bluuebunny/crossref_metadata_2025_split huggingface dataset:
Promising Trends in Access to Medicines
Authors: Richard Gold E. , Morin Jean‐Frédéric 
Published: May 2012

AbstractIt is a vast understatement to say that the problem of access to medicines in developing countries is complex. Access is limited by a range of factors including inability to pay, a lack of infrastructure, and corruption in some countries. Surrounding and exacerbating these structural and technological problems is the layer of legal rights created by patents and their licensing that complicate and render more expensive the preparation and delivery of needed medicines, particularly those that need to be adapted to the social, health and cultural environment of developing countries. This article provides a survey of innovative strategies that aim at maximizing the potential of patents to facilitate the development and delivery of medicines against diseases, the burden of which falls principally on developing country populations. To understand the context in which these strategies are being proposed and implemented, the article reviews the battles over access to medicines beginning in the late 1980s. It then surveys some of the principal suggestions put forward to better direct innovation systems in addressing the critical health needs of the world’s majority including advance market commitments, patent buy‐outs, prize funds, public–private partnerships and patent pools.
Global Inequality: From Class to Location, from Proletarians to Migrants
Authors: Milanovic Branko 
Published: May 2012

AbstractInequality between world citizens in the mid‐19th century was such that at least a half of it could be explained by income differences between workers and capital owners in individual countries. Real income of workers in most countries was similar and low. This was the basis on which Marxism built its universal appeal. More than 150 years later, in the early 21st century, the situation has changed fundamentally: more than 80 per cent of global income differences is due to large gaps in mean incomes between countries, and unskilled workers′ wages in rich and poor countries often differ by a factor of 10 to 1. This is the basis on which a new global political issue of migration has emerged because income differences between countries make individual gains from migration large. The key coming issue will be how to deal with this new challenge while acknowledging that migration is probably the most powerful tool for reducing global poverty and inequality.Policy Implications
Immigration pressure is intimately related to high income gaps that exist between countries today.
Aid and immigration are complementary tools to deal with global poverty.
If recipient countries have trouble dealing with current migration flows, they should realize that the alternative is to help the growth of countries where most migrants come from. Aid is then seen to be also in rich countries’ own interest.
Such policies require a multilateral approach because of free rider problems.
The effect of line‐up administrator blindness on the recording of eyewitness identification decisions
Authors: Rodriguez Dario N. , Berry Melissa A. 
Published: May 2012

Purpose. Line‐up administrators’ expectations have been shown to influence eyewitnesses’ identification decisions. Expectations may also influence administrators’ willingness to record witnesses’ decisions as positive identifications.Methods. Single‐ and double‐blind participant administrators presented a line‐up to a confederate witness, who identified either the suspect or a filler.Results. A hierarchical log‐linear analysis revealed an interaction effect of blindness and witness choice on participants’ recording of the identification: Single‐blind administrators were more likely to record the confederate's choice as a positive identification when the witness chose the suspect (vs. a filler), whereas double‐blind administrators’ records were not influenced by the witness's choice. An interaction between blindness and witness choice also emerged for participant administrators’ witness evaluations. Single‐blind administrators rated confederates who chose a filler as significantly less credible than those who chose a suspect; double‐blind administrators’ ratings were consistent across photo selection.Conclusions. Blindness influenced line‐up administrators’ record of line‐up outcomes. These results add to the growing body of research supporting the use of double‐blind line‐up administration.
Influence of menstrual cycle phase on muscle metaboreflex control of cardiac baroreflex sensitivity, heart rate and blood pressure in humans
Authors: Hartwich Doreen , Aldred Sarah , Fisher James P. 
Published: May 2012

