bluuebunny/crossref_metadata_2025 huggingface dataset:
A closed-form analytical model for predicting 3D boundary layer displacement thickness for the validation of viscous flow solvers
Authors: Kumar V. R. Sanal , Sankar Vigneshwaran , Chandrasekaran Nichith , Saravanan Vignesh , Natarajan Vishnu , Padmanabhan Sathyan , Sukumaran Ajith , Mani Sivabalan , Rameshkumar Tharikaa , Nagaraju Doddi Hema Sai , Vysaprasad Krithika , Sharan Sharad , Murugesh Pavithra , Shankar S. Ganesh , Nejaamtheen Mohammed Niyasdeen , Baskaran Roshan Vignesh , Rahman Mohamed Rafic Sulthan Ariff , Harisrinivasan Ukeshkumar , Srinivasan Vivek
Published: February 2018

A closed-form analytical model is developed for estimating the 3D boundary-layer-displacement thickness of an internal flow system at the Sanal flow choking condition for adiabatic flows obeying the physics of compressible viscous fluids. At this unique condition the boundary-layer blockage induced fluid-throat choking and the adiabatic wall-friction persuaded flow choking occur at a single sonic-fluid-throat location. The beauty and novelty of this model is that without missing the flow physics we could predict the exact boundary-layer blockage of both 2D and 3D cases at the sonic-fluid-throat from the known values of the inlet Mach number, the adiabatic index of the gas and the inlet port diameter of the internal flow system. We found that the 3D blockage factor is 47.33 % lower than the 2D blockage factor with air as the working fluid. We concluded that the exact prediction of the boundary-layer-displacement thickness at the sonic-fluid-throat provides a means to correctly pinpoint the causes of errors of the viscous flow solvers. The methodology presented herein with state-of-the-art will play pivotal roles in future physical and biological sciences for a credible verification, calibration and validation of various viscous flow solvers for high-fidelity 2D/3D numerical simulations of real-world flows. Furthermore, our closed-form analytical model will be useful for the solid and hybrid rocket designers for the grain-port-geometry optimization of new generation single-stage-to-orbit dual-thrust-motors with the highest promising propellant loading density within the given envelope without manifestation of the Sanal flow choking leading to possible shock waves causing catastrophic failures.
Establishing microbial baselines to identify indicators of coral reef health
Authors: Glasl Bettina , Bourne David G , Frade Pedro R , Webster Nicole S
Published: February 2018

Microorganisms make a significant contribution to reef ecosystem health and resilience via their critical role in mediating nutrient transformations, their interactions with macro-organisms and their provision of chemical cues that underpin the recruitment of diverse reef taxa. However, environmental changes often cause compositional and functional shifts in microbial communities that can have flow-on consequences for microbial-mediated processes. These microbial alterations may impact the health of specific host organisms and can have repercussions for the functioning of entire coral ecosystems. Assessing changes in reef microbial communities should therefore provide an early indicator of ecosystem impacts and would underpin the development of diagnostic tools that could help forecast shifts in coral reef health under different environmental states. Monitoring, management and active restoration efforts have recently intensified and diversified in response to global declines in coral reef health. Here we propose that regular monitoring of coral reef microorganisms could provide a rapid and sensitive platform for identifying declining ecosystem health that can complement existing management frameworks. By summarising the most common threats to coral reefs, with a particular focus on the Great Barrier Reef, and elaborating on the role of microbes in coral reef health and ecosystem stability, we highlight the diagnostic applicability of microbes in reef management programs. Fundamental to this objective is the establishment of microbial baselines for Australia's coral reefs.
Habitat Preference and Reproduction of Feral House Mice, Mus musculus, during Plague and Non-Plague Situations in Western Australia
Authors: Chapman Andrew
Published: February 2018

In Western Australia feral Mus musculus are well established in the southern half of the State, including remote, arid desert situations. In the South West Division Mus have a distinct spring-summer breeding period, with some breeding in autumn after favourable climatic conditions. A plague in autumn 1975 is described and abundance, fecundity, trapping behaviour and habitat selection are compared between plague and non-plague situations. It is considered that abundant rainfall during the two preceding years caused the plague. Decline of the plague coincided with the onset of winter; there is some evidence to suggest that shelter more than food limited numbers, but the decline was probably also influenced by intrinsic factors. In wheatbelt areas of Western Australia Mus are most abundant in samphire heaths.
Editing out five
Serpina1
paralogs to create a mouse model of genetic emphysema
Authors: Borel Florie , Sun Huaming , Zieger Marina , Cox Andrew , Cardozo Brynn , Li Weiying , Oliveira Gabriella , Davis Airiel , Gruntman Alisha , Flotte Terence R. , Brodsky Michael H. , Hoffman Andrew M. , Elmallah Mai K. , Mueller Christian
Published: February 2018

Significance

Chronic obstructive pulmonary disease affects 10% of the worldwide population, and the leading genetic cause is a genetic disease, α-1 antitrypsin (AAT) deficiency. Humans have only one gene that codes for the AAT protein, but mice have up to six, which made it impossible for decades to create a mouse model of the disease. Here we succeeded in creating this mouse model using CRISPR technology to target all of the mouse genes at once. Importantly, this mouse model spontaneously develops lung disease and recapitulates many aspects of the human disease. We anticipate that this model will be highly relevant not only to the preclinical development of therapeutics for AAT deficiency, but also to emphysema and smoking research.
Structure-based discovery of selective positive allosteric modulators of antagonists for the M
2
muscarinic acetylcholine receptor
Authors: Korczynska Magdalena , Clark Mary J. , Valant Celine , Xu Jun , Moo Ee Von , Albold Sabine , Weiss Dahlia R. , Torosyan Hayarpi , Huang Weijiao , Kruse Andrew C. , Lyda Brent R. , May Lauren T. , Baltos Jo-Anne , Sexton Patrick M. , Kobilka Brian K. , Christopoulos Arthur , Shoichet Brian K. , Sunahara Roger K.
Published: February 2018

