, 60 ± 8 years; body mass index, 33 ± 4 kg·m−2) were tested before and after the 12-week exercise intervention. Subjects performed endurance training 3 times a week on nonconsecutive days. Pseudo-random binary sequences exercise protocols in combination with time series analysis were used to estimate kinetics. Greater maxima in cross-correlation functions (CCFmax) represent faster kinetics of the respective parameter. CCFmax of muscular oxygen uptake (pre-training: 0.31 ± 0.03; post-training: 0.37 ± 0.1, P = 0.024) and CCFmax of HR (pre-training: 0.25 ± 0.04; post-training: 0.29 ± 0.06, P = 0.007) as well as peak oxygen uptake (pre-training: 24.4 ± 4.7 mL·kg−1·min−1; post-training: 29.3 ± 6.5 mL·kg−1·min−1, P = 0.004) increased significantly over the course of the exercise intervention. In conclusion, kinetic responses to changing work rates in the moderate-intensity range are similar to metabolic demands occurring in everyday habitual activities. Moderate endurance training accelerated the kinetic responses of HR and muscular oxygen uptake. Furthermore, the applicability of the used method to detect these accelerations was demonstrated.
Mapping the accumulation of woody biomass in Mediterranean beech forests by the combination of BIOME-BGC and ancillary data
Authors: Lombardi F. , Chiesi M. , Maselli F. , Di Benedetto S. , Marchetti M. , Chirici G. , Tognetti R.
Published: July 2016

A modelling strategy is proposed to obtain spatially explicit estimates of net carbon accumulation in Italian beech forests. This approach is based on the use of a biogeochemical model, BIOME-BGC, which is capable of simulating all main processes of ecosystems in quasi-equilibrium conditions. The model predictions are then corrected for actual forest biomass (growing stock volume) and stand age. The method is applied to predict the current annual increment (CAI) of 30 beech forest stands in Molise, Central Italy, which have been sampled during several measurement campaigns. A preliminary test is conducted to assess the model’s ability to reproduce the interannual production variations of these stands. Trials are then carried out driving the modelling strategy with both growing stock measurements collected in the field and a recently produced growing stock map. The final CAI estimates are validated through comparison with conventionally collected dendrochronological measurements. The results obtained indicate that the modelling approach is capable of reproducing interannual variations of net primary production and estimating the ground CAIs with an acceptable accuracy and when driven by the mapped growing stock. Additionally, the CAI estimates are not affected by the silvicultural system and development stage of the observed stands.
Berberine Preconditioning Protects Neurons Against Ischemia via Sphingosine-1-Phosphate and Hypoxia-Inducible Factor-1α
Authors: Zhang Qichun , Bian Huimin , Guo Liwei , Zhu Huaxu
Published: July 2016

Berberine exerts neuroprotective and modulates hypoxia inducible factor-1-alpha (HIF-1[Formula: see text]. Based on the role of HIF-1[Formula: see text] in hypoxia preconditioning and association between HIF-1[Formula: see text] and sphingosine-1-phosphate (S1P), we hypothesized that berberine preconditioning (BP) would ameliorate the cerebral injury induced by ischemia through activating the system of HIF-1[Formula: see text] and S1P. Adult male rats with middle cerebral artery occlusion (MCAO) and rat primary cortical neurons treated with oxygen and glucose deprivation (OGD) with BP at 24[Formula: see text]h (40[Formula: see text]mg/kg) and 2[Formula: see text]h (10[Formula: see text][Formula: see text]mol/L), respectively, were used to determine the neuroprotective effects. The HIF-1[Formula: see text] accumulation, and S1P metabolism were assayed in the berberine-preconditioned neurons, and the HIF-1[Formula: see text]-mediated transcriptional modulation of sphingosine kinases (Sphk) 1 and 2 was analyzed using chromatin immunoprecipitation and real-time polymerase chain reaction. BP significantly prevented cerebral ischemic injury in the MCAO rats at 24[Formula: see text]h and 72[Formula: see text]h following ischemia/reperfusion. In OGD-treated neurons, BP enhanced HIF-1[Formula: see text] accumulation with activation of PI3K/Akt, and induced S1P production by activating Sphk2 via the promotion of HIF-1[Formula: see text]-mediated Sphk2 transcription. In conclusion, BP activated endogenous neuroprotective mechanisms associated with the S1P/HIF-1 pathway and helped protect neuronal cells against hypoxia/ischemia.
Balanced finite presentations of the trivial group
Authors: Lishak Boris
Published: July 2016

We construct a sequence of balanced finite presentations of the trivial group with two generators and two relators with the following property: The minimal number of relations required to demonstrate that a generator represents the trivial element grows faster than the tower of exponentials of any fixed height of the length of the finite presentation.
Executing Dynamic Data-Graph Computations Deterministically Using Chromatic Scheduling
Authors: Kaler Tim , Hasenplaugh William , Schardl Tao B. , Leiserson Charles E.
Published: July 2016

A data-graph computation—popularized by such programming systems as Galois, Pregel, GraphLab, PowerGraph, and GraphChi—is an algorithm that performs local updates on the vertices of a graph. During each round of a data-graph computation, an update function atomically modifies the data associated with a vertex as a function of the vertex’s prior data and that of adjacent vertices. A dynamic data-graph computation updates only an active subset of the vertices during a round, and those updates determine the set of active vertices for the next round.

