bluuebunny/crossref_metadata_2025 huggingface dataset:
Prolonged depolarization elicited in Purkinje cell dendrites by climbing fibre impulses in the cat.
Authors: Ekerot C F , Oscarsson O
Published: December 2015

1. Responses evoked in Purkinje cell dendrites by impulses in climbing fibres were studied by recording from the cat cerebellar cortex. Intra‐ and extracellular responses from dendrites of single Purkinje cells were recorded, as well as field responses from the intact cerebellar surface. The intracellular responses were presumably recorded from relatively proximal dendrites. The resting potential usually was 20‐40 mV. The responses consisted of an initial spike‐like component (amplitude 10‐30 mV) followed by a plateau‐like component (amplitude 2‐12 mV) with a duration of about 100 ms. The duration of consecutive responses varied little. 3. The extracellular unitary responses were recorded from more distal dendrites. These responses were negative deflexions consisting of an initial component followed by a plateau‐like component (amplitude 5‐15 mV). The duration of consecutive responses varied widely from about 25 ms to more than 1 s. The negative deflexions are assumed to correspond to dendritic depolarizations. 4. The field responses recorded from the cerebellar surface consisted of a positivity followed by a negativity lasting several hundred milliseconds. The positivity signals the e.p.s.p.s generated by the climbing fibre synapses which do not extend to the most distal dendrites. The negativity presumably signals the plateau‐like dendritic depolarizations which would involve also the most distal dendrites. 5. The nature and significance of the plateau‐like depolarizations evoked by climbing fibre impulses in the purkinje cell dendrites are discussed.
Spatial consequences of bleaching adaptation in cat retinal ganglion cells.
Authors: Bonds A B , Enroth‐Cugell C
Published: December 2015

1. Experiments were conducted to study the effects of localized bleaching on the centre responses of rod‐driven cat retinal ganglion cells. 2. Stimulation as far as 2 degrees from the bleaching site yielded responses which were reduced nearly as much as those generated at the bleaching site. Bleaching in the receptive field middle reduced responsiveness at a site 1 degrees peripheral more than bleaching at that peripheral site itself. 3. The effectiveness of a bleach in reducing centre responsiveness is related to the sensitivity of the region in which the bleach is applied. 4. Response reduction after a 0.2 degree bleach followed the same temporal pattern for concentric test spots of from 0.2 to 1.8 degrees in diameter, implying a substantially uniform spread of adaptation within these bounds. 5. A linear trade‐off between fraction of rhodopsin and area bleached over a range of 8:1 yields the same pattern of response reduction, implying that the non‐linear nature of bleaching adaptation is a property of the adaptation pool rather than independent photoreceptors.
Primary afferent depolarization in the in vitro frog olfactory bulb
Authors: Jahr C. E. , Nicoll R. A.
Published: December 2015

1. Experiments on the frog olfactory bulb have been performed in vitro in order to determine whether primary afferent transmission is modified by presynaptic inhibition.

2. Stimulation of the olfactory nerve resulted in a prolonged depolarization of the olfactory nerve as recorded across a sucrose gap. Unstimulated olfactory nerve fibres adjacent to the stimulated fibres were also depolarized.

3. An excitability increase of the olfactory nerve terminals was found that lasted the entire duration of the olfactory nerve depolarization, indicating that the terminals themselves were depolarized. Both the olfactory nerve depolarization and the excitability increase were blocked by cobalt and manganese ions.

4. Low concentrations of glutamate were found to produce a substantial depolarization of the olfactory nerve. Although gamma‐aminobutyric acid (GABA) also elicited a depolarization of the olfactory nerve, picrotoxin, a GABA antagonist, did not reduce the stimulus‐evoked olfactory nerve depolarization.

5. Recording with potassium‐sensitive electrodes in the olfactory nerve terminal region demonstrated an increase in extracellular potassium with the same rise time and duration as the olfactory nerve depolarization. Cobalt and manganese blocked the potassium increase and the olfactory nerve depolarization without affecting the presynaptic action potential.

6. The focally recorded extracellular current resulting from orthodromic synaptic excitation of the secondary olfactory relay neurones was blocked at short intervals by paired stimulation and decreased for the duration of the olfactory nerve depolarization. This suggests a decreased release of transmitter from the olfactory nerve terminals.

7. The possible role of potassium and/or a neurotransmitter in generating the olfactory nerve depolarization and inhibition is discussed.
Effect of chloride ions on giant miniature end‐plate potentials at the frog neuromuscular junction.
Authors: Molenaar P C , Oen B S , Polak R L
Published: December 2015