Significance

The orthosteric binding sites of the five muscarinic acetylcholine receptor (mAChR) subtypes are highly conserved, making the development of selective antagonists challenging. The allosteric sites of these receptors are more variable, allowing one to imagine allosteric modulators that confer subtype selectivity, which would reduce the major off-target effects of muscarinic antagonists. Accordingly, a large library docking campaign was prosecuted seeking unique positive allosteric modulators (PAMs) for antagonists, ultimately revealing a PAM that substantially potentiates antagonist binding leading to subtype selectivity at the M
2
mAChR. This study supports the feasibility of discovering PAMs that can convert an armamentarium of potent but nonselective G-protein–coupled receptor (GPCR) antagonist drugs into subtype-selective reagents.
Perspectival representation and fallacies in metaethics
Authors: Kölbel Max
Published: February 2018

The prevailing theoretical framework for theorising about representation construes all representation as involving objective representational contents. This classic framework has tended to drive philosophers either to claim that evaluative judgements are representations and therefore objective, or else to claim that evaluative judgements are not really representations, because they are not objective. However, a more general, already well-explored framework is available, which will allow theorists to treat evaluative judgements as full-fledged representations (thus doing justice to their representational aspects) while leaving open whether they are objective. Such a more general conception of representational content is exemplified, e.g. by Lewis's ‘centred contents’ and Gibbard's framework of ‘contents of judgement’, thus it is not new. I shall start in §1 by introducing the more general framework of perspectival contents and then illustrate in §2 how awareness of it can help expose the fallaciousness of certain widely used forms of argumentation in metaethics.
Reasons for emotion and moral motivation
Authors: Blackman Reid
Published: February 2018

Internalism about normative reasons is the view that an agent’s normative reasons depend on her motivational constitution. On the assumption that there are reasons for emotion I argue that (a) externalism about reasons for emotion entails that all rational agents have reasons to be morally motivated and (b) internalism about reasons for emotion is implausible. If the arguments are sound we can conclude that all rational agents have reasons to be morally motivated. Resisting this conclusion requires either justifying internalism about reasons for emotion in a way hitherto unarticulated or giving up on reasons for emotion altogether.
Immunoaffinity‐based isolation of melanoma cell‐derived exosomes from plasma of patients with melanoma
Authors: Sharma Priyanka , Ludwig Sonja , Muller Laurent , Hong Chang Sook , Kirkwood John M , Ferrone Soldano , Whiteside Theresa L.
Published: February 2018

Tumour‐derived exosomes (TEX) are a subset of extracellular vesicles (EVs) present in body fluids of patients with cancer. The role of this exosome subset in melanoma progression has been of interest ever since ex vivo studies of exosomes produced by melanoma cell lines were shown to suppress anti‐melanoma immune responses. To study the impact of melanoma‐derived exosomes (MTEX) present in patients’ plasma on melanoma progression, isolation of MTEX from total plasma exosomes is necessary. We have developed an immunoaffinity‐based method for MTEX capture from plasma of melanoma patients. Using mAb 763.74 specific for the CSPG4 epitope uniquely expressed on melanoma cells, we separated MTEX from non‐tumour cell‐derived exosomes and evaluated the protein cargo of both fractions by quantitative flow cytometry. Melanoma‐associated antigens were carried by MTEX but were not detectable in exosomes produced by normal cells. Separation of plasma‐derived MTEX from non‐MTEX provides an opportunity for future evaluation of MTEX as potential biomarkers of melanoma progression and as surrogates of melanoma in tumour liquid biopsy studies.
A model for AGN variability on multiple time-scales
Authors: Sartori Lia F , Schawinski Kevin , Trakhtenbrot Benny , Caplar Neven , Treister Ezequiel , Koss Michael J , Megan Urry C , Zhang Ce
Published: February 2018

We present a framework to link and describe active galactic nuclei (AGN) variability on a wide range of time-scales, from days to billions of years. In particular, we concentrate on the AGN variability features related to changes in black hole fuelling and accretion rate. In our framework, the variability features observed in different AGN at different time-scales may be explained as realisations of the same underlying statistical properties. In this context, we propose a model to simulate the evolution of AGN light curves with time based on the probability density function (PDF) and power spectral density (PSD) of the Eddington ratio (L/LEdd) distribution. Motivated by general galaxy population properties, we propose that the PDF may be inspired by the L/LEdd distribution function (ERDF), and that a single (or limited number of) ERDF+PSD set may explain all observed variability features. After outlining the framework and the model, we compile a set of variability measurements in terms of structure function (SF) and magnitude difference. We then combine the variability measurements on a SF plot ranging from days to Gyr. The proposed framework enables constraints on the underlying PSD and the ability to link AGN variability on different time-scales, therefore providing new insights into AGN variability and black hole growth phenomena.
Influence of Residual Disease Following Surgical Resection in Newly Diagnosed Glioblastoma on Clinical, Neurocognitive, and Patient Reported Outcomes
Authors: Hall William A , Pugh Stephanie L , Wefel Jeffrey S , Armstrong Terri S , Gilbert Mark R , Brachman David G , Werner-Wasik Maria , Wendland Merideth M , Brown Paul D , Chao Samuel T , Roof Kevin S , Robins H Ian , Mehta Minesh P , Curran Walter J , Movsas Benjamin
Published: February 2018

BACKGROUND

The influence of subtotal resection (STR) on neurocognitive function (NCF), quality of life, and symptom burden in glioblastoma is unknown. If bevacizumab preferentially benefits patients with STR is unknown.