New Findings
What is the central question of this study?Oestrogen has been reported to modify exercise‐induced autonomic responses and to impact on exercising skeletal muscle blood flow. Together, these oestrogenic influences might attenuate metabolite accumulation and muscle metaboreflex activation during exercise. Moreover, in dogs and in humans, the muscle metaboreflex has been reported to decrease cardiac baroreflex sensitivity during dynamic exercise.
What is the main finding and its importance?Endogenous fluctuations in oestrogen between the early and late follicular phases of the menstrual cycle in healthy women, do not modify either the increase in heart rate and blood pressure or the reduction in spontaneous cardiac baroreflex sensitivity evoked by muscle metaboreflex activation.
We sought to determine whether menstrual cycle phase influences muscle metaboreflex control of spontaneous cardiac baroreflex sensitivity (cBRS), blood pressure (BP) and heart rate (HR). Twenty‐three young women not taking oral contraceptives were studied during the early (EF; low oestrogen, low progesterone) and late follicular menstrual phases (LF; high oestrogen, low progesterone). Protocol 1 consisted of leg cycling at low (21 ± 2 W) and moderate workloads (71 ± 3 W) in free‐flow conditions and with partial flow restriction (bilateral thigh‐cuff inflation at 100 mmHg) to activate the muscle metaboreflex. Protocol 2 consisted of rhythmic hand‐grip exercise with incremental upper arm‐cuff inflation (0, 80, 100 and 120 mmHg) to elicit graded metaboreflex activation. Both protocols were followed by post‐exercise ischaemia. Leg cycling decreased cBRS (EF, 20 ± 5, 6 ± 1 and 1 ± 0.1 ms mmHg−1; and LF, 19 ± 3, 6 ± 0.4, 1 ± 0.1 ms mmHg−1 during rest, low‐ and moderate‐intensity leg cycling, respectively) and increased HR in an intensity‐dependent manner, while BP remained unchanged. Partial flow restriction during leg cycling decreased cBRS, and increased HR and BP. During post‐exercise ischaemia, HR and BP remained elevated, while cBRS remained suppressed (EF, 4.2 ± 0.6 ms mmHg−1; and LF, 4.7 ± 0.5 ms mmHg−1; P < 0.05 versus rest). Cardiac baroreflex sensitivity was unchanged during hand‐grip with and without partial flow restriction and post‐exercise ischaemia. No differences in cBRS, HR or BP responses were observed between EF and LF at any time during either protocol. These data indicate that endogenous fluctuations in oestrogen between the EF and LF phases of the menstrual cycle do not influence muscle metaboreflex control of cBRS, BP or HR in young women.
A‐type K+ channels encoded by Kv4.2, Kv4.3 and Kv1.4 differentially regulate intrinsic excitability of cortical pyramidal neurons
Authors: Carrasquillo Yarimar , Burkhalter Andreas , Nerbonne Jeanne M. 
Published: May 2012

