Accessing Data: Methods for understanding mobile technology use

Mobile devices, applications and services have become integrated into people’s dailylives on a personal and professional level. Although traditional research methods arebeing used to understand the use of mobile devices and applications, methodologicalchallenges still exist. Researchers have responded to these challenges in a variety ofways, with an emphasis on developing methods that enable new ways of accessing,making available and collecting data about mobile technology use. This paper identifies,defines, describes and presents, a preliminary framework for understanding themethodological responses emerging in current Mobile Human Computer Interaction(Mobile HCI) research

Eomeshi NK Cells in Human Liver Are Long-Lived and Do Not Recirculate but Can Be Replenished from the Circulation.

Human liver contains an Eomes(hi) population of NK cells that is not present in the blood. In this study, we show that these cells are characterized by a molecular signature that mediates their retention in the liver. By examining liver transplants where donors and recipients are HLA mismatched, we distinguish between donor liver-derived and recipient-derived leukocytes to show that Eomes(lo) NK cells circulate freely whereas Eomes(hi) NK cells are unable to leave the liver. Furthermore, Eomes(hi) NK cells are retained in the liver for up to 13 y. Therefore, Eomes(hi) NK cells are long-lived liver-resident cells. We go on to show that Eomes(hi) NK cells can be recruited from the circulation during adult life and that circulating Eomes(lo) NK cells are able to upregulate Eomes and molecules mediating liver retention under cytokine conditions similar to those in the liver. This suggests that circulating NK cells are a precursor of their liver-resident counterparts

Development, implementation and initial feasibility testing of the MediEmo mobile application to provide support during medically assisted reproduction.

STUDY QUESTION Is it possible to develop a patient smartphone application for medically assisted reproduction (MAR) that is acceptable to patients and fertility staff? SUMMARY ANSWER Staff and patients responded positively to the MediEmo smartphone application, perceiving it to be acceptable and feasible to implement in a busy clinic. WHAT IS KNOWN ALREADY Digital tools are increasingly popular to provide practical, administrative and psychological support alongside medical treatments. Apps and other digital tools have been developed for use alongside MAR but there is very limited research on the development or acceptability and feasibility of these tools. STUDY DESIGN, SIZE, DURATION Mixed methods research. This article outlines the development phase of the MediEmo smartphone app, which was guided by the Medical Research Council development framework for complex interventions. The resulting MediEmo app was then implemented into a single centre for MAR in the UK, acceptability evaluated and feasibility explored among 1106 potential participants undertaking IVF cycles. PARTICIPANTS/MATERIALS, SETTING, METHODS Consultation and data collection took part at a single mid-sized urban fertility clinic. Development of the MediEmo smartphone application took place during 2013 to 2017. Implementation of the MediEmo took place from June 2017 to September 2020. The MediEmo app comprises three functions (six features) namely medication management (medication timeline, messaging), mood management (emotional tracking, coping support) and functional support (frequently asked questions, symptom checker). Data on age, fertility diagnosis, anti-Müllerian hormone level were collected about the users of the MediEmo in addition to MediEmo usage data and attitudes towards the MediEmo smartphone application. MAIN RESULTS AND THE ROLE OF CHANCE Informed by the developmental process described, MediEmo is an app combining patient medication diary management and ease of integration into clinic systems with emotional support, emotional tracking and data capture. This study demonstrates acceptability and feasibility of MediEmo, with good uptake (79.8%), mood data sensitivity and reliability and positive feedback. LIMITATIONS, REASONS FOR CAUTION Single centre, small number of users in questionnaire studies. WIDER IMPLICATIONS OF THE FINDINGS The findings suggest smartphone apps can contribute to fertility care and that patient engagement is high. Evaluation of any apps introduced into clinical pathways should be encouraged to promote development of the most useful digital tools for fertility patients. STUDY FUNDING/COMPETING INTEREST(S) This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector. Outside of the submitted work, J.B. reports personal speaker fees from Merck KGaA, Darmstadt, Germany, Merck AB an affiliate of Merck KGaA, Darmstadt Germany, Theramex, MedThink China, Ferring Pharmaceuticals A/S, grant from Merck Serono Ltd, outside the submitted work and that she is co-developer of Fertility Quality of Life (FertiQoL) and MediEmo app; N.M and C.Y are minority shareholders and J.B.'s University (Cardiff University) owns one third of shares. None of the shareholders benefitted financially from MediEmo. I.R., C.H. and K.Y.B.N. declare no conflicts of interest

Priority Medicines for Maternal and Child Health: A Global Survey of National Essential Medicines Lists