OBJECTIVE

To examine these uncertainties.

METHODS

NCF and patient reported outcomes (PRO) were prospectively collected in NRG Oncology RTOG 0525 and 0825. Changes in NCF and PRO measures from baseline to prespecified times were examined by Wilcoxon test, and mixed effects longitudinal modeling, to assess differences between patients who received STR vs gross-total resection. Changes were also compared among STR patients on 0825 receiving placebo vs bevacizumab to assess for a preferential therapeutic effect. Overall survival between STR and gross-total resection patients was compared using the Kaplan–Meier method.

RESULTS

A total of 427 patients were eligible with STR present in 37%. At baseline, patients with STR had worse NCF, worse MD Anderson Symptom Inventory Brain Tumor Neurological Factor ratings (P = .004), and European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (P = .002). Longitudinal multivariate analysis associated STR with worse NCF (Hopkins Verbal Learning Test–Revised Delayed Recognition [P = .048], Trail Making Test Part A [P = .035], and Controlled Oral Word Association [P = .049]). One hundred eighty-three STR patients from 0825 were analyzed (89 bevacizumab, 94 placebo); bevacizumab failed to demonstrate improvement in select NCF or PRO measures.

CONCLUSION

STR patients had worse NCF and PROs before therapy. During adjuvant therapy, STR patients had worse objective NCF, despite accounting for tumor location. STR did not result in a detriment to OS. The addition of bevacizumab did not preferentially improve PRO or NCF outcomes in STR patients.
High Pressure in Virtual Postcoiling Model is a Predictor of Internal Carotid Artery Aneurysm Recurrence After Coiling
Authors: Nambu Iku , Misaki Kouichi , Uchiyama Naoyuki , Mohri Masanao , Suzuki Takashi , Takao Hiroyuki , Murayama Yuichi , Futami Kazuya , Kawamura Tomoki , Inoguchi Yasushi , Matsuzawa Teruo , Nakada Mitsutoshi
Published: February 2018

BACKGROUND

Hemodynamic factors play a crucial role in the recurrence of intracranial aneurysms after coiling. However, the strongest factor for predicting recurrence remains unclear because each risk factor has been investigated and reported separately.

OBJECTIVE

To clarify the strongest predictor of recurrence with computational fluid dynamics (CFD).

METHODS

Using pretreatment patient-specific 3-dimensional rotational angiography data of 50 internal carotid artery (ICA) aneurysms (7 recanalized, 43 stable) treated with endovascular coiling, we created a precoiling model and a virtual postcoiling model produced by manually cutting the aneurysm by the flat plane corresponding to the virtual coil surface. We conducted CFD analysis to investigate inflow dynamics in the precoiling model and pressure difference and wall shear stress on the virtual coil surface. The pressure difference was calculated by subtracting average pressure at the proximal ICA from the maximum pressure at the coil surface and dividing by dynamic pressure at the proximal ICA for normalization. We compared hemodynamic parameters in both models between recanalized and stable aneurysms.

RESULTS

Compared with stable aneurysms, recanalized aneurysms showed a significantly larger inflow area and higher inflow rate in the precoiling model (P = .016, .028), and higher pressure difference at the coil surface in the postcoiling model (P < .001). The receiver-operating characteristic analysis showed that the area under the curve value for the pressure difference (0.967) was superior to that of other evaluated parameters.

CONCLUSION

The pressure difference in the virtual postcoiling model may be a strong predictor of recurrence after coiling.
Neuropsychological Changes in Patients Undergoing Treatment of Unruptured Intracranial Aneurysms
Authors: Caveney Angela F , Langenecker Scott A , Pandey Aditya S , Farah Laura B , Ortiz J Alexis , Huq Nadia , Bhaumik Runa , Thompson B Gregory , Giordani Bruno J , Auer Donna , Morgenstern Lewis B
Published: February 2018

BACKGROUND

Evaluation of differences in neuropsychological outcomes in patients undergoing surgical clipping (SC) vs endovascular coiling (EC) for unruptured cerebral aneurysms is essential in guiding patients seeking treatment of asymptomatic cerebral aneurysms.

OBJECTIVE

To perform a prospective longitudinal analysis of neuropsychological outcomes in patients who underwent microsurgery or coiling for unruptured cerebral aneurysms.

METHODS

SC (50 patients), EC (35 patients), and healthy controls (43 individuals) were included. A detailed neuropsychological evaluation was performed at baseline and at 2 wk, 3 mo, 6 mo, and 12 mo. Student's t-test was utilized for comparing neuropsychological outcomes among the 3 groups. A mixed-effects model allowed for evaluation of neuropsychological outcome changes among the groups over time.