This article introduces P
rism
, a chromatic-scheduling algorithm for executing dynamic data-graph computations. P
rism
uses a vertex coloring of the graph to coordinate updates performed in a round, precluding the need for mutual-exclusion locks or other nondeterministic data synchronization. A multibag data structure is used by P
rism
to maintain a dynamic set of active vertices as an unordered set partitioned by color. We analyze P
rism
using work-span analysis. Let
G
= (
V
,
E
) be a degree-Δ graph colored with χ colors, and suppose that
Q
⊆
V
is the set of active vertices in a round. Define
size
(
Q
)= |
Q
| + ∑

v
∈
Q

deg(
v
), which is proportional to the space required to store the vertices of
Q
using a sparse-graph layout. We show that a
P
-processor execution of P
rism
performs updates in
Q
using
O
(χ (lg (
Q/χ
) + lg Δ ) + lg
P
span and Θ(
size
(
Q
) +
P
) work.

These theoretical guarantees are matched by good empirical performance. To isolate the effect of the scheduling algorithm on performance, we modified GraphLab to incorporate P
rism
and studied seven application benchmarks on a 12-core multicore machine. P
rism
executes the benchmarks 1.2 to 2.1 times faster than GraphLab’s nondeterministic lock-based scheduler while providing deterministic behavior.

This article also presents P
rism
-R, a variation of P
rism
that executes dynamic data-graph computations deterministically even when updates modify global variables with associative operations. P
rism
-R satisfies the same theoretical bounds as P
rism
, but its implementation is more involved, incorporating a multivector data structure to maintain a deterministically ordered set of vertices partitioned by color. Despite its additional complexity, P
rism
-R is only marginally slower than P
rism
. On the seven application benchmarks studied, P
rism
-R incurs a 7% geometric mean overhead relative to P
rism
.
The Association between Different Levels of Alcohol Use and Gait under Single and Dual Task in Community-Dwelling Older Persons Aged 65 to 70 Years
Authors: Seematter-Bagnoud Laurence , Büla Christophe , Santos-Eggimann Brigitte
Published: July 2016

Objectives. This study aimed to describe the cross-sectional and longitudinal association between alcohol intake and gait parameters in older persons.Methods. Community-dwelling persons aged 65–70 years (N=807). Information on health, functional status, and alcohol use was self-reported at baseline and at 3-year follow-up, whereas gait speed and stride-to-stride variability were measured while walking only (single task) and under dual tasking (counting backwards).Results. Compared to light-to-moderate drinking, heavy drinking was associated with slower gait speed in single task (adj. coeff.: −.040, 95% CI: −.0.78 to −.002,p=.035). No significant association was observed between heavy drinking and gait speed variability. Nondrinkers walked significantly slower than light-to-moderate drinkers in dual task and had significantly higher gait speed variability in both single and dual task, but these associations disappeared after adjustment for comorbidity. At follow-up, 35.2% and 34.1% of the participants walked significantly slower in single and dual task, respectively. This proportion varied a little across drinking categories.Conclusion. At baseline, heavy alcohol consumption was significantly associated with slower gait speed in single task. Selective survival of the fittest heavy drinkers probably explains why this association faded in longitudinal analyses. The trend of poorer gait performance in nondrinkers disappeared after adjustment for comorbidity, suggesting confounding by a worse health status.
Enhanced Absorption Study of Ginsenoside Compound K (20‐O‐β‐(D‐Glucopyranosyl)‐20(S)‐protopanaxadiol) after Oral Administration of Fermented Red Ginseng Extract (HYFRG™) in Healthy Korean Volunteers and Rats
Authors: Choi Il-Dong , Ryu Ju-Hee , Lee Dong-Eun , Lee Myoung-Hee , Shim Jae-Joong , Ahn Young-Tae , Sim Jae-Hun , Huh Chul-Sung , Shim Wang-Seob , Yim Sung-Vin , Chung Eun-Kyoung , Lee Kyung-Tae
Published: July 2016

To evaluate the pharmacokinetics of compound K after oral administration of HYFRG and RG in humans, an open‐label, randomized, single‐dose, fasting, and one‐period pharmacokinetic study was conducted. After oral administration of a single 3 g dose of HYFRG and RG to 24 healthy Korean males, the mean (±SD) of AUC0–t and Cmax of compound K from HYFRG were 1466.83 ± 295.89 ng·h/mL and 254.45 ± 51.20 ng/mL, being 115.2‐ and 80‐fold higher than those for RG (12.73 ± 7.83 ng·h/mL and 3.18 ± 1.70 ng/mL), respectively; in case of Sprague Dawley rats the mean (±SD) of AUC0–t and Cmax of compound K from HYFRG was 58.03 ± 32.53 ng·h/mL and 15.19 ± 10.69 ng/mL, being 6.3‐ and 6.0‐fold higher than those from RG (9.21 ± 7.52 ng·h/mL and 2.55 ± 0.99 ng/mL), respectively. Tmax of compound K in humans and rats was 2.54 ± 0.92 and 3.33 ± 0.50 h for HYFRG and 9.11 ± 1.45 and 6.75 ± 3.97 hours for RG, respectively. In conclusion, the administration of HYFRG resulted in a higher and faster absorption of compound K in both humans and rats compared to RG.
High-Density Lipoprotein Binds toMycobacterium aviumand Affects the Infection of THP-1 Macrophages
Authors: Ichimura Naoya , Sato Megumi , Yoshimoto Akira , Yano Kouji , Ohkawa Ryunosuke , Kasama Takeshi , Tozuka Minoru
Published: July 2016