1. Frog sartorius muscles were incubated in Ringer solutions with a raised K+ concentration (high K+) and then allowed to recover in medium with a normal K+ concentration. During the recovery period miniature end‐plate potentials (m.e.p.p.s) were recorded with intracellular electrodes. In addition, the acetylcholine (ACh) released from muscles in the presence of high K+ was measured by a mass spectrometric method. 2. Incubation in a high‐K+ medium induced the appearance of giant miniature end‐plate potentials (g.m.e.p.p.s). However, if the Cl‐ of the medium was substituted by propionate, very few g.m.e.p.p.s were observed. This was due to the absence of Cl‐ and not to the presence of propionate. The frequency of g.m.e.p.p.s was also greatly depressed when the Cl‐ concentration was lowered from 120 to 60 mM. 3. The amount of ACh released into a high‐K+ medium was the same, regardless of whether Cl‐ or propionate was the anion. 4. When Cl‐ was replaced by NO3‐ or Br‐, incubation in high‐K+ Ringer solution induced the appearance of g.m.e.p.p.s. However, SO4(2‐), like propionate, was unable to substitute for Cl‐ in this respect. 5. The frequency of g.m.e.p.p.s was correlated with that of m.e.p.p.s during the recovery period. However, when the K+ concentration was raised to 17 mM the frequency of m.e.p.p.s greatly increased, whereas that of the g.m.e.p.p.s did not change significantly. 6. G.m.e.p.p.s disappeared in the presence of curare, but persisted in the presence of tetrodotoxin or in a Ca2+‐lacking medium. However, g.m.e.p.p.s failed to appear when the medium had lacked Ca2+ during the stimulation. 7. It is tentatively concluded that g.m.e.p.p.s are associated with Cl‐‐dependent processes which occur after stimulation of transmitter release, and which are linked with the endocytotic retrieval of presynaptic membrane.
The cardiovascular responses elicited from the posterior cerebellar cortex in the anaesthetized and decerebrate rabbit.
Authors: Bradley D J , Ghelarducci B , Paton J F , Spyer K M
Published: December 2015

1. In this study the posterior cerebellar cortex has been electrically stimulated and changes in heart rate, arterial blood pressure, regional blood flows and renal sympathetic nerve discharge have been recorded in both the anaesthetized and the decerebrate unanaesthetized rabbit. 2. Specifically, lobules VII, VIII, IX and X of the posterior cerebellar vermis were stimulated but the only region which elicited cardiovascular changes was lobule IX (the uvula). The responsive area of the uvula was localized to the medial regions of sublobules a, b and c and was identical in both anaesthetized and decerebrate animals. 3. Under urethane anaesthesia, uvula stimulation evoked a small bradycardia, a fall in arterial pressure, a transient inhibition of renal sympathetic nerve activity, with no change in renal vascular conductance, and an increase in femoral vascular conductance. 4. Stimulation of an identical area in the decerebrate rabbit evoked a marked tachycardia, an increase in blood pressure, maintained increase in renal sympathetic nerve discharge, and decreases in both renal and femoral conductances. 5. The response evoked from the decerebrate rabbit could be reversed by a small dose of anaesthetic to a pattern of response which was essentially identical to that seen in the urethane‐anaesthetized rabbit. 6. This influence of anaesthetics on the pattern of cardiovascular responses that may be elicited from the cerebellar cortex indicates that caution should be exercised when making physiological inferences on the basis of stimulation experiments in anaesthetized preparations. 7. In the light of the cardiovascular changes that may be evoked from the uvula, and recent neuroanatomical and neurophysiological data concerning afferent and efferent connexions of this cerebellar region, we discuss the possibility that the uvula plays a role in the alerting reaction of the rabbit.
Quantal currents evoked by graded intracellular depolarization of crayfish motor axon terminals.
Authors: Atwood H L , Parnas H , Parnas I , Wojtowicz J M
Published: December 2015

1. Quantal transmitter release was examined at nerve terminals of the excitatory motor axon of the crayfish opener muscle. The magnitude of synaptic currents, recorded with macro‐patch electrodes at a nerve terminal, served as a measure of quantal size. Transmitter release was initiated by pulses of depolarizing current applied intracellularly to the axonal terminals after application of tetrodotoxin. Quantal release was altered by a variety of methods and the resulting quantal output and quantal size were measured. 2. Amplitude distributions of quantal events were obtained during experimental manipulations which altered the rate of quantal release by up to 25‐fold. These manipulations consisted of: varying pulse amplitude or pulse duration; facilitating the release by prolonged depolarization; and application of a potassium channel blocker, 4‐aminopyridine. 3. The amplitude of quantal events is impervious to marked changes in presynaptic depolarization and is not affected by experimental procedures which promote accumulation of calcium ions in the terminals. The vesicular mechanism of release, in which transmitter substance is prepackaged in vesicles which individually undergo exocytosis at a release zone, could account for the observed results.
Mapping of early development of electrical activity in the embryonic chick heart using multiple‐site optical recording.
Authors: Hirota A , Kamino K , Komuro H , Sakai T
Published: December 2015

1. Using a multiple‐site optical recording method with a 100‐element photodiode array and a voltage‐sensitive merocyanine‐rhodanine dye, we have been able to monitor, for the first time, spontaneous electrical activity in pre‐fused cardiac primordia in the 6‐ and 7‐somite chick embryos. 2. To study the regional development of spontaneous electrical activity in the early embryonic pre‐contractile chick heart at the later 7‐9‐somite stages, we have also recorded optically action potentials simultaneously from the entire heart, and constructed maps of the early development of electrical activity. 3. The data show that during the 6‐9‐somite stages, the size of the active area gradually increases, and that the development of electrical activity was spatially non‐uniform: two peaks of activity were found in the right and left sides of the cono‐ventricular region at the 7‐8‐somite stages. As development proceeded to the 9‐somite stage, several peak areas of activity appeared. 4. The results are discussed in relation to the spatial pattern of proliferation of electrically active cells in the early phases of cardiogenesis.
A transient calcium‐dependent potassium component of the epileptiform burst after‐hyperpolarization in rat hippocampus.
Authors: Alger B E , Williamson A
Published: December 2015

