Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of the pediatric exclusivity provision on children's access to medicines.

AIMS To determine the paediatric licensing status in the USA, UK, Australia and New Zealand of the 79 medicines granted paediatric exclusivity in the USA, and to assess the importance of those medicines to paediatric practice. METHODS The medicines granted a patent extension in the USA as of 10 November 2003 were identified from the FDA website. Data on paediatric licensing were obtained from the Physicians Desk Reference (USA), the Electronic Medicines Compendium (UK), the Australian Prescription Products Guide (Australia) and the MedSafe website (New Zealand). A questionnaire was administered to seven paediatric consultants to assess the importance of the 79 PEMs for use in children. The questionnaire sought opinions on each drug, by age grouping, regarding: usefulness in patients with the condition, number of patients likely to be treated with each drug in a year, and acceptable therapeutic alternatives. RESULTS Fifty-eight (73%) of the medicines had attained paediatric licensing in the USA. Sixty were licensed for adults in all four countries and of these 45 (75%) were licensed for children under 12 years in the USA compared with 31 (52%) to 33 (55%) for the other three countries. The proportion of these medicines licensed for children under 1 month, under 2 years and under 6 years of age ranged from 10% to 58% and there were no significant differences between the countries. For all four countries perceived usefulness and predicted numbers of patients both had some influence on the odds of a medicine having paediatric licensing. CONCLUSIONS Improvements in licensing of some medicines for children have occurred in the USA, relative to the UK, Australia and New Zealand, subsequent to the Paediatric Exclusivity Provision. Improvements occurred for children over the age of six, but not for younger children.
Applications of Microstructured Silicon Wafers as Internal Reflection Elements in Attenuated Total Reflection Fourier Transform Infrared Spectroscopy

A novel internal reflection element (IRE) for attenuated total reflection Fourier transform infrared (ATR-FT-IR) spectral acquisition is introduced and applied for several surface-sensitive measurements. It is based on microstructured double-side-polished (100) silicon wafers with v-shaped grooves of {111} facets on their backside. These facets of the so-called “microstructured single-reflection elements” (mSRE) are formed by a crystal-oriented anisotropic wet etching process within a conventional wafer structuring process. They are used to couple infrared radiation into and out of the IRE. In contrast to the application of the commonly used silicon multiple-reflection elements (MRE), the new elements provide single-reflection ATR measurements at the opposite wafer side by using simple reflection accessories without any special collimation. Due to the short light path, the spectral range covers the entire mid-infrared region with a high optical throughput, including the range of silicon lattice vibrations from 300 to 1500 cm−1. In addition to typical ATR applications, i.e., the measurement of bulk liquids and soft materials, the new reflection elements can be effectively used and customer-specifically designed for in situ and ex situ investigations of aqueous solutions, thin films, and monolayers on Si. Examples presented in this article are in situ etching of native as well as thermal SiO2 and characterization of polydimethylsiloxane (PDMS) films on Si under various measuring conditions.
Regulated Payments for Living Kidney Donation: An Empirical Assessment of the Ethical Concerns

BACKGROUND Although regulated payments to encourage living kidney donation could reduce morbidity and mortality among patients waiting for a kidney transplant, doing so raises several ethical concerns. OBJECTIVE To determine the extent to which the 3 main concerns with paying kidney donors might manifest if a regulated market were created. DESIGN Cross-sectional study of participants' willingness to donate a kidney in 12 scenarios. SETTING Regional rail and urban trolley lines in Philadelphia County, Philadelphia, Pennsylvania. PARTICIPANTS Of 550 potential participants, 409 completed the questionnaire (response rate, 74.4%); 342 of these participants were medically eligible to donate. INTERVENTION Across scenarios, researchers experimentally manipulated the amount of money that participants would receive, the participants' risk for subsequently developing kidney failure themselves, and who would receive the donated kidney. MEASUREMENTS The researchers determined whether payment represents an undue inducement by evaluating participants' sensitivity to risk in relation to the payment offered or an unjust inducement by evaluating participants' sensitivity to payment as a function of their annual income. The researchers also evaluated whether introducing payment would hinder altruistic donations by comparing participants' willingness to donate altruistically before versus after the introduction of payments. RESULTS Generalized estimating equation models revealed that participants' willingness to donate increased significantly as their risk for kidney failure decreased, as the payment offered increased, and when the kidney recipient was a family member rather than a patient on a public waiting list (P < 0.001 for each). No statistical interactions were identified between payment and risk (odds ratio, 1.00 [95% CI, 0.96 to 1.03]) or between payment and income (odds ratio, 1.01 [CI, 0.99 to 1.03]). The proximity of these estimates to 1.0 and narrowness of the CIs suggest that payment is neither an undue nor an unjust inducement, respectively. Alerting participants to the possibility of payment did not alter their willingness to donate for altruistic reasons (P = 0.40). LIMITATION Choices revealed in hypothetical scenarios may not reflect real-world behaviors. CONCLUSION Theoretical concerns about paying persons for living kidney donation are not corroborated by empirical evidence. A real-world test of regulated payments for kidney donation is needed to definitively show whether payment provides a viable and ethical method to increase the supply of kidneys available for transplantation. PRIMARY FUNDING SOURCE None.
THE NUSTAR VIEW OF A QPO EVOLUTION OF GRS 1915+105