Key points
A‐type K+ currents, IA, are key determinants of neuronal excitability. Previous studies suggest critical roles for voltage‐gated K+ (Kv) channel pore‐forming (α) subunits of the Kv4 subfamily in the generation of neuronal IA channels.
The experiments here examined directly the functional roles of Kv4.2, Kv4.3 and Kv1.4 in the regulation of the intrinsic excitability and the firing properties of mature cortical pyramidal (CP) neurons.
The results demonstrate roles for Kv4.2, Kv4.3 and Kv1.4 in the generation of IA channels and show that Kv4.2‐, Kv4.3‐ and Kv1.4‐encoded IA channels play distinct roles in regulating the intrinsic excitability and the firing properties of CP neurons.
These findings demonstrate previously unappreciated molecular and functional diversity of IA in central neurons, insights that will contribute importantly to future studies focused on determining the mechanisms underlying the alterations in neuronal excitability in epilepsy and other neurological disorders.
Abstract  Rapidly activating and rapidly inactivating voltage‐gated A‐type K+ currents, IA, are key determinants of neuronal excitability and several studies suggest a critical role for the Kv4.2 pore‐forming α subunit in the generation of IA channels in hippocampal and cortical pyramidal neurons. The experiments here demonstrate that Kv4.2, Kv4.3 and Kv1.4 all contribute to the generation of IA channels in mature cortical pyramidal (CP) neurons and that Kv4.2‐, Kv4.3‐ and Kv1.4‐encoded IA channels play distinct roles in regulating the intrinsic excitability and the firing properties of mature CP neurons. In vivo loss of Kv4.2, for example, alters the input resistances, current thresholds for action potential generation and action potential repolarization of mature CP neurons. Elimination of Kv4.3 also prolongs action potential duration, whereas the input resistances and the current thresholds for action potential generation in Kv4.3−/− and WT CP neurons are indistinguishable. In addition, although increased repetitive firing was observed in both Kv4.2−/− and Kv4.3−/− CP neurons, the increases in Kv4.2−/− CP neurons were observed in response to small, but not large, amplitude depolarizing current injections, whereas firing rates were higher in Kv4.3−/− CP neurons only with large amplitude current injections. In vivo loss of Kv1.4, in contrast, had minimal effects on the intrinsic excitability and the firing properties of mature CP neurons. Comparison of the effects of pharmacological blockade of Kv4‐encoded currents in Kv1.4−/− and WT CP neurons, however, revealed that Kv1.4‐encoded IA channels do contribute to controlling resting membrane potentials, the regulation of current thresholds for action potential generation and repetitive firing rates in mature CP neurons.
The human carotid body transcriptome with focus on oxygen sensing and inflammation – a comparative analysis
Authors: Mkrtchian Souren , Kåhlin Jessica , Ebberyd Anette , Gonzalez Constancio , Sanchez Diego , Balbir Alexander , Kostuk Eric W , Shirahata Machiko , Fagerlund Malin Jonsson , Eriksson Lars I 
Published: May 2012

Key points
The carotid body (CB) is the key oxygen sensor and governs the ventilatory response to hypoxia.
CB oxygen sensing and signalling gene expression is well described in animals whereas human data are absent.
Here we have characterized the human CB global gene expression in comparison with functionally related tissues and mouse CB gene expression.
We show that the human CB expresses oxygen sensing genes in common with mice but also differs on key genes such as certain K+ channels. There is moreover increased expression of inflammatory response genes in human and mouse CBs in comparison with related tissues.
The study establishes similarities but also important differences between animal and human CB gene expression profiles and provides a platform for future functional studies on human CBs.
Abstract  The carotid body (CB) is the key oxygen sensing organ. While the expression of CB specific genes is relatively well studied in animals, corresponding data for the human CB are missing. In this study we used five surgically removed human CBs to characterize the CB transcriptome with microarray and PCR analyses, and compared the results with mice data. In silico approaches demonstrated a unique gene expression profile of the human and mouse CB transcriptomes and an unexpected upregulation of both human and mouse CB genes involved in the inflammatory response compared to brain and adrenal gland data. Human CBs express most of the genes previously proposed to be involved in oxygen sensing and signalling based on animal studies, including NOX2, AMPK, CSE and oxygen sensitive K+ channels. In the TASK subfamily of K+ channels, TASK‐1 is expressed in human CBs, while TASK‐3 and TASK‐5 are absent, although we demonstrated both TASK‐1 and TASK‐3 in one of the mouse reference strains. Maxi‐K was expressed exclusively as the spliced variant ZERO in the human CB. In summary, the human CB transcriptome shares important features with the mouse CB, but also differs significantly in the expression of a number of CB chemosensory genes. This study provides key information for future functional investigations on the human carotid body.
Acute and chronic effects of carotid body denervation on ventilation and chemoreflexes in three rat strains
Authors: Mouradian Jr Gary C. , Forster Hubert V. , Hodges Matthew R. 
Published: May 2012