RESULTS

Both the SC and EC groups had nonsignificant differences in procedure-related complications. SC patients had the greatest initial declines in short-term memory, fine motor control, and executive functioning; however, these patients also recovered to a greater degree in neuropsychological functionality. Over the next year, all groups achieved similar neuropsychological outcomes with no significant differences among groups.

CONCLUSION

Whereas the initial decline in neuropsychological functioning was greater for SC patients, 1 yr after treatment there was no significant difference in neuropsychological outcome among the SC, EC, and healthy control groups.
Supratentorial Cavernous Malformations Involving the Corticospinal Tract and Sensory Motor Cortex: Treatment Strategies, Surgical Considerations, and Outcomes
Authors: Skrap Miran , Vescovi Maria Caterina , Pauletto Giada , Maieron Marta , Tomasino Barbara , Bagatto Daniele , Tuniz Francesco
Published: February 2018

BACKGROUND

Cavernous malformations (CMs) are congenital malformations and may be located anywhere in the brain. We present a series of CMs located close to or inside of the motor-sensory cortex or corticospinal tract (CST) with clinical onset due to hemorrhage or mass effect. In such cases, surgery becomes an acceptable option.

OBJECTIVE

To evaluate the role of diffusion tensor imaging (DTI), functional-magnetic-resonance imaging (fMRI), intraoperative neurophysiological monitoring, neuronavigation, and brain-mapping and the clinical results of surgical treatment of CMs in this critical location.

METHODS

The study included 54 patients harboring 22 cortical and 32 deep locations. This series was distinct because in group I, where the DTI was not obtained, and in the group II, where this evaluation was performed.

RESULTS

The postoperative permanent morbidity rate was 4% in the historical group for the deeper CMs, and there was no morbidity in the second group. DTI and fMRI permitted us to estimate the distance between the CMs and both the cortical activation cluster and the pyramidal tract. These data, in addition to intraoperative mapping and monitoring, made it necessary for us to perform a partial resection in 2 cases in the second series.

CONCLUSION

CMs are congenital lesions and CST fibers can run directly on their surface. Integration of fMRI and DTI data with intraoperative functional monitoring and direct cortical and subcortical mapping are mandatory to accomplish an optimal resection, tailoring the best surgical approach to the acceptable morbidity. A subtotal resection could be considered an option for deep locations.
Sitting Together And Reaching To Play (START-Play): Protocol for a Multisite Randomized Controlled Efficacy Trial on Intervention for Infants With Neuromotor Disorders
Authors: Harbourne Regina T , Dusing Stacey C , Lobo Michele A , Westcott-McCoy Sarah , Bovaird James , Sheridan Susan , Galloway James C , Chang Hui-Ju , Hsu Lin-Ya , Koziol Natalie , Marcinowski Emily C , Babik Iryna
Published: February 2018

Background

There is limited research examining the efficacy of early physical therapy on infants with neuromotor dysfunction. In addition, most early motor interventions have not been directly linked to learning, despite the clear association between motor activity and cognition during infancy.

Objective

The aim of this project is to evaluate the efficacy of Sitting Together And Reaching To Play (START-Play), an intervention designed to target sitting, reaching, and motor-based problem solving to advance global development in infants with motor delays or neuromotor dysfunction.

Design

This study is a longitudinal multisite randomized controlled trial. Infants in the START-Play group are compared to infants receiving usual care in early intervention (EI).

Setting

The research takes place in homes in Pennsylvania, Delaware, Washington, and Virginia.

Participants

There will be 140 infants with neuromotor dysfunction participating, beginning between 7 to 16 months of age. Infants will have motor delays and emerging sitting skill.

Intervention

START-Play provides individualized twice-weekly home intervention for 12 weeks with families to enhance cognition through sitting, reaching, and problem-solving activities for infants. Ten interventionists provide the intervention, with each child assigned 1 therapist.

Measurements

The primary outcome measure is the Bayley III Scales of Infant Development. Secondary measures include change in the Early Problem Solving Indicator, change in the Gross Motor Function Measure, and change in the type and duration of toy contacts during reaching. Additional measures include sitting posture control and parent-child interaction.

Limitations

Limitations include variability in usual EI care and the lack of blinding for interventionists and families.

Conclusions

This study describes usual care in EI across 4 US regions and compares outcomes of the START-Play intervention to usual care.
Impact of Endometriosis on Risk of Further Gynaecological Surgery and Cancer: A National Cohort Study
Authors: Saraswat L. , Ayansina D. , Cooper K. G. , Bhattacharya S. , Horne A. W. , Bhattacharya S.
Published: February 2018

(Abstracted from BJOG 2018;125(1):64–72)

The mainstay for the diagnosis and treatment of endometriosis is surgery. After the initial surgery, women often undergo multiple operations in an attempt to alleviate persistent symptoms of pain and infertility.
Drug Interactions Between Non-Rifamycin Antibiotics and Hormonal Contraception: A Systematic Review
Authors: Simmons Katharine B. , Haddad Lisa B. , Nanda Kavita , Curtis Kathryn M.
Published: February 2018

(Abstracted from Am J Obstet Gynecol 2018;218(1):88–97.e14)

Hormonal contraception (HC) is used by millions of women worldwide to prevent unintended pregnancies. Because antibiotics are commonly used by reproductive-aged women, it is important to understand whether drug interactions between HC and antibiotics can contribute to HC failure or pose safety concerns.
Maternal Deaths in the Nordic Countries
Authors: Vangen Siri , Bødker Birgit , Ellingsen Liv , Saltvedt Sissel , Gissler Mika , Geirsson Reynir T. , Nyfløt Lill T.
Published: February 2018