We report a timing analysis of the black hole binary GRS 1915+105 with the Nuclear Spectroscopic Telescope Array Observatory. A strong type-C quasi-periodic oscillation (QPO) below 2 Hz appears in the power density spectrum during the whole observation, whose frequency is correlated with the 3–25 keV count rate. The QPO shows a sudden increase in frequency along with an increase in flux and a softening of the spectrum. We discuss the possible origin of the QPO and the reasons that lead to the QPO frequency variation. It is suggested that the reflection component has little influence on QPO frequency and the increase in QPO frequency could be associated with the inward motion of the outer part of the disk.
An FMRI auditory oddball study of combined-subtype attention deficit hyperactivity disorder.

OBJECTIVE Studies of attention deficit hyperactivity disorder (ADHD) have reliably found reduced amplitude event-related potentials (ERPs) measuring attention-related brain function, indicating impairment in the brain's ability to automatically orient attention to odd or novel environmental stimuli and to represent that information in working memory. However, the relationship between abnormal neurocognition and dysfunction in specific brain regions in ADHD remains unclear. METHOD The authors used functional magnetic resonance imaging (fMRI) to identify brain regions with abnormal hemodynamic activity during processing of target and novelty oddball stimuli that engage attention. Forty-six boys 11-18 years of age participated in the study, including 23 diagnosed as having ADHD with hyperactivity and impulsivity (combined type) and 23 demographically matched control subjects. Event-related fMRI data were collected while participants performed a three-stimulus auditory oddball task. Hemodynamic activity was compared between ADHD participants and control subjects in brain regions previously linked to P3 ERPs. RESULTS Participants with ADHD showed deficits in brain activity elicited by infrequent attentionally engaging stimuli in regions associated with attentional orienting and working-memory cognitive processes. These deficits co-occurred with highly variable and slow task performance. CONCLUSIONS This study links ADHD attentional orienting and working-memory deficits to dysfunction in specific cortical brain regions. The results indicate that ADHD pathophysiology impairs brain systems that are important for allocating attention and using cognitive representations to guide cognition and behavior. Attention-related neural dysfunction is thus an important factor to consider in neurobiological theories of ADHD.
Sub-10-nm Tunnel Field-Effect Transistor With Graded Si/Ge Heterojunction

This study presents a new sub-10-nm tunnel field-effect transistor (TFET) with bandgap engineering using a graded Si/Ge heterojunction. Both the height and width of the tunneling barrier are highly controlled by applying gate voltages to ensure a near ideal sub-5-mV/dec switching of scaled sub-10-nm TFETs at 300 K. This study performed a 2-D simulation to elucidate p-body graded Si/Ge heterojunction TFET devices from 50 to 5 nm. The on-state tunneling barrier around the source was narrowed and lowered to demonstrate a high on-current; simultaneously, the off-state tunneling barrier was raised and extended into the drain to control the short-channel effect and ambipolar leakage current. The shorter the length is, the more abrupt is the switching. The breakthrough in subthreshold swing and short-channel effect make the graded Si/Ge TFET highly promising as an ideal green transistor into sub-10-nm regimes.
Comparative analysis of common CFTR polymorphisms poly-T, TG-repeats and M470V in a healthy Chinese population.

AIM To investigate the three important cystic fibrosis transmembrane conductance regulator (CFTR) haplotypes poly-T, TG-repeats and the M470V polymorphisms in the Chinese population, and to compare their distribution with that in Caucasians and other Asian populations. METHODS Genomic DNA was extracted from blood leukocytes. Exons 9 and 10 of the CFTR gene were obtained through polymerase chain reaction (PCR). Exon 9 DNA sequences were directly detected by an automated sequencer and poly-T and TG-repeats were identified by direct sequence analysis. Pure exon 10 PCR-amplified products were digested by HphI restriction enzyme and the M470V mutation was detected by the AGE photos of digestion products. RESULTS T7 was the most common (93.6%) haplotype and the (TG)11 frequency of 57.2% and (TG)12 frequency of 40.9% were dominant haplotypes in the junction of intron 8 (IVS-8) and exon 9. The frequency of T5 was 3.8% and all T5 allele tracts (10 alleles) were joined with (TG)12. Four new alleles of T6 (1.5%) were found in three healthy individuals. In exon 10, the V allele (56.1%) was slightly more frequent than the M allele (43.9%), and the M/V (45.5%) was the dominant genotype in these individuals. The three major haplotypes T7-(TG)11-V470, T7-(TG)12-M470 and T7-TG11-M470 were related to nearly 86.0% of the population. CONCLUSION The polymorphisms of poly-T, TG-repeats, and M470V distribution were similar to those in other East Asians, but they had marked differences in frequency from those single haplotype polymorphisms or linkage haplotypes in Caucasians. Thus, they may be able to explain the low incidence of CF and CF-like diseases in Asians.
Chaperones of the type III secretion pathway: jacks of all trades