1. The epileptiform burst potential produced by picrotoxin is a model of the interictal spike potential seen in epilepsy. We have studied the epileptiform burst after‐hyperpolarization (epileptiform burst AHP) using intracellular recording from rat CA1 hippocampal pyramidal cells in the slice preparation. In most experiments burst potentials were induced by electrical stimulation of afferent fibres, but in some experiments bursts that arose spontaneously were also investigated. 2. Previous evidence suggested that the epileptiform burst AHP has two slow K+‐dependent components and that both components would be blocked by phorbol esters that activate protein kinase C. We found that phorbol esters indeed blocked the slow components, but also uncovered a transient hyperpolarizing component of the epileptiform burst AHP. This phorbol‐ester‐insensitive component (the transient AHP) peaked approximately 65 ms after the onset of the stimulus and lasted approximately 150 ms. The transient AHP is K+ dependent since its reversal potential shifted in elevated [K+]o, whereas Cl‐ loading of the cell had no effect on either its development or reversal potential. 3. The transient AHP was either greatly reduced or abolished by 5‐10 mM‐tetraethylammonium (TEA) and by 15‐20 nM‐charybdotoxin (CTX), both of which block a particular Ca2+‐dependent K+ current. Concomitant with the block of the transient AHP was a significant increase in burst duration. The transient AHP was not blocked by up to 1 mM‐4‐aminopyridine (4‐AP), 1 mM‐N'‐2'‐O‐dibutyryl‐adenosine 3':5'‐cyclic monophosphate (dBcAMP) or 50 microM‐carbamylcholine (carbachol), and burst duration was relatively unaffected by these agents. 4. The transient AHP is Ca2+ dependent: (1) it was often associated with the occurrence of a slow, Ca2+‐dependent spike; (2) its amplitude was increased in either elevated [Ca2+] saline or in (3) Bay K 8644 (5‐10 microM), a compound that prolongs the open time of certain Ca2+ channels. 5. We conclude that a Ca2+‐dependent K+ conductance is transiently activated by the epileptiform burst potential. Its distinctive pharmacological profile indicates that it is fundamentally different from the slow Ca2+‐dependent K+ conductance. The Ca2+‐dependent K+ current, IC, may mediate the transient AHP. Our data also suggest that the transient AHP conductance plays an important role in repolarizing the membrane after bursts of action potentials.
Action of antibodies directed against the acetylcholine receptor on channel function at mouse and rat motor end‐plates.
Authors: Dolly J O , Gwilt M , Lacey G , Newsom-Davis J , Vincent A , Whiting P , Wray D W
Published: December 2015

1. The acute effects of antibodies (both polyclonal and monoclonal) raised against the acetylcholine receptor were studied at mouse and rat end‐plates. Isolated muscles were incubated in solutions containing antibody for 2 1/4 to 3 1/2 h. Intracellular microelectrode techniques were then used to record miniature end‐plate potentials (MEPPs) and voltage noise. 2. Most antibody preparations investigated did not reduce MEPP amplitudes as compared with controls. One monoclonal (C7) and one polyclonal (J) preparation irreversibly reduced MEPP amplitudes. Both preparations caused reductions in acetylcholine‐induced depolarization and associated channel opening frequency (from voltage noise analysis). Single‐channel depolarization was not altered by these antibodies. 3. On the basis of these and previous results, four antibody binding regions on the receptor surface were distinguished according to whether channel function and/or alpha‐bungarotoxin binding were affected. Although most antibody preparations did not affect channel function, monoclonal antibody C7 appeared to alter function by acting on the channel itself so as to prevent channel opening.
Flow Visualization of Submerged Steam Jet in Subcooled Water
Authors: Yuan Fang , Zhao Quanbin , Chong Daotong , Chen Weixiong
Published: December 2015

Steam discharged into subcooled water is investigated experimentally to demonstrate the direct contact condensation phenomena in nuclear reactor safety system and underwater propulsion apparatus. The steam jet condenses to various shapes at different thermal hydraulic conditions. A condensation regime diagram is drawn to classify the regime for different flow patterns, among which there are three typical shapes of steam plume characterizing the chugging, condensation oscillation, stable condensation regime (Figure 1). The flow region can be separated into three parts—vapor, water and two-phase regions, and the white patch in the image indicating the two-phase region is a mixture of condensed vapor and subcooled water. Three typical stages of bubble motions—growth (subimage 1 to 6, Figure 2), necking (subimage 7 to 10, Figure 2), and detachment (subimage 11 to 13, Figure 2)—are demonstrated. The bubble diameter reaches the maximum at the necking stage and remains approximately invariant with the connecting neck prolonging for a period. A series of sequent photos exhibits shape transformations at the stable condensation regime, implying that the steam plume grows and shortens periodically due to comprehensive effects of injection, viscosity damping and condensation (Figure 3). The dimensionless penetration length, defined as the ratio of penetration length to nozzle diameter, is in the range of 8.23–11.67 in the Figure 3. The majority of previous literatures present the average dimensionless penetration length which is closely related with time-averaged heat transfer characteristic. However, variations of steam plume are proven to account for pressure oscillation phenomena by the transient visualization investigations, in which the first dominant frequency acquired from the FFT domain graph of pressure signal is consistent with the period of steam plume variations. The second dominant frequency is verified to be caused by oscillations of detached bubbles (subimage 8 and 9, Figure 3) in the research.
Integrated Investigation of Dynamic Drainage Volume and Inflow Performance Relationship (Transient IPR) to Optimize Multistage Fractured Horizontal Wells in Tight/Shale Formations
Authors: Yuan Bin , Ghanbarnezhad Moghanloo Rouzbeh , Shariff Emad
Published: December 2015