High-density lipoprotein (HDL) is involved in innate immunity toward various infectious diseases. Concerning bacteria, HDL is known to bind to lipopolysaccharide (LPS) and to neutralize its physiological activity. On the other hand, cholesterol is known to play an important role in mycobacterial entry into host cells and in survival in the intracellular environment. However, the pathogenicity ofMycobacterium avium(M. avium) infection, which tends to increase worldwide, remains poorly studied. Here we report that HDL indicated a stronger interaction withM. aviumthan that with other Gram-negative bacteria containing abundant LPS. A binding of apolipoprotein (apo) A-I, the main protein component of HDL, with a specific lipid ofM. aviummight participate in this interaction. HDL did not have a direct bactericidal activity towardM. aviumbut attenuated the engulfment ofM. aviumby THP-1 macrophages. HDL also did not affect bacterial killing after ingestion of liveM. aviumby THP-1 macrophage. Furthermore, HDL strongly promoted the formation of lipid droplets inM. avium-infected THP-1 macrophages. These observations provide new insights into the relationship betweenM. aviuminfection and host lipoproteins, especially HDL. Thus, HDL may helpM. aviumto escape from host innate immunity.
Bone and Joint Infections due toHaemophilus parainfluenzae: Case Report and Review of the Literature
Authors: O’Neil Conar R. , Wilson Evan , Missaghi Bayan
Published: July 2016

Haemophilus parainfluenzaeis a normal inhabitant of the human respiratory tract. However it is an increasingly recognized pathogen in invasive infections, particularly in the immunocompromised host and where there is disruption of the normal skin or mucosal barriers. We present a case of a 56-year-old female with a history of asplenia who developedH. parainfluenzaeseptic arthritis of the hip following an intra-articular steroid injection. We also summarize previously reported cases of bone and joint infections caused byH. parainfluenzae.
Shape Preserving Interpolation UsingC2Rational Cubic Spline
Authors: Abdul Karim Samsul Ariffin , Voon Pang Kong
Published: July 2016

This paper discusses the construction of newC2rational cubic spline interpolant with cubic numerator and quadratic denominator. The idea has been extended to shape preserving interpolation for positive data using the constructed rational cubic spline interpolation. The rational cubic spline has three parametersαi,βi, andγi. The sufficient conditions for the positivity are derived on one parameterγiwhile the other two parametersαiandβiare free parameters that can be used to change the final shape of the resulting interpolating curves. This will enable the user to produce many varieties of the positive interpolating curves. Cubic spline interpolation withC2continuity is not able to preserve the shape of the positive data. Notably our scheme is easy to use and does not require knots insertion andC2continuity can be achieved by solving tridiagonal systems of linear equations for the unknown first derivativesdi,i=1,…,n-1. Comparisons with existing schemes also have been done in detail. From all presented numerical results the newC2rational cubic spline gives very smooth interpolating curves compared to some established rational cubic schemes. An error analysis when the function to be interpolated isft∈C3t0,tnis also investigated in detail.
Determination of Critical Load in a Nonuniform Circular Steel Column under the Eccentric Axial Load
Authors: Kotšmíd Stanislav , Kuo Chang-Hung , Beňo Pavel
Published: July 2016

The purpose of this paper is to determine a critical load for a nonuniform circular steel tube under eccentrically axial load. The circular tube has variable cross section at flattened ends with existing holes used for connection between members. Three different cases of eccentricities are studied with the drilled holes either on the same side or on the opposite side of column axis. The critical load is calculated from the differential equation of deflection curve which is solved by the power series and Runge-Kutta method. In addition, the loading tests were performed on a total of 180 specimens with different diameters, slenderness, and connection. The calculated results are compared and shown in a good agreement with those obtained from the experimental results. The results also show that the critical load decreases rapidly even at a small value of eccentricity and thus may have a significant effect on the load-carrying capacity.
Modeling and Nonlinear Response of the Cam-Follower Oblique-Impact System
Authors: Yang Yong-Feng , Lu Yu , Jiang Ting-Dong , Lu Na
Published: July 2016

In order to quickly and accurately analyze the complex behavior of cam-follower oblique-impact system, a mathematical model which can describe separation, impact, and contact was established in this paper. The transient impact hypothesis was extended, and the oblique collision model was established by considering the tangential slip. Moreau time-stepping method was employed to solve the linear complementarity problem which transformed by the oblique-impact equations. The simulation results show that the cam and follower kept permanent contact when the cam rotational speed was low. With the increase of the cam rotational speed, the cam and follower would be separated and then impact under the gravity action. The system performance shows very complex nonlinear characteristics.
Punicalagin Induces Serum Low‐Density Lipoprotein Influx to Macrophages
Authors: Atrahimovich Dana , Khatib Soliman , Sela Shifra , Vaya Jacob , Samson Abraham O.
Published: July 2016

High levels of circulating low‐density lipoprotein (LDL) are a primary initiating event in the development of atherosclerosis. Recently, the antiatherogenic effect of polyphenols has been shown to be exerted via a mechanism unrelated to their antioxidant capacity and to stem from their interaction with specific intracellular or plasma proteins. In this study, we investigated the interaction of the main polyphenol in pomegranate, punicalagin, with apolipoprotein B‐100 (ApoB100) that surrounds LDL. Punicalagin bound to ApoB100 at low concentrations (0.25–4 μM). Upon binding, it induced LDL influx to macrophages in a concentration‐dependent manner, up to 2.5‐fold. In contrast, another polyphenol which binds to ApoB100, glabridin, did not affect LDL influx. We further showed that LDL influx occurs specifically through the LDL receptor, with LDL then accumulating in the cell cytoplasm. Taken together with the findings of Aviram et al., 2000, that pomegranate juice and punicalagin induce plasma LDL removal and inhibit macrophage cholesterol synthesis and accumulation, our results suggest that, upon binding, punicalagin stimulates LDL influx to macrophages, thus reducing circulating cholesterol levels.
Emergency Communication and Quick Seismic Damage Investigation Based on Smartphone
Authors: Han Ruicong , Zhao Xuefeng , Yu Yan , Guan Quanhua , Peng Deli , Li Mingchu , Ou Jinping
Published: July 2016