(Abstracted from Acta Obstet Gynecol Scand 2017;96(9):1112–1119)

Underreporting of maternal deaths is a global issue and can hinder the designing and development of preventive and management practices for reducing the maternal mortality ratio (MMR). Although the MMR is among the lowest in the Nordic countries, there is still opportunity to further reduce the rate of direct or indirect maternal deaths.
Effect of Post–Cesarean Delivery Oral Cephalexin and Metronidazole on Surgical Site Infection Among Obese Women: A Randomized Clinical Trial
Authors: Valent Amy M. , DeArmond Chris , Houston Judy M. , Reddy Srinidhi , Masters Heather R. , Gold Alison , Boldt Michael , DeFranco Emily , Evans Arthur T. , Warshak Carri R.
Published: February 2018

(Abstracted from JAMA 2017;318(11):1026–1034)

Surgical site infection (SSI) is a major complication of cesarean delivery, and the risk of SSI increases with obesity despite recommended preoperative antibiotic regimens. This randomized clinical trial aimed to compare the efficacy of postoperative, prophylactic oral cephalexin plus metronidazole with standard preoperative intravenous cephalosporin alone on SSI among obese women after cesarean delivery.
Metformin, the Aspirin of the 21st Century: Its Role in Gestational Diabetes Mellitus, Prevention of Preeclampsia and Cancer, and the Promotion of Longevity
Authors: Romero Roberto , Erez Offer , Hüttemann Maik , Maymon Eli , Panaitescu Bogdan , Conde-Agudelo Agustin , Pacora Percy , Yoon Bo Hyun , Grossman Lawrence I.
Published: February 2018

(Abstracted from Am J Obstet Gynecol 2017;217(3):282–302)

Metformin (dimethylbiguanide hydrochloride) was initially introduced as an antidiabetic agent; however, in recent years, it has shown a wide array of beneficial effects ranging from cancer therapy to extending longevity. As a gestational antidiabetic agent, metformin has compared favorably to insulin by showing a significantly reduced frequency of neonatal hyperglycemia, large-for-gestational-age neonates, and admissions to a neonatal intensive care unit compared with those treated with insulin.
Genetic Associations With Gestational Duration and Spontaneous Preterm Birth
Authors: Zhang Ge , Feenstra Bjarke , Bacelis Jonas , Liu Xueping , Muglia Lisa M. , Juodakis Julius , Miller Daniel E. , Litterman Nadia , Jiang Pan-Pan , Russell Laura , Hinds David A. , Hu Youna , Weirauch Matthew T. , Chen Xiaoting , Chavan Arun R. , Wagner Günter P. , Pavličev Mihaela , Nnamani Mauris C. , Maziarz Jamie , Karjalainen Minna K. , Ramet Mika , Sengpiel Verena , Geller Frank , Boyd Heather A. , Palotie Aarno , Momany Allison , Bedell Bruce , Ryckman Kelli K. , Huusko Johanna M. , Forney Carmy R. , Kottyan Leah C. , Hallman Mikko , Teramo Kari , Nohr Ellen A. , Davey Smith George , Melbye Mads , Jacobsson Bo , Muglia Louis J.
Published: February 2018

(Abstracted from N Engl J Med 2017;377:1156–1167)

Preterm birth, caused by idiopathic onset of uterine contractions or rupture of fetal membranes, is a major risk factor for death in neonates and children younger than 5 years. Although there is evidence that preterm birth and gestational duration are affected by both maternal and fetal genomes, robust associations with genetic variations are still not established.
Genomic Microarray in Fetuses With Early Growth Restriction: A Multicenter Study
Authors: Borrell Antoni , Grande Maribel , Meler Eva , Sabrià Joan , Mazarico Edurne , Muñoz Anna , Rodriguez-Revenga Laia , Badenas Cèlia , Figueras Francesc
Published: February 2018

(Abstracted from Fetal Diagn Ther 2017;42:174–180)

Literature has shown that conventional chromosomal anomalies can account for up to 19% of fetal growth restrictions (FGRs) when those with anomalies are included. The majority of these anomalies are triploidy if the fetus is less than 26 weeks and trisomy 18 when equal to or greater than 26 weeks' gestation.
High Gonadotropin Dosage Does Not Affect Euploidy and Pregnancy Rates in IVF PGS Cycles With Single Embryo Transfer
Authors: Barash Oleksii O. , Hinckley Mary D. , Rosenbluth Evan M. , Ivani Kristen A. , Weckstein Louis N.
Published: February 2018

(Abstracted from Hum Reprod 2017;32:2209–2217)

The most effective and reliable method for embryo selection in in vitro fertilization (IVF) cycles is preimplantation genetic screening (PGS). There is a significant decrease in euploidy and blastulation rates with increasing maternal age.
Neuroinflammation and Central Sensitization in Chronic and Widespread Pain
Authors: Ji Ru-Rong , Nackley Andrea , Huh Yul , Terrando Niccolò , Maixner William
Published: February 2018