The type III secretion (TTS) pathway is used by many Gram‐negative bacteria to inject virulence proteins into cells of their host. The activity of the TTS apparatus is controlled by external signals and, in certain conditions, production and secretion are not coupled. Storage of some proteins before secretion involves their association with specific chaperones. Three classes of TTS chaperones have been distinguished according to whether they associate with: (i) one; (ii) several effector proteins; or (iii) the two translocators that allow passage of effectors across the membrane of eukaryotic cells. These chaperones are required for stabilization of their substrate(s) and prevention of their premature interactions with other partners during storage. They also play a role in secretion of their substrate(s). Some chaperones are also involved in transcriptional regulation of certain genes in response to the activity of secretion. The flagellar export apparatus is closely related to the TTS apparatus and some proteins of the flagellar export system have also been proposed to be chaperones that prevent premature interactions between the flagellum subunits.
Defining Dimensions of Patient Satisfaction with Telemedicine: An Analysis of Existing Measurement Instruments

As telemedicine usage continues to grow there is a need to ensure the means are available to evaluate their success. Patient satisfaction can play a key role in determining the success of telemedicine projects. However, satisfaction remains loosely defined and there are no commonly accepted views on what it consists of. A lack of well-defined dimensions for measuring telemedicine satisfaction can make it difficult to interpret and compare results. By using a grounded theory approach for the analysis of existing patient satisfaction instruments, this research has identified several dimensions for describing patient satisfaction with telemedicine. In an effort to define these dimensions, this research examines their relationship to the existing telemedicine, information systems, and healthcare literature. In total 18 first level constructs, and 4 second order constructs were created for describing these dimensions and are defined in this research.
Ganglioside promotes the bridging of sciatic nerve defects in cryopreserved peripheral nerve allografts

Previous studies have shown that exogenous gangliosides promote nervous system regeneration and synapse formation. In this study, 10 mm sciatic nerve segments from New Zealand rabbits were thawed from cryopreservation and were used for the repair of left sciatic nerve defects through allograft bridging. Three days later, 1 mL ganglioside solution (1 g/L) was subcutaneously injected into the right hind leg of rabbits. Compared with non-injected rats, muscle wet weight ratio was increased at 2–12 weeks after modeling. The quantity of myelinated fibers in regenerated sciatic nerve, myelin thickness and fiber diameter were elevated at 4–12 weeks after modeling. Sciatic nerve potential amplitude and conduction velocity were raised at 8 and 12 weeks, while conduction latencies were decreased at 12 weeks. Experimental findings indicate that ganglioside can promote the regeneration of sciatic nerve defects after repair with cryopreserved peripheral nerve allografts.
A Discrete Time, Nested Cost Operator Approach to the Dynamic Network User Equilibrium Problem

In this paper we formulate the dynamic network user equilibrium problem as a variational inequality problem in discrete time in terms of unit path cost functions. We then show how arc exit flow functions and nested cost operators can be used to calculate unit path costs given the departure time and route choices of network users. We also demonstrate that, assuming certain regularity conditions hold, a discrete time dynamic network user equilibrium is guaranteed to exist. Finally, a heuristic algorithm and numerical results are presented.
A Diffusion Gradient Chamber for Studying Microbial Behavior and Separating Microorganisms