The communications in the quake-hit area are always cut off from the outside after the earthquake, and the traditional seismic field investigation method calls for immense time to accomplish house-to-house investigation, which goes against timeliness of the emergency rescue. In this paper, an emergency communication and quick seismic damage investigation method based on smartphone is proposed. Towards this, an application, E-Explorer, on iOS platform is initially developed. First, in the emergency communication module, the communication is available by using the Multipeer Connectivity Framework technology even without external network. A series of validation experiments are simulated without external network, and the results prove convincing. This module enhances the possibility of communication and increases the chances for rescue. Second, in the damage investigation module, E-Explorer integrates the functions of questionnaire and picture collection for damage phenomenon recording and image acquisition, following an intensity evaluation method according to seismic index. Last, a website, which provides guidance for rescue workers and collects damage information for quick intensity evaluation, is being built.
Surgical Management of Massive Pericardial Effusion and Predictors for Development of Constrictive Pericarditis in a Resource Limited Setting
Authors: Kesieme Emeka B. , Okokhere Peter O. , Iruolagbe Christopher Ojemiega , Odike Angela , Owobu Clifford , Akhigbe Theophilus
Published: July 2016

Background. The diagnosis and treatment of massive pericardial effusion and cardiac tamponade have evolved over the years with a tendency towards a more comprehensive diagnostic workup and less traumatic intervention.Method. We reviewed and analysed the data of 32 consecutive patients who underwent surgery on account of massive pericardial effusion and cardiac tamponade in a semiurban university hospital in Nigeria from February 2010 to February 2016.Results. The majority of patients (34.4%) were between 31 and 40 years. Fourteen patients (43.8%) presented with clinical and echocardiographic feature of cardiac tamponade. The majority of patients (59.4%) presented with haemorrhagic pericardial effusion and the average volume of fluid drained intraoperatively was 846 mL  ± 67 mL. Pericardium was thickened in 50% of cases. Subxiphoid pericardiostomy was performed under local anaesthesia in 28 cases. No postoperative recurrence was observed; however 5 patients developed features of constrictive pericarditis. The relationship between pericardial thickness and development of pericardial constriction was statistically significant (p=0.004).Conclusion. Subxiphoid pericardiostomy is a very effective way of treating massive pericardial effusion. Removing tube after adequate drainage (50 mL/day) and treatment of primary pathology are key to preventing recurrence. There is also a need to follow up patients to detect pericardial constriction especially those with thickened pericardium.
Clinical Utility of Bronchoalveolar Lavage Pepsin in Diagnosis of Gastroesophageal Reflux among Wheezy Infants
Authors: Abdallah Ahmed Fathi , El-Desoky Tarek , Fathi Khalid , Elkashef Wagdy Fawzi , Zaki Ahmed
Published: July 2016

Background. There is no gold standard test for diagnosis of gastroesophageal reflux disease (GERD) associated infantile wheezing.Objectives. To evaluate the value of bronchoalveolar lavage (BAL) pepsin assay in diagnosis of GERD in wheezy infants.Methods. Fifty-two wheezy infants were evaluated for GERD using esophageal combined impedance-pH (MII-pH) monitoring, esophagogastroduodenoscopy with esophageal biopsies, and BAL pepsin. Tracheobronchial aspirates from 10 healthy infants planned for surgery without history of respiratory problems were examined for pepsin.Results. Wheezy infants with silent reflux and wheezy infants with typical GERD symptoms but normal MII-pH had significantly higher BAL pepsin compared to healthy control (45.3 ± 8.6 and 42.8 ± 8 versus 29 ± 2.6,P<0.0001andP=0.011, resp.). BAL pepsin had sensitivity (61.7%, 72 %, and 70%) and specificity (55.5%, 52.9%, and 53%) to diagnose GERD associated infantile wheeze compared to abnormal MII-pH, reflux esophagitis, and lipid laden macrophage index, respectively.Conclusion. A stepwise approach for assessment of GERD in wheezy infants is advised. In those with silent reflux, a trial of antireflux therapy is warranted with no need for further pepsin assay. But when combined MII-pH is negative despite the presence of typical GERD symptoms, pepsin assay will be needed to rule out GERD related aspiration.
West Nile Virus Encephalitis in a Patient with Neuroendocrine Carcinoma
Authors: Deldar Romina , Thomas Derek , Storniolo Anna Maria
Published: July 2016