This study presents an integrated approach to evaluate the efficiency of fracturing stimulation and predict well production performance. As the pressure disturbance propagates throughout the reservoir during long-time transient flow regimes, it will shape an expanding drainage volume. A macroscopic “compressible tank model (CTM)” using weak (integral) form of mass balance equation is derived to relate dynamic drainage volume (DDV) and average reservoir pressure to production history in extremely shale reservoirs. Fluids and rock compressibility, desorption parameters (for shale or coal gas), and production rates control the speed at which the boundaries advance. After the changes of average reservoir pressure within the expanding drainage volume are obtained, a new empirical inflow performance relationship (transient IPR) correlation is proposed to describe well performance during long transient flow periods in shale reservoirs. This new empirical correlation shows better match performance with field data than that of conventional Vogel-type IPR curves. The integrated approach of both CTM model and transient IPR correlation is used to determine and predict the optimal fracturing spacing and the size of horizontal section for few wells from one of shale oil plays in U.S. The results suggest the existence of optimal fracture spacing and horizontal well length for multistage fractured horizontal wells in shale oil reservoirs. In practice, this paper not only provides an insight in understanding the long transient flow production characteristics of shale reservoirs using concept of expanding drainage volume. Neither methods require comprehensive inputs for the strong form (differential) nor any prior knowledge about the sophisticated shale reservoir features (shape, size, etc.), the ultimate drainage volume, the ultimate recovery, optimal fracture spacing, and the length of horizontal section for each well can also be easily obtained by this new integrated analytical method.
Exergy, Energy, and Gas Flow Analysis of Hydrofractured Shale Gas Extraction
Authors: Lior Noam
Published: December 2015

The objectives of this study are to (a) evaluate the exergy and energy demand for constructing a hydrofractured shale gas well and determine its typical exergy and energy returns on investment (ExROI and EROI), and (b) compute the gas flow and intrinsic exergy analysis in the shale gas matrix and created fractures. An exergy system analysis of construction of a typical U.S. shale gas well, which includes the processes and materials exergies (embodied exergy) for drilling, casing and cementing, and hydrofracturing (“fracking”), was conducted. A gas flow and intrinsic exergy numerical simulation and analysis in a gas-containing hydrofractured shale reservoir with its formed fractures was then performed, resulting in the time- and two-dimensional (2D) space-dependent pressure, velocity, and exergy loss fields in the matrix and fractures. The key results of the system analysis show that the total exergy consumption for constructing the typical hydrofractured shale gas well is 35.8 TJ, 49% of which is used for all the drilling needed for the well and casings and further 48% are used for the hydrofracturing. The embodied exergy of all construction materials is about 9.8% of the total exergy consumption. The ExROI for the typical range of shale gas wells in the U.S. was found to be 7.3–87.8. The embodied energy of manufactured materials is significantly larger than their exergy, so the total energy consumption is about 8% higher than the exergy consumption. The intrinsic exergy analysis showed, as expected, very slow (order of 10−9 m/s) gas flow velocities through the matrix, and consequently very small flow exergy losses. It clearly points to the desirability of exploring fracking methods that increase the number and length of effective fractures, and they increase well productivity with a relatively small flow exergy penalty.
Performance Evaluation of Two Photovoltaic Cell Technologies in Fluctuating Weather Conditions, Using EN50530 Test Procedure
Authors: Premalatha L. , Abd Rahim Nasrudin , Fathi Mohamad
Published: December 2015

Generally, photovoltaic (PV) cell manufacturers provide technical information, at standard test conditions (STCs) and nominal operating cell temperature (NOCT) ratings. However, this information is not sufficient to accurately predict the module operations under dynamic weather. In this study, test is conducted under fluctuating irradiance conditions, provided by EN50530 test procedure, to evaluate the performance of multi crystalline silicon and thin-film PV cells. Particular attention is given to the influence that the level and the slope of irradiance change have on the energy yield of PV technologies. This analysis aimed at revealing the appropriate selection of PV technology for obtaining maximum power under dynamic weather conditions.
An Efficient Dynamic Formulation for Solving Rigid and Flexible Multibody Systems Based on Semirecursive Method and Implicit Integration
Authors: Funes Francisco Javier , de Jalón Javier García
Published: December 2015

This paper presents a method for solving the dynamic equations of multibody systems containing both rigid and flexible bodies. The proposed method uses independent coordinates and projects the dynamic equations on the constraint tangent manifold by means of a velocity transformation matrix. It can be used with a wide variety of integration formulae, considering both fixed and variable stepsizes. Topological semirecursive methods are used to take advantage of the relatively small number of parameters needed. An in depth implementation analysis is performed in order to evaluate the terms involved in the integration process. Numerical and stability issues are also discussed.
Flexible antibacterial Zr-Cu-N thin films resistant to cracking
Authors: Musil Jindřich , Zítek Michal , Fajfrlík Karel , Čerstvý Radomír
Published: December 2015