Key points
Carbon dioxide (CO2) provides a major chemical stimulus to breathe, primarily through the activity of CO2/pH sensors called chemoreceptors in the brainstem and in the carotid body.
Carotid body denervation (CBD) causes hypoventilation at rest and reduces ventilatory sensitivity to CO2 in multiple mammalian species, suggesting an important role of the carotid bodies in determining levels of ventilation relative to the CO2 drive to breathe.
CBD in three strains of adult rats with large inherent differences in CO2 sensitivity causes hypoventilation at rest but has no effect on CO2 sensitivity.
These data from rats reinforce the concept that the carotid bodies provide a tonic facilitatory drive to breathe, but differ from other species suggesting a minimal contribution of the carotid bodies to CO2 sensitivity in rats.
Abstract  Brown Norway (BN) rats have a relatively specific deficit in CO2 sensitivity. This deficit could be due to an abnormally weak carotid body contribution to CO2 sensitivity. Accordingly, we tested the hypothesis that CBD would have less of an effect on eupnoeic breathing and CO2 sensitivity in the BN rats compared to other rat strains. We measured ventilation and blood gases at rest (eupnoea) and during hypoxia (= 0.12) or hypercapnia (= 0.07) before and up to 23 days after bilateral or Sham CBD in BN, Sprague–Dawley (SD) and Dahl Salt‐Sensitive (SS) rats. In all three rat strains, CBD elicited eupnoeic hypoventilation (Δ+8.7–11.0 mmHg) 1–2 days post‐CBD (P < 0.05), and attenuated ventilatory responses to hypoxia (P < 0.05) and venous sodium cyanide (NaCN; P < 0.05), while sham CBD had no effect on resting breathing, blood gases or chemoreflexes (P > 0.05). In contrast, CBD had no effect on CO2 sensitivity (Δ/Δ) in all strains (P > 0.05). Eupnoeic returned to pre‐CBD values within 15–23 days post‐CBD. Thus, the effects of CBD in rats (1) further support an important role for the carotid bodies in eupnoeic blood gas regulation, (2) suggest that the carotid bodies are not a major determinant of CO2 sensitivity in rats, and (3) may not support the concept of an interaction among the peripheral and central chemoreceptors in rats.
Validation of a virtual source model for Monte Carlo dose calculations of a flattening filter free linac
Authors: Cashmore Jason , Golubev Sergey , Dumont Jose Luis , Sikora Marcin , Alber Markus , Ramtohul Mark 
Published: May 2012

Purpose:A linac delivering intensity‐modulated radiotherapy (IMRT) can benefit from a flattening filter free (FFF) design which offers higher dose rates and reduced accelerator head scatter than for conventional (flattened) delivery. This reduction in scatter simplifies beam modeling, and combining a Monte Carlo dose engine with a FFF accelerator could potentially increase dose calculation accuracy. The objective of this work was to model a FFF machine using an adapted version of a previously published virtual source model (VSM) for Monte Carlo calculations and to verify its accuracy.Methods:An Elekta Synergy linear accelerator operating at 6 MV has been modified to enable irradiation both with and without the flattening filter (FF). The VSM has been incorporated into a commercially available treatment planning system (Monaco™ v 3.1) as VSM 1.6. Dosimetric data were measured to commission the treatment planning system (TPS) and the VSM adapted to account for the lack of angular differential absorption and general beam hardening. The model was then tested using standard water phantom measurements and also by creating IMRT plans for a range of clinical cases.Results:The results show that the VSM implementation handles the FFF beams very well, with an uncertainty between measurement and calculation of <1% which is comparable to conventional flattened beams. All IMRT beams passed standard quality assurance tests with >95% of all points passing gamma analysis (γ < 1) using a 3%/3 mm tolerance.Conclusions:The virtual source model for flattened beams was successfully adapted to a flattening filter free beam production. Water phantom and patient specific QA measurements show excellent results, and comparisons of IMRT plans generated in conventional and FFF mode are underway to assess dosimetric uncertainties and possible improvements in dose calculation and delivery.
Investigating the dosimetric and tumor control consequences of prostate seed loss and migration
Authors: Knaup Courtney , Mavroidis Panayiotis , Esquivel Carlos , Stathakis Sotirios , Swanson Gregory , Baltas Dimos , Papanikolaou Nikos 
Published: May 2012