Importance. Oftentimes, when patients with metastatic cancer present with acute encephalopathy, it is suspected to be secondary to their underlying malignancy. However, there are multiple causes of delirium such as central nervous system (CNS) infections, electrolyte abnormalities, and drug adverse reactions. Because West Nile Virus (WNV) neuroinvasive disease has a high mortality rate in immunosuppressed patients, a high index of suspicion is required in patients who present with fever, altered mental status, and other neurological symptoms.Observations. Our case report details a single patient with brain metastases who presented with unexplained fever, encephalopathy, and new-onset tremors. Initially, it was assumed that his symptoms were due to his underlying malignancy or seizures. However, because his unexplained fevers persisted, lumbar puncture was pursued. Cerebrospinal fluid analysis included WNV polymerase chain reaction and serologies were ordered which eventually led to diagnosis of WNV encephalitis.Conclusions and Relevance. Patients with metastatic cancer who present with encephalopathy are often evaluated with assumption that malignancy is the underlying etiology. This can lead to delays in diagnosis and possible mistreatment. Our case highlights the importance of maintaining a broad differential diagnosis and an important diagnostic consideration of WNV encephalitis in patients with cancer.
Bifurcation Analysis of Gene Propagation Model Governed by Reaction-Diffusion Equations
Authors: Lu Guichen
Published: July 2016

We present a theoretical analysis of the attractor bifurcation for gene propagation model governed by reaction-diffusion equations. We investigate the dynamical transition problems of the model under the homogeneous boundary conditions. By using the dynamical transition theory, we give a complete characterization of the bifurcated objects in terms of the biological parameters of the problem.
Targeting KIR Blockade in Multiple Myeloma: Trouble in Checkpoint Paradise?
Authors: Felices Martin , Miller Jeffrey S.
Published: July 2016

Findings within the current issue indicate that treatment with IPH2101 when used as a monotherapy in smoldering multiple myeloma, meant to enhance natural killer (NK) cell function through inhibitory KIR blockade, results in a surprising reduction of NK-cell function mediated through monocyte trogocytosis. The significance of these findings is discussed. Clin Cancer Res; 22(21); 5161–3. ©2016 AACR.

See related article by Carlsten et al., p. 5211
Molecular Mechanisms of Resistance to First- and Second-Generation ALK Inhibitors inALK-Rearranged Lung Cancer
Authors: Gainor Justin F. , Dardaei Leila , Yoda Satoshi , Friboulet Luc , Leshchiner Ignaty , Katayama Ryohei , Dagogo-Jack Ibiayi , Gadgeel Shirish , Schultz Katherine , Singh Manrose , Chin Emily , Parks Melissa , Lee Dana , DiCecca Richard H. , Lockerman Elizabeth , Huynh Tiffany , Logan Jennifer , Ritterhouse Lauren L. , Le Long P. , Muniappan Ashok , Digumarthy Subba , Channick Colleen , Keyes Colleen , Getz Gad , Dias-Santagata Dora , Heist Rebecca S. , Lennerz Jochen , Sequist Lecia V. , Benes Cyril H. , Iafrate A. John , Mino-Kenudson Mari , Engelman Jeffrey A. , Shaw Alice T.
Published: July 2016

Advanced, anaplastic lymphoma kinase (ALK)–positive lung cancer is currently treated with the first-generation ALK inhibitor crizotinib followed by more potent, second-generation ALK inhibitors (e.g., ceritinib and alectinib) upon progression. Second-generation inhibitors are generally effective even in the absence of crizotinib-resistant ALK mutations, likely reflecting incomplete inhibition of ALK by crizotinib in many cases. Herein, we analyzed 103 repeat biopsies from ALK-positive patients progressing on various ALK inhibitors. We find that each ALK inhibitor is associated with a distinct spectrum of ALK resistance mutations and that the frequency of one mutation, ALKG1202R, increases significantly after treatment with second-generation agents. To investigate strategies to overcome resistance to second-generation ALK inhibitors, we examine the activity of the third-generation ALK inhibitor lorlatinib in a series of ceritinib-resistant, patient-derived cell lines, and observe that the presence of ALK resistance mutations is highly predictive for sensitivity to lorlatinib, whereas those cell lines without ALK mutations are resistant.

Significance: Secondary ALK mutations are a common resistance mechanism to second-generation ALK inhibitors and predict for sensitivity to the third-generation ALK inhibitor lorlatinib. These findings highlight the importance of repeat biopsies and genotyping following disease progression on targeted therapies, particularly second-generation ALK inhibitors. Cancer Discov; 6(10); 1118–33. ©2016 AACR.

See related commentary by Qiao and Lovly, p. 1084.

This article is highlighted in the In This Issue feature, p. 1069
Molecular Mechanisms of Stress-Responsive Changes in Collagen and Elastin Networks in Skin
Authors: Aziz Jazli , Shezali Hafiz , Radzi Zamri , Yahya Noor Azlin , Abu Kassim Noor Hayaty , Czernuszka Jan , Rahman Mohammad Tariqur
Published: July 2016

Collagen and elastin networks make up the majority of the extracellular matrix in many organs, such as the skin. The mechanisms which are involved in the maintenance of homeostatic equilibrium of these networks are numerous, involving the regulation of genetic expression, growth factor secretion, signalling pathways, secondary messaging systems, and ion channel activity. However, many factors are capable of disrupting these pathways, which leads to an imbalance of homeostatic equilibrium. Ultimately, this leads to changes in the physical nature of skin, both functionally and cosmetically. Although various factors have been identified, including carcinogenesis, ultraviolet exposure, and mechanical stretching of skin, it was discovered that many of them affect similar components of regulatory pathways, such as fibroblasts, lysyl oxidase, and fibronectin. Additionally, it was discovered that the various regulatory pathways intersect with each other at various stages instead of working independently of each other. This review paper proposes a model which elucidates how these molecular pathways intersect with one another, and how various internal and external factors can disrupt these pathways, ultimately leading to a disruption in collagen and elastin networks.
Pharmacodynamic Effects of Sucroferric Oxyhydroxide and Sevelamer Carbonate on Vitamin D Receptor Agonist Bioactivity in Dialysis Patients
Authors: Sprague Stuart M. , Covic Adrian C. , Floege Jürgen , Ketteler Markus , Botha Jaco , Chong Edward M. , Rastogi Anjay
Published: July 2016