This study investigates how the Cu concentration in Zr-Cu-N films affects the films' antibacterial capacity and mechanical properties. Zr-Cu-N films were prepared by reactive magnetron sputtering from composed Zr/Cu targets using a dual magnetron in an Ar + N2 mixture. The antibacterial capacity of Zr-Cu-N films was tested on Escherichia coli (E. coli) bacteria. The mechanical properties of Zr-Cu-N films were determined from the load vs. displacement curves measured using a Fisherscope H 100 microhardness tester. The antibacterial capacity was modulated by the amount of Cu added to the Zr-Cu-N film. The mechanical properties were varied based on the energy Ei delivered to the growing film by bombarding ions. It was found that it is possible to form Zr-Cu-N films with Cu concentrations ≥10 at. % that simultaneously exhibit (1) 100% killing efficiency Ek for E. coli bacteria on their surfaces, and (2) (1) high hardness H of about 25 GPa, (2) high ratio H/E* ≥ 0.1, (3) high elastic recovery We ≥ 60% and (4) compressive macrostress (σ < 0). The Zr-Cu-N films with these parameters are flexible/antibacterial films that exhibit enhanced resistance to cracking. This enhanced resistance was tested by (1) bending the Mo and Ti strip coated by sputtered Zr-Cu-N films (bending test) and (2) loading the surface of the Zr-Cu-N sputtered on a Si substrate by a diamond indenter at high loads up to 1 N (indentation test). Physical, mechanical, and antibacterial properties of Zr-Cu-N films are described in detail. In summary, it can be concluded that Zr-Cu-N is a promising new material for creating flexible antibacterial coatings on contact surfaces.
Contribution of Physical Interactions to Signaling Specificity between a Diguanylate Cyclase and Its Effector
Authors: Dahlstrom Kurt M. , Giglio Krista M. , Collins Alan J. , Sondermann Holger , O’Toole George A.
Published: December 2015

Cyclic diguanylate (c-di-GMP) is a bacterial second messenger that controls multiple cellular processes. c-di-GMP networks have up to dozens of diguanylate cyclases (DGCs) that synthesize c-di-GMP along with many c-di-GMP-responsive target proteins that can bind and respond to this signal. For such networks to have order, a mechanism(s) likely exists that allow DGCs to specifically signal their targets, and it has been suggested that physical interactions might provide such specificity. Our results show a DGC from
Pseudomonas fluorescens
physically interacting with its target protein at a conserved interface, and this interface can be predictive of DGC-target protein interactions. Furthermore, we demonstrate that physical interaction is necessary for the DGC to maximally signal its target. If such “local signaling” is a theme for even a fraction of the DGCs used by bacteria, it becomes possible to posit a model whereby physical interaction allows a DGC to directly signal its target protein, which in turn may help curtail undesired cross talk with other members of the network.

IMPORTANCE
An important question in microbiology is how bacteria make decisions using a signaling network made up of proteins that make, break, and bind the second messenger c-di-GMP, which is responsible for controlling many cellular behaviors. Previous work has shown that a given DGC enzyme will signal for specific cellular outputs, despite making the same diffusible molecule as its sibling DGCs in the unpartitioned space of the bacterial cell. Understanding how one DGC differentiates its output from the dozens of other such enzymes in the cell is synonymous with understanding a large component of the bacterial decision-making machinery. We present evidence for a helix on a DGC used to physically associate with its target protein, which is necessary to achieve maximal signaling.
Haemophilia A in a major trauma patient
Authors: Reinke Charlotte , Spodeck Agnes , Schildhauer Thomas A , Swol Justyna
Published: December 2015

Haemophilia A is a coagulopathy with an absence or functional deficiency of coagulation factor VIII. The disease can be subdivided into a congenital form (incidence 1:10 000–1:20 000) and an acquired form (incidence 1:1 000 000). Both forms present an increased risk of bleeding even in low-impact trauma in severe cases of haemophilia A. The course of a man with haemorrhagic shock after a fall from a height of more than 3 m is described. After the secondary survey in the intensive care unit, several interventions (laparotomy, mass transfusion) were performed to stop the bleeding. A history of haemophilia was belatedly reported by relatives. The activity of factor VIII was determined, and substitution was initiated. No recurrent signs of bleeding occurred. The patient survived in good condition and presented for follow-up 3 years later with no disabilities.
Serum sickness-like reaction after influenza vaccination
Authors: Chiong Fabian Joon Kiong , Loewenthal Mark , Boyle Michael , Attia John
Published: December 2015

Serum sickness (SS) and SS-like reaction (SSLR) are rare immune complex-mediated hypersensitivity illnesses characterised by key features of fever, rash, polyarthralgia or polyarthritis. They are self-limiting with an excellent prognosis, settling as the antigen is cleared. We describe a 30-year-old man who presented with fever, rash, polyarthralgia and subcutaneous soft tissue swelling in his hands and feet at day 5 after influenza vaccination. A thorough investigation for infective and autoimmune causes for the presenting symptoms was negative. Given the temporal relationship between the symptoms and influenza vaccination, clinical evidence and biological plausibility of influenza vaccination causing SSLR, a clinical diagnosis of SSLR was made. The patient was treated with anti-histamines, non-steroidal anti-inflammatories and glucocorticoids with gradual resolution of symptoms over 5 weeks.
Lung carcinoma presenting as a solitary, painless frontal bone lump
Authors: García Carretero Rafael , Sanchez-Redondo Jorge , Barrio-Alonso Maria-Jesus , Lopez-Marti Maria-Pilar
Published: December 2015