BACKGROUND: In April 2011, the World Health Organization (WHO) published a list of "priority medicines" for maternal and child health based on 1) the global burden of disease and 2) evidence of efficacy and safety. The objective of this study was to examine the occurrence of these priority medicines on national essential medicines lists. METHODS AND FINDINGS: All essential medicines lists published since 1999 were selected from the WHO website collection. The most-up-to date list for each country was then selected, resulting in 89 unique country lists. Each list was evaluated for inclusion of medicines (chemical entity, concentration, and dosage form) on the Priority Medicines List. There was global variation in the listing of the Priority Medicines. The most frequently listed medicine was paracetamol, on 94% (84/89) of lists. Sodium chloride, gentamicin and oral rehydration solution were on 93% (83/89) of lists. The least frequently listed medicine was the children's antimalarial rectal artesunate, on 8% of lists (7/89); artesunate injection was on 16% (14/89) of lists. Pediatric artemisinin combination therapy, as dispersible tablets or flexible oral solid dosage form, appeared on 36% (32/89) of lists. Procaine benzylpenicillin, for treatment of pediatric pneumonia and neonatal sepsis, was on 50% (45/89) of the lists. Zinc, for treatment of diarrhoea in children, was included on only 15% (13/89) of lists. For prevention and treatment of postpartum hemorrhage in women, oxytocin was more prevalent on the lists than misoprostol; they were included on 55 (62%) and 31 (35%) of lists, respectively. Cefixime, for treatment of uncomplicated anogenital gonococcal infection in woman was on 26% (23/89) of lists. Magnesium sulfate injection for treatment of severe pre-eclampsia and eclampsia was on 50% (45/89) of the lists. CONCLUSIONS: The findings suggest that countries need to urgently amend their lists to provide all priority medicines as part of the efforts to improve maternal and child health

Proton Magnetic Resonance Spectroscopy Lactate/N-Acetylaspartate Within 48 h Predicts Cell Death Following Varied Neuroprotective Interventions in a Piglet Model of Hypoxia–Ischemia With and Without Inflammation-Sensitization

Despite therapeutic hypothermia, survivors of neonatal encephalopathy have high rates of adverse outcome. Early surrogate outcome measures are needed to speed up the translation of neuroprotection trials. Thalamic lactate (Lac)/N-acetylaspartate (NAA) peak area ratio acquired with proton (1H) magnetic resonance spectroscopy (MRS) accurately predicts 2-year neurodevelopmental outcome. We assessed the relationship between MR biomarkers acquired at 24–48 h following injury with cell death and neuroinflammation in a piglet model following various neuroprotective interventions. Sixty-seven piglets with hypoxia–ischemia, hypoxia alone, or lipopolysaccharide (LPS) sensitization were included, and neuroprotective interventions were therapeutic hypothermia, melatonin, and magnesium. MRS and diffusion-weighted imaging (DWI) were acquired at 24 and 48 h. At 48 h, experiments were terminated, and immunohistochemistry was assessed. There was a correlation between Lac/NAA and overall cell death [terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)] [mean Lac/NAA basal ganglia and thalamus (BGT) voxel r = 0.722, white matter (WM) voxel r = 0.784, p < 0.01] and microglial activation [ionized calcium-binding adapter molecule 1 (Iba1)] (BGT r = −0.786, WM r = −0.632, p < 0.01). Correlation with marker of caspase-dependent apoptosis [cleaved caspase 3 (CC3)] was lower (BGT r = −0.636, WM r = −0.495, p < 0.01). Relation between DWI and TUNEL was less robust (mean diffusivity BGT r = −0.615, fractional anisotropy BGT r = 0.523). Overall, Lac/NAA correlated best with cell death and microglial activation. These data align with clinical studies demonstrating Lac/NAA superiority as an outcome predictor in neonatal encephalopathy (NE) and support its use in preclinical and clinical neuroprotection studies

Quantification of the severity of hypoxic-ischemic brain injury in a neonatal preclinical model using measurements of cytochrome-c-oxidase from a miniature broadband-near-infrared spectroscopy system

We describe the development of a miniaturized broadband near-infrared spectroscopy system (bNIRS), which measures changes in cerebral tissue oxyhemoglobin (  [  HbO₂ ]  ) and deoxyhemoglobin ([HHb]) plus tissue metabolism via changes in the oxidation state of cytochrome-c-oxidase ([oxCCO]). The system is based on a small light source and a customized mini-spectrometer. We assessed the instrument in a preclinical study in 27 newborn piglets undergoing transient cerebral hypoxia-ischemia (HI). We aimed to quantify the recovery of the HI insult and estimate the severity of the injury. The recovery in brain oxygenation (Δ  [  HbDiff  ]    =  Δ  [  HbO₂  ]    −  Δ  [  HHb  ]  ), blood volume (Δ  [  HbT  ]    =  Δ  [  HbO₂  ]    +  Δ  [  HHb  ]  ), and metabolism (Δ  [  oxCCO  ]  ) for up to 30 min after the end of HI were quantified in percentages using the recovery fraction (RF) algorithm, which quantifies the recovery of a signal with respect to baseline. The receiver operating characteristic analysis was performed on bNIRS-RF measurements compared to proton (H1) magnetic resonance spectroscopic (MRS)-derived thalamic lactate/N-acetylaspartate (Lac/NAA) measured at 24-h post HI insult; Lac/NAA peak area ratio is an accurate surrogate marker of neurodevelopmental outcome in babies with neonatal HI encephalopathy. The Δ  [  oxCCO  ]  -RF cut-off threshold of 79% within 30 min of HI predicted injury severity based on Lac/NAA with high sensitivity (100%) and specificity (93%). A significant difference in thalamic Lac/NAA was noticed (p  <  0.0001) between the two groups based on this cut-off threshold of 79% Δ  [  oxCCO  ]  -RF. The severe injury group (n  =  13) had ∼30  %   smaller recovery in Δ  [  HbDiff  ]  -RF (p  =  0.0001) and no significant difference was observed in Δ  [  HbT  ]  -RF between groups. At 48 h post HI, significantly higher P31-MRS-measured inorganic phosphate/exchangeable phosphate pool (epp) (p  =  0.01) and reduced phosphocreatine/epp (p  =  0.003) were observed in the severe injury group indicating persistent cerebral energy depletion. Based on these results, the bNIRS measurement of the oxCCO recovery fraction offers a noninvasive real-time biomarker of brain injury severity within 30 min following HI insult