Background: Many patients with chronic kidney disease are prescribed vitamin D receptor agonists (VDRAs) for the management of secondary hyperparathyroidism. Oral phosphate binders may interact with, and potentially reduce the therapeutic activity of, oral VDRAs. This post hoc analysis of a Phase 3 study evaluated the pharmacodynamic effects of the iron-based phosphate binder sucroferric oxyhydroxide (SFOH) and sevelamer (SEV) carbonate on VDRA activity in dialysis patients. Methods: One thousand and fifty nine patients were randomized to SFOH 1.0-3.0 g/day (n = 710) or SEV 2.4-14.4 g/day (n = 349) for up to 52 weeks. Potential interactions of SFOH and SEV with VDRAs were assessed using serum intact parathyroid hormone (iPTH) concentrations as a pharmacodynamic biomarker. Three populations of SFOH- and SEV-treated patients were analyzed: Population 1 (n = 187), patients taking concomitant stable doses of oral VDRAs only; Population 2 (n = 250), patients taking no concomitant VDRAs; Population 3 (n = 68), patients taking concomitant stable doses of intravenous paricalcitol only. Populations were compared using a mixed-effects model to obtain the least squares mean change in iPTH from baseline to Week 52. Differences between treatment groups were also compared. Results: In Population 1, iPTH decreased from baseline to Week 52 in the SFOH group (-25.3 pg/ml) but increased in the SEV group (89.8 pg/ml) (p = 0.02). In Population 2, iPTH increased to a similar extent in both treatment groups. In Population 3, iPTH concentrations in both treatment groups decreased to a similar degree (-29.6 and -11.4 pg/ml for SFOH and SEV, respectively; p = 0.87). Conclusions: In contrast with SEV, SFOH did not appear to impact the iPTH-lowering effect of oral VDRAs.
As relações entre o estádio do espelho e os transtornos psicomotores
Authors: Barth Luís Fernando Barnetche
Published: July 2016

No presente artigo, o autor busca estudar as relações entre o conceito psicanalítico de estádio do espelho e o aparecimento de transtornos psicomotores em crianças. O trabalho parte do desenvolvimento motor, tal qual é classicamente concebido pela biologia, até propor uma metapsicologia do desenvolvimento. Esta pesquisa é baseada no tratamento psicanalítico de uma criança portadora de Transtorno Específico do Desenvolvimento da Função Motora, servindo de elemento à construção metapsicológica de caso como forma de apresentação dos achados de uma pesquisa psicanal ítica.
Dimensão institucional de uma clínica da queixa escolar: a prática psicanalítica revisitada
Authors: Guirado Marlene
Published: July 2016

O objetivo deste texto é pensar o atendimento da clínica-escola à queixa escolar, considerando que a relação entre quem oferece esse serviço e quem o demanda é uma prática institucional que supõe: uma relação básica e expectativas cruzadas, sobre determinadas pelo contexto. Implicação de assim considerar uma clínica da queixa escolar: fazer cortes que façam pensar os lugares que aí se instituem, as demandas cruzadas e as propostas possíveis nessa compreensão. O alvo é produzir um atendimento que seja, no limite, analítico, e em benefício de quem procura nossos serviços.
Sobre o sujeito da psicanálise
Authors: Burgarelli Cristóvão Giovani
Published: July 2016

Objetiva-se, com este artigo, pensar algumas implicações que advêm da consideração de que, ao incidir no organismo humano, no infans, o significante o constitui como corpolinguagem. Para isso, tomaremos como referencial uma imbricação entre os campos da psicanálise e da linguagem, mais especificamente o que Freud nos apresenta em “Além do princípio do prazer ” e as contribuições que Lacan traz a essa leitura no seminário 20.
Autismo e novas perspectivas clínicas
Authors: Saboia Camila
Published: July 2016

O autismo precoce leva-nos a reelaborar conceitos como o de intersubjetividade baseados na microanálise do comportamento do bebê, cujos resultados revelam uma indiferença, por parte de bebês ditos de riscos autísticos, aos sinais respons áveis pela construção de laços sociais, tais como o reconhecimento da musicalidade da voz e a leitura das express ões maternas. O entrelaçamento dos resultados obtidos pelas Neurociências e pela Psicanálise reforça a noção de que o autismo teria suas origens em um problema de ordem sonora, manifestado no período pré-natal, uma vez que a experiência rítmica seria a base formadora para o senso de vivência e continuidade de ser do indivíduo.
O lúdico no atendimento de crianças com deficiência: uma reflexão sobre a produção cultural na infância
Authors: Takatori Marisa , Bomtempo Edda , Pereira Fernanda De Souza Dalti , Lin Luana Wang , Bansi Luciana Orui , Correia Ricardo Lopes
Published: July 2016

O artigo propõe discutir as atividades que a criança com defici ência realiza durante o processo de terapia ocupacional vistas como produções singulares de cultura e expressão da subjetividade. Para tal, numa investigação onde os campos da subjetividade e do simbolismo estão presentes, utilizou material da experiência clínica com crianças que têm deficiência coletado da leitura de prontuários e dos registros das observa ções vivenciadas pelo terapeuta num diário de campo. Verificou- se a possibilidade de uma reflexão sobre a consideração cultural das produções das crianças, como favorecedoras do seu reconhecimento e da sua participação ativa na realidade compartilhada.
Leitura de bebês
Authors: Jerusalinsky Julieta , Berlinck Manoel Tosta
Published: July 2016