A 50-year-old patient, a smoker, was admitted to the hospital, with a solitary scalp lump. Subcutaneous lumps of the scalp are common but usually benign; however, the painless lump in our patient turned out to be a malignant osteolytic lesion of the skull. Frontal bone was involved, and the disease had spread to the dura. Neuroimaging showed osteolytic lesions involving the axial skeleton, skull and several vertebrae. MRI showed the involvement of the second cervical vertebra, which prompted us to start treatment with dexamethasone. Since the spinal cord was not involved, Oncologists decided not to start radiotherapy treatment until we had reached the final diagnosis. A frontal bone biopsy confirmed the diagnosis of lung carcinoma. Chest X-ray did not identify the pulmonary nodule, but CT scan revealed a 1 cm peripheral, spiculated, pulmonary nodule within a pathological parenchyma (severe diffuse pulmonary emphysema).
Is hypercapnia associated with poor prognosis in chronic obstructive pulmonary disease? A long-term follow-up cohort study
Authors: Yang Hui , Xiang Pingchao , Zhang Erming , Guo Weian , Shi Yanwei , Zhang Shuo , Tong Zhaohui
Published: December 2015

Objectives

To assess whether hypercapnia may predict the prognosis in chronic obstructive pulmonary disease (COPD).

Design

Prospective cohort study comparing the survival of patients with COPD and normocapnia to those with chronic hypercapnia.

Setting

Patients with consecutive COPD were enrolled between 1 May 1993 and 31 October 2006 at two medical centres. Follow-up was censored on 31 October 2011.

Participants

A total of 275 patients with stable COPD and aged 40–85 years were enrolled. Diagnosis of hypercapnia was confirmed by blood gas analysis. Patients with near-terminal illness or comorbidities that affect PaCO2(obstructive sleep apnoea, obesity-related hypoventilation, or neuromuscular disease) were excluded. The outcome of 98 patients with normocapnia and 177 with chronic hypercapnia was analysed.

Outcome measures

Overall survival.

Results

Median survival was longer in patients with normocapnia than in those with hypercapnia (6.5 vs 5.0 years, p=0.016). Multivariate COX regression analysis indicated that age (HR=1.043, 95% CI 1.012 to 1.076), Charlson Index, which is a measure of comorbidity (HR=1.172, 95% CI 1.067 to 1.288), use of medication (HR=0.565, 95% CI 0.379 to 0.842), body mass index (BMI) (HR=0.922, 95% CI 0.883 to 0.963), PaCO2(HR=1.026, 95% CI 1.011 to 1.042), Cor pulmonale (HR=2.164, 95% CI 1.557 to 3.006), non-invasive positive-pressure ventilation (NPPV) (HR=0.615, 95% CI 0.429 to 0.881) and per cent of forced expiratory volume in 1 s (FEV1%) (HR=0.979, 95% CI 0.967 to 0.991), were independent risk factors for mortality.

Conclusions

Increased age, Charlson Index, chronic hypercapnia and Cor pulmonale, and decreased FEV1%, use of medication, BMI and NPPV, were associated with a poor prognosis in patients with COPD.
Size-related habitat use in juvenile Atlantic salmon: the importance of intercohort competition
Authors: Höjesjö Johan , Kaspersson Rasmus , Armstrong John D.
Published: December 2015

In stream-living salmonids, an underlying mechanism for the critical period after emergence has generally been assumed to be size-dependent swimming capacity constraining fry (age-0) to low-velocity habitats with reduced food availability and intense competition. A further plausible mechanism is that intercohort habitat exclusion confines fry to marginal habitats. This possibility was tested using a seminatural stream with 16 test arenas, each comprising one high-velocity, deep habitat and one low-velocity, shallow habitat. We observed groups of newly emerged Atlantic salmon (Salmo salar) fry, either alone or in sympatry with one or two age-1 salmon. Salmon fry used high-velocity areas (42.2 ± 0.4 cm·s−1) most extensively in the absence of intercohort competition, where they obtained more food than in low-velocity areas (3.3 ± 0.3 cm·s−1), even though foraging efficiency was lower (though not significantly so). In sympatry with older cohorts, fry increased their use of the low-velocity habitat, with a reduced foraging activity, suggesting that strong older cohorts in natural populations may have the potential to influence the strength of the recruiting cohort by negative density dependence due to interference competition for habitat.
Phenylalanine transfer across the isolated perfused human placenta: an experimental and modeling investigation
Authors: Lofthouse E. M. , Perazzolo S. , Brooks S. , Crocker I. P. , Glazier J. D. , Johnstone E. D. , Panitchob N. , Sibley C. P. , Widdows K. L. , Sengers B. G. , Lewis R. M.
Published: December 2015