The natural habitats of most microbes are dynamic and include spatial gradients of growth substrates, electron acceptors, pH, salts, and inhibitory compounds. To mimic this diffusive aspect of nature, we developed an analytical diffusion gradient chamber (DGC) that can be used to separate, enrich for, isolate, and study the behavior of microorganisms. The chamber is a polycarbonate box containing an arena (5 by 5 by 2 cm) into which is cast a semisolid growth medium. Continuously replenished solute reservoirs positioned on each side of the arena but separated from it by a porous membrane enable the formation throughout the gel of multiple, intersecting gradients of solutes in two dimensions. With glucose as the solute, a gradient which spanned a 100-fold range in concentration was established across the arena in about 4 days. The shape of the glucose gradient was accurately predicted by a mathematical model based on Fickian diffusion. The growth and migratory behavior of Escherichia coli in response to imposed gradients of attractants (aspartate, α-methyl aspartate, and serine) and a repellent (valine) were examined. Cells responded in predictable ways to such gradients by forming distinctive growth and migration patterns in the DGC. This was true for wild-type E. coli as well as specific chemotaxis and motility mutants. The patterns yielded information about the threshold concentration of chemoeffectors needed to elicit a response as well as their saturating concentration. It was also evident that the metabolism of attractants significantly affected the gradients and, hence, the movement of cells. Finally, it was possible to separate E. coli and Pseudomonas fluorescens in the DGC on the basis of their differential responses to gradients of various chemoeffectors.
Complexity of the decision-making process of ambulance staff for assessment and referral of older people who have fallen: a qualitative study

Background Older people who fall commonly present to the emergency ambulance service, and approximately 40% are not conveyed to the emergency department (ED), despite an historic lack of formal training for such decisions. This study aimed to understand the decision-making processes of emergency ambulance staff with older people who have fallen. Methods During 2005 ambulance staff in London tested a clinical assessment tool for use with the older person who had fallen. Documented use of the tool was low. Following the trial, 12 staff participated in semistructured interviews. Interviews were recorded and transcribed. Thematic analysis was carried out. Results The interviews revealed a similar assessment and decision-making process among participants: Prearrival: forming an early opinion from information from the emergency call. Initial contact: assessing the need for any immediate action and establishing a rapport. Continuing assessment: gathering and assimilating medical and social information. Making a conveyance decision: negotiation, referral and professional defence, using professional experience and instinct. Conclusions An assessment process was described that highlights the complexity of making decisions about whether or not to convey older people who fall and present to the emergency ambulance service, and a predominance of informal decision-making processes. The need for support for ambulance staff in this area was highlighted, generating a significant challenge to those with education roles in the ambulance service. Further research is needed to look at how new care pathways, which offer an alternative to the ED may influence decision making around non-conveyance.
Giving Voice to Persons Living With Dementia: The Researcher’s Opportunities and Challenges

Few qualitative studies have examined the experiences of persons living with dementia and little has been written about the opportunities and challenges for the researchers. This article challenges the assumption of dwindling personhood among persons with dementia. Methodological challenges which may be encountered by qualitative researchers are outlined and specific strategies for addressing these challenges are described including: modifying consent/assent procedures, adjusting sample size, facilitating communication, and making the most of the data.
Microplastic pollution in St. Lawrence River sediments

Although widely detected in marine ecosystems, microplastic pollution has only recently been documented in freshwater environments, almost exclusively in surface waters. Here, we report microplastics (polyethylene microbeads, 0.40–2.16 mm diameter) in the sediments of the St. Lawrence River. We sampled 10 freshwater sites along a 320 km section from Lake St. Francis to Quebec City by passing sediment collected from a benthic grab through a 500 μm sieve. Microbeads were discovered throughout this section, and their abundances varied by four orders of magnitude across sites. Median and mean (±1 SE) densities across sites were 52 microbeads·m−2 and 13 832 (±13 677) microbeads·m−2, respectively. The highest site density was 1.4 × 105 microbeads·m−2 (or 103 microbeads·L−1), which is similar in magnitude to microplastic concentrations found in the world’s most contaminated marine sediments. Mean diameter of microbeads was smaller at sites receiving municipal or industrial effluent (0.70 ± 0.01 mm) than at non-e.
Mobile Network-Connected Drones: Field Trials, Simulations, and Design Insights

Drones are increasingly used in a wide variety of industries and services and are delivering profound socioeconomic benefits. Technology needs to be in place to ensure the safe operation and management of this growing fleet of drones. In the past decades, mobile networks have connected tens of billions of devices on the ground and are now ready to connect drones flying in the sky. In this article, we share some of our findings concerning cellular connectivity for low-altitude drones. We first present and analyze field measurement data collected during drone flights in a commercial LTE network. We then present simulation results to shed light on the performance of a network when it is serving many drones simultaneously over a wide area. The results, analysis, and design insights presented here help enhance understanding of the applicability of and performance concerns related to providing mobile connectivity for lowaltitude drones.
syn-Selective rhodium(I)-catalyzed allylations of ketimines proceeding through a directed C-H activation/allene addition sequence.

Rhodium(I)-catalyzed C-H functionalization of aryl ketimines and subsequent carborhodation of a terminal allene resulted in the formation of allyl rhodium intermediates, which underwent allylation of the imine to give cyclized products, e.g., I, with high regioselectivity and diastereoselectivity. Preliminary attempts to develop an enantioselective variant were also successful.