Na clínica com a primeira infância se intervém não só por meio da escuta, mas fundamentalmente por meio de uma leitura - leitura que opera em relação às produções do bebê e também em relação ao modo de seus pais colocarem em ato seu discurso nos cuidados que lhe dirigem. Isto leva a considerar de que modo o olhar do clínico se situa diante do sintoma dado a ver no corpo do bebê, diferenciando seu lugar na observação de bebês do que ocupa em uma clínica que intervém por meio de uma leitura.
Criança psicótica brinca?: considerações acerca do brincar na psicose
Authors: Soares Julia Maciel
Published: July 2016

This paper discusses the playing as a symbolic activity, which is defined as the representation of what is absent. Therefore, to take place, it depends on the separation process. It discusses the playing of psychotic children, for whom the subjective position was structured without the absence inscription. Through the study of two short clinical cases, it examines whether the ludic activity of a psychotic child is, indeed, a playing activity.
O impacto do discurso da ciência na relação professor-aluno: repercussões em psicanálise
Authors: Souza Marcelo Fonseca Gomes de , Pereira Marcelo Ricardo
Published: July 2016

O presente artigo objetiva investigar a repercussão do " Discurso da Ciência" - tal como pensado por Jacques Lacan no " Seminário 17: o avesso da psicanálise" - no universo escolar. Ao destacar o saber como a dominante do Discurso e o Significante- Mestre (S1) como a verdade que o determina, busca-se analisar os impactos de sua assimilação no espaço escolar a partir de dois focos nucleares: o professor - descrito aqui como apenas um técnico que deve apreender conhecimentos e desenvolver competências para sua intervenção prática - e o aluno - que aparece, neste espaço, como duplamente subjugado.
SOBRE A IMPORTÂNCIA DA TRANSMISSÃO PARENTAL DO DESEJO PARA A PSICANÁLISE A PARTIR DE UM CASO DE OBESIDADE INFANTIL
Authors: Lana Garcia de Oliveira Flávia , Darriba Vinícius Anciães
Published: July 2016

Buscamos demonstrar a importância da transmissão parental do desejo na constituição psíquica da criança a partir de Freud e Lacan, apontando para o papel estruturante das funções materna e paterna como transmissores dos operadores simbólicos na regulação do gozo no laço social. Uma situação clínica envolvendo o fenômeno da obesidade infantil nos permite inferir os entraves experimentados por uma criança na subjetivação do seu corpo devido à precariedade simbólica dessas funções. Depreendemos, assim, como uma perturbação discursiva familiar pode repercutir para uma criança em uma significativa fragilização do processo de assunção da diferença sexual e sua inscrição na sucessão geracional.
Produção do fracasso escolar e o furor avaliativo: o sujeito resiste?
Authors: Passone Eric Ferdinando Kanai
Published: July 2016

Pensar o fracasso escolar como acontecimento do sujeito subverte o discurso do fracasso produzido em grande medida pelo fantasma da avaliação "standard" na gestão do ensino. Nessa perspectiva, interrogam-se o furor avaliativo e os discursos acerca da eficácia e qualidade dos sistemas educacionais enquanto dispositivos de domesticação social dos mais novos que acabam por aumentar a psicologização e a medicalização no cotidiano escolar.
Adolescência e síndrome de down na tela
Authors: Zachello Camilla , Paul Fernanda Mantese , Gurski Roselene
Published: July 2016

Este artigo, escrito na forma de ensaio, propõe-se a discutir algumas nuances da passagem adolescente vivida pelos sujeitos portadores da síndrome de Down, a partir de uma leitura/escuta (Iribarry, 2003) da narrativa do filme Colegas (Galvão, 2013). Entendemos que, ao desvelar alguns traços presentes na narrativa, estamos contribuindo para a reflexão acerca da passagem da adolescência com tais sujeitos. Trata-se de um modo de investigação que, ao partir do enlace da tríade psicanálise, educação e cinema, toma as produções da cultura como elementos passíveis de serem lidos/escutados e de produzirem alguma algo novo sobre o campo ao qual se debruça - o tema da adolescência e a síndrome de Down.
Uma acompanhante terapêutica para duas
Authors: Gerab Cristiana Kehdi
Published: July 2016

Este artigo descreve um trabalho de acompanhamento terapêutico com uma adolescente que possui deficiência intelectual. Mas é sua posição subjetiva que está em jogo e é relevante neste trabalho. Discute-se a escuta psicanalítica dos pais enquanto questão essencial para que o acompanhamento com esta adolescente possa acontecer.
Esquecimentos, fantasias e sexualidade infantil: efeitos da autoanálise de Freud
Authors: Costa André Oliveira
Published: July 2016

Durante seu período de autoanálise, normalmente situado pelos estudiosos de sua obra entre os anos de 1897 e 1900, Freud descobriu, através da investigação de seus próprios sonhos e de suas lembranças infantis, os traços fundamentais de nosso inconsciente. Nesse artigo, nos propomos a desdobrar, através dos textos desse período, o processo e o contexto de descoberta que o levou a propor, dentre outros, o esquecimento, a fantasia e a sexualidade infantil como elementos estruturantes para o funcionamento do aparelho psíquico.
Rua da Fronteira, nº 14: fragmentos da singularidade de uma experiência
Authors: Machado Letícia Vier
Published: July 2016