Membrane transporters are considered essential for placental amino acid transfer, but the contribution of other factors, such as blood flow and metabolism, is poorly defined. In this study we combine experimental and modeling approaches to understand the determinants of [14C]phenylalanine transfer across the isolated perfused human placenta. Transfer of [14C]phenylalanine across the isolated perfused human placenta was determined at different maternal and fetal flow rates. Maternal flow rate was set at 10, 14, and 18 ml/min for 1 h each. At each maternal flow rate, fetal flow rates were set at 3, 6, and 9 ml/min for 20 min each. Appearance of [14C]phenylalanine was measured in the maternal and fetal venous exudates. Computational modeling of phenylalanine transfer was undertaken to allow comparison of the experimental data with predicted phenylalanine uptake and transfer under different initial assumptions. Placental uptake (mol/min) of [14C]phenylalanine increased with maternal, but not fetal, flow. Delivery (mol/min) of [14C]phenylalanine to the fetal circulation was not associated with fetal or maternal flow. The absence of a relationship between placental phenylalanine uptake and net flux of phenylalanine to the fetal circulation suggests that factors other than flow or transporter-mediated uptake are important determinants of phenylalanine transfer. These observations could be explained by tight regulation of free amino acid levels within the placenta or properties of the facilitated transporters mediating phenylalanine transport. We suggest that amino acid metabolism, primarily incorporation into protein, is controlling free amino acid levels and, thus, placental transfer.
Endogenous VMH amylin signaling is required for full leptin signaling and protection from diet-induced obesity
Authors: Dunn-Meynell Ambrose A. , Le Foll Christelle , Johnson Miranda D. , Lutz Thomas A. , Hayes Matthew R. , Levin Barry E.
Published: December 2015

Amylin enhances arcuate (ARC) and ventromedial (VMN) hypothalamic nuclei leptin signaling and synergistically reduces food intake and body weight in selectively bred diet-induced obese (DIO) rats. Since DIO 125I-amylin dorsomedial nucleus-dorsomedial VMN binding was reduced, we postulated that this contributed to DIO ventromedial hypothalamus (VMH) leptin resistance, and that impairing VMH (ARC + VMN) calcitonin receptor (CTR)-mediated signaling by injecting adeno-associated virus (AAV) expressing a short hairpin portion of the CTR mRNA would predispose diet-resistant (DR) rats to obesity on high-fat (45%) diet (HFD). Depleting VMH CTR by 80–90% in 4-wk-old male DR rats reduced their ARC and VMN 125I-labeled leptin binding by 57 and 51%, respectively, and VMN leptin-induced phospho-signal transducer and activator of transcription 3-positive neurons by 59% vs. AAV control rats. After 6 wk on chow, VMH CTR-depleted DR rats ate and gained the equivalent amount of food and weight but had 18% heavier fat pads (relative to carcass weight), 144% higher leptin levels, and were insulin resistant compared with control AAV DR rats. After 6 wk more on HFD, VMH CTR-depleted DR rats ate the same amount but gained 28% more weight, had 60% more carcass fat, 254% higher leptin levels, and 132% higher insulin areas under the curve during an oral glucose tolerance test than control DR rats. Therefore, impairing endogenous VMH CTR-mediated signaling reduced leptin signaling and caused DR rats to become more obese and insulin resistant, both on chow and HFD. These results suggest that endogenous VMH amylin signaling is required for full leptin signaling and protection from HFD-induced obesity.
Nexus between Artisanal and Small-Scale Gold Mining and Livelihood in Prestea Mining Region, Ghana
Authors: Arthur Francis , Agyemang-Duah Williams , Gyasi Razak Mohammed , Yeboah Joseph Yaw , Otieku Evans
Published: December 2015

Drawing on the DFID’s sustainable livelihood framework, this paper explores the nexus between artisanal and small-scale mining (ASM) and livelihood in Prestea mining region, Ghana. A cross-sectional mixed method survey involving simple random and purposively sampled participants (N=151) was carried out. The results suggest both positive and negative relationships between ASM and livelihoods of the people. The study found various livelihood assets associated with ASM and how critical assets are adversely affected by ASM activities. Limited employment opportunities in rural areas (82%), economic hardships/poverty situations of people (59%), and “quick” income earnings from ASM (90%) were the major factors that influenced people to combine and use their personal assets to enable them to engage in ASM. ASM contributes to the livelihood enhancement through income generation, increased well-being and asset acquisition (50.7%), reduced vulnerabilities (31.1%), and empowerment of people (19.2%) to establish other economic activities. However, the small-scale miners and farmers as well as farmlands, forest, and water resources are most vulnerable to adverse effects of ASM activities. Accidents of various degrees, diseases, and death were the shocks in ASM. Regarding the massive impact of ASM on employment creation and poverty reduction in rural communities, it is recommended that stakeholders recast Ghana’s mineral policy to ensure concurrent environmental sustainability and socioeconomic development.
It's Totally Tubular…Riding The New Wave of Ovarian Cancer Research
Authors: Perets Ruth , Drapkin Ronny
Published: December 2015

Hereditary breast and ovarian cancer syndrome carries significant mortality for young women if effective preventive and screening measures are not taken. Preventive salpingo-oophorectomy is currently the only method known to reduce the risk of ovarian cancer-related death. Histopathological analyses of these surgical specimens indicate that a high proportion of ovarian cancers in women at high risk and in the general population arise from the fallopian tube. This paradigm shift concerning the cell of origin for the most common subtype of ovarian cancer, high-grade serous carcinoma, has sparked a major effort within the research community to develop new and robust model systems to study the fallopian tube epithelium as the cell of origin of “ovarian” cancer. In this review, evidence supporting the fallopian tube as the origin of ovarian cancer is presented as are novel experimental model systems for studying the fallopian tube epithelium in high-risk women as well as in the general population. This review also addresses the clinical implications of the newly proposed cell of origin, the clinical questions that arise, and novel strategies for ovarian cancer prevention. Cancer Res; 76(1); 10–17. ©2015 AACR.
Assessing the Cumulative Contribution of New and Established Common Genetic Risk Factors to Early-Onset Prostate Cancer
Authors: Lange Ethan M. , Ribado Jessica V. , Zuhlke Kimberly A. , Johnson Anna M. , Keele Gregory R. , Li Jin , Wang Yunfei , Duan Qing , Li Ge , Gao Zhengrong , Li Yun , Xu Jianfeng , Zheng S. Lilly , Cooney Kathleen A.
Published: December 2015

Background: We assessed the evidence for association between 23 recently reported prostate cancer variants and early-onset prostate cancer and the aggregate value of 63 prostate cancer variants for predicting early-onset disease using 931 unrelated men diagnosed with prostate cancer prior to age 56 years and 1,126 male controls.