Chronic pain is maintained in part by central sensitization, a phenomenon of synaptic plasticity, and increased neuronal responsiveness in central pain pathways after painful insults. Accumulating evidence suggests that central sensitization is also driven by neuroinflammation in the peripheral and central nervous system. A characteristic feature of neuroinflammation is the activation of glial cells, such as microglia and astrocytes, in the spinal cord and brain, leading to the release of proinflammatory cytokines and chemokines. Recent studies suggest that central cytokines and chemokines are powerful neuromodulators and play a sufficient role in inducing hyperalgesia and allodynia after central nervous system administration. Sustained increase of cytokines and chemokines in the central nervous system also promotes chronic widespread pain that affects multiple body sites. Thus, neuroinflammation drives widespread chronic pain via central sensitization. We also discuss sex-dependent glial/immune signaling in chronic pain and new therapeutic approaches that control neuroinflammation for the resolution of chronic pain.
Hand infections
Authors: Henry Mark
Published: February 2018

The integument provides only a limited barrier to protect the multiple functional structures of the hand from infection by common bacteria and other rare organisms. If infection is limited to just skin cellulitis, then antibiotics and careful monitoring may be all that is needed. Once bacteria become trapped in a deeper soft-tissue space and form an abscess then debridement must be performed to evacuate the purulence and necrotic tissue. Specialized compartments in the hand such as the pulp space, nail folds, joint cavities, and tendon sheaths facilitate bacterial containment and abscess formation, rendering immune response less effective. Osteomyelitis can originate from direct penetration or spread from an adjacent soft-tissue infection. Orthopaedic devices foster the development of a biofilm that can harbor bacteria, making resolution more difficult. The surgeon should obtain tissue for laboratory analysis at the deep infection site and subsequently administer empiric antibiotics while awaiting culture results. Greater duration of antibiotics is needed for infections of synovial tissues and bone. Unique infections caused by rare organisms may affect the hand, requiring recognition based on specific clinical features and confirmation by specialized laboratory testing.
A novel method for fixation of Weber B distal fibular fractures: a biomechanical comparative study of posterolateral versus lateral neutralization plating
Authors: El-Wahab Reda Abd Mohammed , Kotb Ahmed , Salem Eid Ahmed , El-Gammaz Shady Mohamed , El-Sabbagh Adel Mohamed Moneeb
Published: February 2018

Background:

In this biomechanical study, a new technique of posterolateral plating is compared with lateral plating fixation method for Weber type B ankle fractures.

Methods:

Ten dry fibulae were osteotomized obliquely to simulate a Weber B lateral malleolar fracture. Specimens were divided randomly into two groups: five fibulae were fixed using a lateral plate (Group 1), while the remaining fibulae were fixed with a posterolateral plate (Group 2). The fixed bones were tested for axial load and torsion to failure using a servohydraulic axial compression-distraction device.

Results:

The mean force required to disrupt the fracture fixation in group 2 (54.98 Nm) was significantly higher than in group 1 (21.94 Nm) [P-value=0.028]. The mean angular rotation to failure in group 1 (18.938 degrees) was significantly lower than in group 2 (33.66 degrees) [P-value=0.047]. A highly significant difference in favor of group 2 was reported when distal-end (osteotomized and fixed) torque to failure for each specimen was compared with the corresponding proximal-end (intact) in both groups [P-value=0.009].

Conclusions:

The newly developed technique of posterolateral plating for Weber B fractures has shown improved biomechanical properties over conventional lateral plating and can be used for fixation of such fractures.
Radial Shaft Convergence in Distal Radius Fractures: Diagnosis and Treatment
Authors: Tordjman Daniel , Hinds Richard M. , Yang S. Steven , Capo John T.
Published: February 2018

Radial shaft convergence in distal radius fractures is often misdiagnosed. This common deformation is often associated with a radial translation of the distal fragment. This parameter has to be corrected because of the increased risk of distal radioulnar joint instability due to detensioning of the distal interosseous membrane if there is an associated triangular fibrocartilage complex lesion. A new radiologic sign for diagnosis of proximal radius convergence during distal radius fracture is presented as well as technical tips for correction of this deformity.
The Medial Stabilized Knee Guides Knee Motion
Authors: Canham Colin D. , Incavo Stephen J.
Published: February 2018

Medial pivot kinematics describes the normal axial rotation of the lateral compartment of the knee about the inherently more constrained medial compartment that occurs during flexion and extension. Medial stabilized total knee arthroplasty designs replicate the asymmetric medial-lateral constraint profile of the native knee and can closely recreate normal knee kinematics in vivo. The highly conforming medial articulation provides sagittal stability that substitutes for the posterior cruciate ligament without a cam-post mechanism and serves as a pivot point about which the lateral compartment rotates during flexion and extension. Impressive clinical results and excellent long-term survivorship offer a compelling argument for the use of medial stabilized implants during primary total knee arthroplasty.
Health Policy and Financial Issues Related to New Total Knee Arthroplasty Technology
Authors: Andrawis John P. , Bozic Kevin J.
Published: February 2018

As demand for knee replacement surgery continues to rise, new technologies continue to be introduced with the hopes of improving total knee arthroplasty outcomes. As new value based health care models are introduced, the ability to pay for these new technologies will likely be impacted. Because of past implant failures and limitations, it will be important for providers to use registries to evaluate both the safety and outcomes of new knee arthroplasty designs.
Why All Tibial Polyethylene Bearings are Not the Same?
Authors: Varadarajan Kartik M. , Oral Ebru , Muratoglu Orhun K. , Freiberg Andrew A.
Published: February 2018