O objetivo deste artigo é relatar uma experiência com a psicanálise aplicada às instituições no estágio profissional realizado na instituição belga orientada pela psicanálise lacaniana, o Courtil. A metodologia de trabalho da instituição se orienta pela perspectiva clínica psicanalítica da prática entre vários, desenvolvida no trabalho em instituições com autistas e psicóticos. O relato se dá em dois tempos, segundo a perspectiva da estagiária: no primeiro momento, explora-se a dinâmica institucional e os lugares ocupados por ela; depois, privilegia-se sua posição subjetiva nas experiências clínicas e no cotidiano com as crianças.
Entrando na linguagem
Authors: Queiroz Telma Corrêa da Nóbrega
Published: July 2016

A linguagem sobrevém da necessidade de conservar o objeto além da satisfação da necessidade, sendo, portanto, resultado da atividade pulsional. Nesse processo, o objeto da pulsão invocante e o da pulsão alimentar se substituem um ao outro. A articulação da psicolingüística com a psicanálise ajuda a compreender melhor como isso acontece na medida em que uma observa os comportamentos e a outra supõe desejos subjacentes a esses comportamentos, revelando que todos os comportamentos do bebê são o reflexo de sua atividade pulsional e de sua entrada progressiva na linguagem. A palavra faz com que os objetos perdurem e que possam ser reconhecidos.
A infância que inventamos e as escolas de ontem e de hoje;;
Authors: Lajonquière Leandro De
Published: July 2016

Contribuição ao debate atual sobre a invenção e o desaparecimento da infância graças a ferramentas conceituais psicanalíticas.
Infâncias Públicas. Não é justo
Authors: Mercedes Minnicelli
Published: July 2016

Infâncias públicas. Não é justo é o título do livro que publicaremos em breve e no qual exporemos o desenvolvimento de uma investigação psicanalítica que não seguiu os caminhos habituais. O discurso da "menoridade" é analisado como a outra face da Infância Moderna
Os tempos do sujeito e do outro: Narração, discurso e pulsão;;
Authors: Poli Maria Cristina
Published: July 2016

As narrativas produzidas em análise são interpretadas a partir do operador clínico, proposto por Lacan, da alienação/separação. Nesta proposição, as diferentes posições do sujeito nas narrativas originárias podem ser lidas na interface do campo do sujeito com o campo do Outro. O tempo em causa nas narrativas é, então, o do ritmo pulsional e o conteúdo da narrativa, o corpus representacional constituído pelo discurso. Movimentos de alienação/separação entre sujeito e Outro que constituem o desdobramento das posições do sujeito da enunciação nas várias versões em que o fantasma originário pode se apresentar.
Sobre imaginário, mitos e arquétipos: exercício aplicado à narrativa audiovisual
Authors: Budag Fernanda Elouise
Published: July 2016

Trazemos para o centro de nossa discussão o conceito de imagináriojustamente pela relevância que acreditamos que ganha na contemporaneidade.Para estudar essa esfera, assumimos a metodologia de estudo do imaginário,a mitocrítica, desenvolvida por Durand (1985). Portanto, após introduzirmos aordem imaginária e sua estruturação e explorarmos os preceitos da mitocrítica,apresentamos a série objeto de nosso estudo, Once upon a time, e propomosum exercício de aplicação da metodologia à série. Entendemos que a narrativaaudiovisual promove imagens que interiorizamos, consistindo em fonteprivilegiada para a construção de imaginários e, consequentemente, substratopertinente para aplicação do método em questão.
Periferia ao Vivo: Democratização da Mídia e Socialização da Informação por meio do hip-hop Maranhense
Authors: Santos Rosenverck Estrela
Published: July 2016

Este texto discute as relações entre o movimento hip-hop e a democratização da mídia, por meio do movimento “Quilombo Urbano”. Reflete o processo de formação do hip-hop em São Luís do Maranhão no contexto de periferização da cidade. Analisa a formação da identidade étnico-racial dos jovens envolvidos nesse movimento e a produção de difusão de informações por meio de suas atividades político-cultuais e da criação, organização e participação em programas de rádios comunitárias em bairros pobres e negros da capital maranhense. Para tanto, definimos o hip-hop como um movimento político-cultural e compreendemos que o movimento hip-hop maranhense, por meio do “Quilombo Urbano”, se constitui como uma possibilidade de identificação e mobilização para parcela considerável da juventude negra e pobre que buscam um agir coletivo.
Os Cinemas Que Falam Português: O Conceito De Cinema Nacional, Identidade e Resistência
Authors: Mendonça Leandro José Luz Riodades
Published: July 2016

O presente artigo apresenta questões em torno do conceito de cinema nacional e suas formas de existência/resistência. Articula a dimensão espacial como limitante para consumo dos objetos culturais pois estes não têm livre circulação comercial. As identidades nacionais continuam a exercer pressão sobre o cinema e participam da produção da representação que opera mecanismos de inclusão ou exclusão dentro de um espaço geográfico. Reflete sobre a produção cultural e as artes pois parte da observação dos dados imediatos da realidade pensada parte de constrangimentos limitações a capacidade real de produzir filmes. As limitações são, por exemplo, capacidade técnica e treinamento diferenciados e uma desigual capacidade de financiamento e circulação. Estes elementos redundam em produtos estéticos marcadamente diferentes.