Methods: Logistic regression models were used to test the evidence for association between the 23 new variants and early-onset prostate cancer. Weighted and unweighted sums of total risk alleles across these 23 variants and 40 established variants were constructed. Weights were based on previously reported effect size estimates. Receiver operating characteristic curves and forest plots, using defined cut-points, were constructed to assess the predictive value of the burden of risk alleles on early-onset disease.

Results: Ten of the 23 new variants demonstrated evidence (P < 0.05) for association with early-onset prostate cancer, including four that were significant after multiple test correction. The aggregate burden of risk alleles across the 63 variants was predictive of early-onset prostate cancer (AUC = 0.71 using weighted sums), especially in men with a high burden of total risk alleles.

Conclusions: A high burden of risk alleles is strongly associated with early-onset prostate cancer.

Impact: Our results provide the first formal replication for several of these 23 new variants and demonstrate that a high burden of common-variant risk alleles is a major risk factor for early-onset prostate cancer. Cancer Epidemiol Biomarkers Prev; 25(5); 766–72. ©2015 AACR.
Exploring Visual Selective Attention towards Novel Stimuli in Alzheimer's Disease Patients
Authors: Chau Sarah A. , Herrmann Nathan , Eizenman Moshe , Chung Jonathan , Lanctôt Krista L.
Published: December 2015

Background: Alzheimer's disease (AD) is associated with selective attention impairments, which could contribute to cognitive and functional deficits. Selective attention can be explored through examination of novelty preference. Aims: In this study, we quantified novelty preference in AD patients by measuring visual scanning behaviour using an eye tracking paradigm. Methods: Mild-to-moderate AD patients and elderly controls viewed slides containing novel and repeated images simultaneously. The outcome measure was time spent on specific images, with novelty preference defined by greater relative fixation time (RFT) on novel versus repeated images. Cognitive status (Standardized Mini-Mental State Examination, SMMSE) and attention (Digit Span, DS) were also measured. Results: AD patients (age 79.2 ± 6.7 years, SMMSE 22.2 ± 4.0, n = 41) and controls (age 76.2 ± 6.4 years, SMMSE 28.1 ± 2.0, n = 24) were similar in age, education and sex. Compared with controls, AD patients had lower RFT on novel than on repeated images (F1,63 = 11.18, p = 0.001). Further, reduced RFT was associated with lower scores on SMMSE (r63 = 0.288, p = 0.020) and DS (r63 = 0.269, p = 0.030). Within individuals, novelty preference was detected in 92.3% of patients and in 100% of controls. Conclusion: These findings suggest that novelty preference, measured by visual scanning behaviour, can differentiate cognitively healthy and impaired people and may offer a nonverbal, less cognitively demanding method of assessing selective attention.
Determinants and Prognostic Significance of Hematoma Sedimentation Levels in Acute Intracerebral Hemorrhage
Authors: Sato Shoichiro , Delcourt Candice , Zhang Shihong , Arima Hisatomi , Heeley Emma , Zheng Danni , Al-Shahi Salman Rustam , Stapf Christian , Tzourio Christophe , Robinson Thompson , Lindley Richard I. , Chalmers John , Anderson Craig S. ,   for the INTERACT2 Investigators
Published: December 2015

Background: This study aimed at identifying the determinants and prognostic significance of a sedimentation level (fluid-blood level) in the hematoma among patients with acute intracerebral hemorrhage (ICH) who participated in the main Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2). Methods: Post-hoc analysis of the INTERACT2 dataset, a randomized controlled trial of patients with acute ICH with elevated systolic blood pressure (SBP), randomly assigned to intensive (target SBP <140 mm Hg) or guideline-based (<180 mm Hg) BP management. Patients with a sedimentation level at baseline assessment on CT, and modified Rankin Scale score at 90-day, were included in these analyses. Factors associated with a sedimentation level and its significance in relation to 90-day clinical outcomes were assessed in univariable and multivariable logistic regression models. Results: Of 2,065 participants, 19 (1%) had sedimentation level on baseline CT, which was independently associated with warfarin use (p = 0.006) and lobar ICH (p = 0.025). Sedimentation level was also associated with death or major disability at 90-day in both crude (84 vs. 53%; p = 0.014) and multivariable analyses adjusted for age, gender, Chinese region, warfarin use, baseline National Institutes of Health Stroke Scale score, onset to CT time, volume and location of ICH, intraventricular extension, and randomized intensive BP lowering (OR 3.94, 95% CI 1.01-15.37; p = 0.049). Conclusions: The presence of hematoma sedimentation level on baseline CT is associated with warfarin use and lobar location of ICH, and predicts a worse outcome. Although uncommon, sedimentation level is an easily detectable prognostic factor in acute ICH.