Important differences exist in both the materials and geometric forms of tibial bearings across total knee implant systems on the market. The extent of crosslinking, sterilization methods, mechanical/thermal treatment methods used for management of free radicals, the amount of incorporated antioxidants, and the methods for incorporation of antioxidants, are some of the material variables, which may affect bearing clinical performance. Despite initial concerns about increased fatigue damage and failure with crosslinked ultra high molecular weight polyethylene developed to reduce the incidence of osteolysis, their utilization now constitutes close to 50% of tibial bearings in primary operations. This is based on long-term clinical data, which show equivalent or better performance in revisions due to aseptic loosening compared with conventional materials. Similarly, bearing conformity, modularity and mobility, are important geometric elements influencing polyethylene wear and failure. With regard to conformity, conventional wisdom has favored more conforming designs. However, growing body of evidence suggests potential for improved wear performance with less conforming designs enabled by modern polyethylene processing techniques. Long-term clinical data show excellent outcomes for all-polyethylene bearings, which may assume an enhanced role in total knee replacement in the future. In contrast, modern fixed-bearing designs seem to outperform mobile-bearing designs in the long run. Consequently, the use of the mobile bearings has declined over time, and currently they account for about 7% of primary knee replacements.
Cementless TKA: Past, Present, and Future
Authors: Kwong Louis M. , Schneiderman Brian A.
Published: February 2018

The last 4 decades have seen an evolution in the application of cementless technology for the biological fixation of implants in total knee arthroplasty (TKA). Although first generation systems demonstrated variability in performance with many early failures because of aseptic loosening, advances in material science, tribology, and improved knowledge of knee kinematics has since allowed contemporary primary cementless total knee systems to perform at levels that approach or exceed that associated with cemented fixation. Published series at 10 to 20 years follow-up have demonstrated primary cementless TKA survival of contemporary designs that is comparable with or exceeds that of its cemented counterpart, with some series demonstrating no revisions for aseptic loosening. A higher degree of precision and accuracy in bone preparation and soft tissue balancing seems to be required when utilizing biologically fixed implants. Although originally explored to address the higher demands of the physiologically younger, more active population of patients, cementless technology offers potential benefits in bone conservation, simplifying the performance of the TKA procedure and in increasing operating room efficiency. In addition, theoretical potential reductions in perioperative morbidity and mortality may be realized in association with a shorter duration surgery. Continuing advances in the areas of material science, additive manufacturing, and system design simplification portend a continued positive and expanding role for cementless fixation in both primary and revision TKA in the near and distant future.
The Mobile-bearing TKA: Is There Still a Place?
Authors: Ollivier Matthieu , Parratte Sébastien , Flecher Xavier , Argenson Jean-Noël
Published: February 2018

During the 1980s, fixed-bearing total knee arthroplasty (TKA) became a reliable, reproducible procedure with about 95% implant survival after 10 years. However, implant loosening and polyethylene wear became recognized as long-term causes of late failure. If loosening is related to abnormal strains at the bone-implant interface, polyethylene wear is mainly caused by the lack of congruency during implant motion, and thus surgeons tried to improve TKA’s kinematics by introducing a second degree of freedom in their implants. Mobile-bearing knee replacements are based on a mobile polyethylene insert that articulates with a metallic femoral component and a metallic tibial tray. Those TKA designs have sought to increase congruency without increasing the stresses on the implant fixation. In vitro kinematic studies have shown reduced polyethylene wear in mobile bearings because of increased implant conformity and reduced polyethylene contact. In vivo kinematic analysis tends to confirm that mobile-bearing implants allow more natural knee movement. Despite several prospective, randomized studies having been performed, there is no clinical evidence supporting mobile bearing superiority over fixed-bearing designs. Studies focusing on gait parameters, clinical scores, or implant survival failed to confirm in vitro substantial advantage of mobile-bearing implants. More, recent improvement in polyethylene materials might solve wear issues: the last generation of cross-linked polyethylene, associated with a more morphometric design will probably provide superior implant survivorship and more physiological knee biomechanics.
How Surrogate Decision-Makers for Patients With Chronic Critical Illness Perceive and Carry Out Their Role
Authors: Li Lingsheng , Nelson Judith E. , Hanson Laura C. , Cox Christopher E. , Carson Shannon S. , Chai Emily J. , Keller Kristine L. , Tulsky James A. , Danis Marion
Published: February 2018

Objectives:

Family members commonly make medical decision for patients with chronic critical illness. This study examines how family members approach this decision-making role in real time.

Design:

Qualitative analysis of interviews with family members in the intervention arm of a randomized controlled communication trial.

Settings:

Medical ICUs at four U.S. hospitals.

Participants:

Family members of patients with chronic critical illness (adults mechanically ventilated for ≥ 7 d and expected to remain ventilated and survive for ≥ 72 hr) who participated in the active arm of a communication intervention study.

Interventions:

Family members participated in at least two content-guided, informational, and emotional support meetings led by a palliative care physician and nurse practitioner.

Measurements and Main Results:

Grounded theory was used for qualitative analysis of 66 audio recordings of meetings with 51 family members. Family members perceived their role in four main ways: voice of the patient, advocate for the patient, advocate for others, and advocate for oneself. Their decision-making was characterized by balancing goals, sharing their role, keeping perspective, remembering previous experiences, finding sources of strength, and coping with various burdens.