Mutation-Independent Allele-Specific Editing by CRISPR-Cas9, a Novel Approach to Treat Autosomal Dominant Disease

CRISPR-Cas9 provides a tool to treat autosomal dominant disease by non-homologous end joining (NHEJ) gene disruption of the mutant allele. In order to discriminate between wild-type and mutant alleles, Streptococcus pyogenes Cas9 (SpCas9) must be able to detect a single nucleotide change. Allele-specific editing can be achieved by using either a guide-specific approach, in which the missense mutation is found within the guide sequence, or a protospacer-adjacent motif (PAM)-specific approach, in which the missense mutation generates a novel PAM. While both approaches have been shown to offer allele specificity in certain contexts, in cases where numerous missense mutations are associated with a particular disease, such as TGFBI (transforming growth factor β-induced) corneal dystrophies, it is neither possible nor realistic to target each mutation individually. In this study, we demonstrate allele-specific CRISPR gene editing independent of the disease-causing mutation that is capable of achieving complete allele discrimination, and we propose it as a targeting approach for autosomal dominant disease. Our approach utilizes natural variants in the target region that contain a PAM on one allele that lies in cis with the causative mutation, removing the constraints of a mutation-dependent approach. Our innovative patient-specific guide design approach takes into account the patient’s individual genetic make-up, allowing on- and off-target activity to be assessed in a personalized manner

A comparison of game-play characteristics between elite youth and senior Australian National Rugby League competitions

Objectives: To compare game-play characteristics between elite youth and senior Australian National Rugby League (NRL) competitions. Design: Longitudinal observational. Methods: The dataset consisted of 12 team performance indicators (e.g., ‘all runs’, ‘offloads’ and ‘tackles’) extracted from all 2016 national under 20 (U20) competition (elite youth; n = 372 observations) and National Rugby League (NRL) (elite senior; n = 378 observations) matches. Data was classified according to competition (Two levels: U20 and NRL) and modelled using two techniques. Firstly, non-metric multidimensional scaling resolved multivariate competition (dis)similarity, visualised using a two-dimensional ordination. Secondly, a conditional interference (CI) classification tree was grown to reveal the performance indicators most capable of explaining competition level. Results: Non-metric multidimensional scaling revealed high competition dissimilarity, with U20 and NRL teams orienting distinctive positions on the first dimension of the ordination surface. Five team performance indicators were retained within the CI tree (‘all runs’, ‘tackle breaks’, ‘tackles’, ‘missed tackles’, and ‘kicks’), which correctly classified 79% of the U20 observations and 93% of the NRL observations. Conclusions: Multivariate differences between elite youth and senior rugby league competitions were identified. Specifically, NRL game-play was classified by a greater number of ‘all runs’, and ‘tackles’ and a lower number of ‘missed tackles’ relative to the U20 competition. Given the national U20 competition is purported to assist with the development of prospective NRL players, junior coaches may consider training interventions that primarily aid the tackling capacities of players. This may subsequently assist with talent development and player progression in Australian rugby league

Linking dwarf galaxies to halo building blocks with the most metal-poor star in Sculptor

Current cosmological models indicate that the Milky Way's stellar halo was assembled from many smaller systems. Based on the apparent absence of the most metal-poor stars in present-day dwarf galaxies, recent studies claimed that the true Galactic building blocks must have been vastly different from the surviving dwarfs. The discovery of an extremely iron-poor star (S1020549) in the Sculptor dwarf galaxy based on a medium-resolution spectrum cast some doubt on this conclusion. However, verification of the iron-deficiency and measurements of additional elements, such as the alpha-element Mg, are mandatory for demonstrating that the same type of stars produced the metals found in dwarf galaxies and the Galactic halo. Only then can dwarf galaxy stars be conclusively linked to early stellar halo assembly. Here we report high-resolution spectroscopic abundances for 11 elements in S1020549, confirming the iron abundance of less than 1/4000th that of the Sun, and showing that the overall abundance pattern mirrors that seen in low-metallicity halo stars, including the alpha-elements. Such chemical similarity indicates that the systems destroyed to form the halo billions of years ago were not fundamentally different from the progenitors of present-day dwarfs, and suggests that the early chemical enrichment of all galaxies may be nearly identical.Comment: 16 pages, including 2 figures. Accepted for publication in Nature. It is embargoed for discussion in the press until formal publication in Natur