Purpose:Low dose‐rate brachytherapy is commonly used to treat prostate cancer. However, once implanted, the seeds are vulnerable to loss and movement. The goal of this work is to investigate the dosimetric and radiobiological effects of the types of seed loss and migration commonly seen in prostate brachytherapy.Methods:Five patients were used in this study. For each patient three treatment plans were created using Iodine‐125, Palladium‐103, and Cesium‐131 seeds. The three seeds that were closest to the urethra were identified and modeled as the seeds lost through the urethra. The three seeds closest to the exterior of prostatic capsule were identified and modeled as those lost from the prostate periphery. The seed locations and organ contours were exported from Prowess and used by in‐house software to perform the dosimetric and radiobiological evaluation. Seed loss was simulated by simultaneously removing 1, 2, or 3 seeds near the urethra 0, 2, or 4 days after the implant or removing seeds near the exterior of the prostate 14, 21, or 28 days after the implant.Results:Loss of one, two or three seeds through the urethra results in aD90 reduction of 2%, 5%, and 7% loss, respectively. Due to delayed loss of peripheral seeds, the dosimetric effects are less severe than for loss through the urethra. However, while the dose reduction is modest for multiple lost seeds, the reduction in tumor control probability was minimal.Conclusions:The goal of this work was to investigate the dosimetric and radiobiological effects of the types of seed loss and migration commonly seen in prostate brachytherapy. The results presented show that loss of multiple seeds can cause a substantial reduction ofD90 coverage. However, for the patients in this study the dose reduction was not seen to reduce tumor control probability.
Radiobiology for eye plaque brachytherapy and evaluation of implant duration and radionuclide choice using an objective function
Authors: Gagne Nolan L. , Leonard Kara L. , Rivard Mark J. 
Published: May 2012

Purpose:Clinical optimization of Collaborative Ocular Melanoma Study (COMS) eye plaque brachytherapy is currently limited to tumor coverage, consensus prescription dosage, and dose calculations to ocular structures. The biologically effective dose (BED) of temporary brachytherapy treatments is a function of both chosen radionuclideR and implant duration T. This study endeavored to evaluate BED delivered to the tumor volume and surrounding ocular structures as a function of plaque position P, prescription dose, R, and T.Methods:Plaque‐heterogeneity‐corrected dose distributions were generated with MCNP5 for the range of currently available COMS plaques loaded with sources using three available low‐energy radionuclides. These physical dose distributions were imported into thePINNACLE3 treatment planning system using the TG‐43 hybrid technique and used to generate dose volume histograms for a T = 7 day implant within a reference eye geometry including the ciliary body, cornea, eyelid, foveola, lacrimal gland, lens, optic disc, optic nerve, retina, and tumor at eight standard treatment positions. The equation of Dale and Jones was employed to create biologically effective dose volume histograms (BEDVHs), allowing for BED volumetric analysis of all ROIs. Isobiologically effective prescription doses were calculated for T = 5 days down to 0.01 days, with BEDVHs subsequently generated for all ROIs using correspondingly reduced prescription doses. Objective functions were created to evaluate the BEDVHs as a function of R and T. These objective functions are mathematically accessible and sufficiently general to be applied to temporary or permanent brachytherapy implants for a variety of disease sites.Results:ReducingT from 7 to 0.01 days for a 10 mm plaque produced an average BED benefit of 26%, 20%, and 17% for 103Pd, 125I, and 131Cs, respectively, for all P; 16 and 22 mm plaque results were more position‐dependent. 103Pd produced a 16%–35% BED benefit over 125I, whereas 131Cs produced a 3%–7% BED detriment, independent of P, T, and plaque size. Additionally, corresponding organ at risk physical doses were lowest using 103Pd in all circumstances.Conclusions:The results suggest that shorter implant durations may correlate with more favorable outcomes compared to 7 day implants when treating small or medium intraocular lesions. The data also indicate that implant duration may be safely reduced if the prescription physical dose is likewise diminished and that103Pd offers a substantial radiobiological benefit over 125I and 131Cs irrespective of plaque position, implant duration, and tumor size.