Conclusions:

Family members take a multifaceted approach as they participate in decision-making. Understanding how surrogates perceive and act in their roles may facilitate shared decision-making among clinicians and families during critical care.
The rationale for a role for diet and nutrition in the prevention and treatment of cancer
Authors: Logan Jean , Bourassa Megan W.
Published: February 2018

There is considerable evidence to support dietary recommendations for prevention of cancer as well as for patients undergoing or recovering from cancer treatment. We consider here implications from human, animal and in-vitro studies of the effects of dietary factors (macronutrients and micronutrients-phytochemicals) on cancer. An important epidemiology study, the China Project found a significant correlation between disease incidence and markers of animal product consumption. Evidence of the role of animal protein in the promotion of cancer also comes from animal studies. Food restriction has been shown in human and animal studies to slow cancer progression. Phytochemicals from whole plant foods are protective against oxidative stress, inhibit cell proliferation, induce cell-cycle arrest, and apoptosis, act as antiangiogenesis factors, and inhibit cyclooxygenase-2, which has been related to metastasis. Some mechanisms that mediate the effect of diet on cancer involve cell signaling through insulin factors and mammalian target of rapamycin, a nutrient sensing complex related to growth, altered gene expression through epigenetics, and the effects of microbial metabolites produced by the gut microbiota that is strongly influenced by dietary factors. The evidence accumulating for many years indicates that diet, what we eat every day, can affect disease. Besides preventing the development of cancer, this could also be harnessed to positively influence treatment outcomes as well as prevent recurrence. As research strategies developed for drug studies are not appropriate, it is important that new methodologies be developed to study these effects.
Pembrolizumab for the Treatment of Advanced Salivary Gland Carcinoma
Authors: Cohen Roger B. , Delord Jean-Pierre , Doi Toshihiko , Piha-Paul Sarina A. , Liu Stephen V. , Gilbert Jill , Algazi Alain P. , Damian Silvia , Hong Ruey-Long , Le Tourneau Christophe , Day Daphne , Varga Andrea , Elez Elena , Wallmark John , Saraf Sanatan , Thanigaimani Pradeep , Cheng Jonathan , Keam Bhumsuk
Published: February 2018

Objectives:

Treatment options for patients with unresectable or metastatic salivary gland carcinoma (SGC) are limited. Safety and efficacy of pembrolizumab for SGC expressing programmed death ligand 1 (PD-L1) were explored.

Materials and Methods:

A cohort of patients with advanced, PD-L1-positive SGC was enrolled in the nonrandomized, multicohort, phase Ib trial of pembrolizumab in patients with PD-L1-positive advanced solid tumors (KEYNOTE-028; NCT02054806). Key inclusion criteria included recurrent or metastatic disease, failure of prior systemic therapy, and PD-L1 expression on ≥1% of tumor or stroma cells (per a prototype immunohistochemistry assay). Patients received pembrolizumab 10 mg/kg every 2 weeks for ≥2 years or until confirmed disease progression or unacceptable toxicity. Primary end point was objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1 by investigator review.

Results:

Twenty-six patients with PD-L1-positive SGC were enrolled and treated; median age was 57 years, 88% were men, and 74% had received prior therapy for recurrent/metastatic disease. Confirmed objective response rate after median follow-up of 20 months was 12% (95% confidence interval, 2%-30%), with 3 patients achieving partial response; there were no complete responses. Median duration of response was 4 months (range, 4 to 21 mo). Treatment-related adverse events occurred in 22 patients (85%), resulting in discontinuation in 2 patients and death in 1 (interstitial lung disease); those occurring in ≥15% of patients were diarrhea, decreased appetite, pruritus, and fatigue.

Conclusions:

Pembrolizumab demonstrated promising antitumor activity and a manageable safety profile in patients with advanced, PD-L1-positive SGC.
Impact of United States Preventive Services Task Force Recommendations on Utilization of Prostate-specific Antigen Screening in Medicare Beneficiaries
Authors: Khairnar Rahul , Mishra Mark V. , Onukwugha Eberechukwu
Published: February 2018

Background:

Previous studies assessing the impact of United States Preventive Services Task Force (USPSTF) recommendations on utilization of prostate-specific antigen (PSA) screening have not investigated longer-term impacts of 2008 recommendations nor have they investigated the impact of 2012 recommendations in the Medicare population. This study aimed to evaluate change in utilization of PSA screening, post-2008 and 2012 USPSTF recommendations, and assessed trends and determinants of receipt of PSA screening in the Medicare population.

Methods:

This retrospective study of male Medicare beneficiaries utilized Medicare Current Beneficiary Survey data and linked administrative claims from 2006 to 2013. Beneficiaries aged ≥65 years, with continuous enrollment in parts A and B for each year they were surveyed were included in the study. Beneficiaries with self-reported/claims-based diagnosis of prostate cancer were excluded. The primary outcome was receipt of PSA screening. Other measures included age groups (65 to 74 and ≥75), time periods (pre-2008/post-2008 and 2012 recommendations), and sociodemographic variables.

Results:

The study cohort consisted of 11,028 beneficiaries, who were predominantly white (87.56%), married (69.25%), and unemployed (84.4%); 52.21% beneficiaries were aged ≥75. Declining utilization trends for PSA screening were observed in men aged ≥75 after 2008 recommendations and in both age groups after 2012 recommendations. The odds of receiving PSA screening declined by 17% in men aged ≥75 after 2008 recommendations and by 29% in men aged ≥65 after 2012 recommendations.

Conclusions:

The 2008 and 2012 USPSTF recommendations against PSA screening were associated with declines in utilization of PSA screening during the study period. USPSTF recommendations play a significant role in affecting utilization patterns of health services.