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C A Ryan

Publications and source records attributed to C A Ryan.

At least 19 recordsLinked to original sources

Persistent lactic acidosis in neonatal hypoxic-ischaemic encephalopathy correlates with EEG grade and electrographic seizure burden.

BACKGROUND: Predicting at birth which infants with perinatal hypoxic-ischaemic injury will progress to significant encephalopathy remains a challenge. OBJECTIVE: To determine whether lactic acidosis at birth in asphyxiated neonates could predict the grade of EEG encephalopathy by examining the relationship between time taken for the normalisation of lactate, severity of encephalopathy and seizure burden. METHODS: Continuous early video-EEG monitoring was performed in babies at risk for hypoxic-ischaemic encephalopathy. Encephalopathy was graded from the EEG data. Total seizure burden (seconds) was calculated for each baby. Initial blood gas measurements of pH, base deficit and lactate were taken within 30 minutes of delivery. Time to normal serum lactate was determined in hours from birth for each infant. RESULTS: All 50 term infants had raised initial serum lactate (median (lower, upper quartiles) 11.7 (10.2, 14.9)). There were no significant differences between the initial serum lactate, pH and base deficit in infants with normal/mildly abnormal (n = 24), moderately abnormal (n = 14), severely abnormal (n = 5) and inactive EEGs (n = 7). Time to normal lactate varied significantly with EEG grade (median (lower, upper quartile) 6.0 (4.1, 9.5) for mild/normal EEG, 13.5 (6.8, 23.5) moderate EEG, 41.5 (30.0, 55.5) severe group, 12.0 (8.1, 21.5) inactive group; p<0.001). Time to normal lactate correlated significantly with EEG seizure burden (seconds; R = 0.446, p = 0.002). Mean (SD) time to normal lactate was 10.0 (7.2) hours in infants who did not have seizures and 27.3 (19.0) hours in the 13 infants with electrographic seizures (p = 0.002). CONCLUSIONS: Serum lactate levels in the first 30 minutes of life do not predict the severity of the ensuing encephalopathy. In contrast, sustained lactic acidosis is associated with severe encephalopathy on EEG and correlates with seizure burden.

Acidosis, Lactic↗

Benchmarking quantum control methods on a 12-qubit system.

In this Letter, we present an experimental benchmark of operational control methods in quantum information processors extended up to 12 qubits. We implement universal control of this large Hilbert space using two complementary approaches and discuss their accuracy and scalability. Despite decoherence, we were able to reach a 12-coherence state (or a 12-qubit pseudopure cat state) and decode it into an 11 qubit plus one qutrit pseudopure state using liquid state nuclear magnetic resonance quantum information processors.

Journal Article↗

The local lymph node assay in practice: a current regulatory perspective.

Following the formal acceptance of the local lymph node assay (LLNA) as an Organization for Economic Cooperation and Development (OECD) guideline in April 2002, the UK Health and Safety Executive (HSE) informed notifiers that this was now the method of choice for the assessment of skin sensitization potential under the EU notification scheme for new industrial chemicals (NONS). This paper summarizes the experience of the HSE for the 2-year period immediately following the issuing of this statement, during which 48 LLNA study reports were assessed for notification purposes. The issues discussed here include adherence to the OECD guideline, interpretation of results, and classification outcomes. Generally, notifying laboratories followed the OECD guideline successfully, with regard to the sex/ strain/numbers of mice used, the precise process used for measurement of cell proliferation, and the use of recommended vehicles and positive controls. Initially, use of the individual animal approach (measuring the cell proliferation in each animal rather than for a pooled dose group) highlighted problems caused by technical inexperience, but these were overcome by practice. Toxicity or irritation were found to be minor factors in dose selection; more important was the choice of vehicle to correctly maximize the test substance concentration, while maintaining appropriate application properties. Contrary to concerns that the LLNA would prove to be less sensitive or more sensitive than the traditionally used Guinea Pig Maximization Test (GPMT), the proportion of new substances classified as skin sensitizers was within the range observed in previous years. Although the sample size is relatively small, the experience of the HSE indicates that the LLNA is satisfactory for routine regulatory use.

Animals↗

Understanding the role of the qualified professional: a comparison of medical and dental students' attitudes.

UNLABELLED: The Royal College of Physicians & Surgeons of Canada developed a competency framework to assist future specialists in responding to challenges as health care providers. The CANMEDs project described 7 essential roles of Specialist Physicians include Health Advocate, Manager, Scholar, Medical Expert, Professional, Communicator and Collaborator (HMSEPC(2)). The object of the current study was to investigate whether medical students and dental students in Ireland recognised these responsibilities as essential to a qualified doctor/dentist. METHODS: Ninety-eight medical and forty-six dental students (year 1 and year 4) were asked to mind map the responsibilities of qualified doctors/dentists. The comments on the mind map were applied to one of the 7 CANMED roles. There were 484 comments from 128 students. Students had the greatest number of responses referring to the Medical and Dental Expert (257, 30.4%) and Professional (227, 26.9%) roles. This was followed by Communicator (130, 15.4%), Scholar (107, 12.7%) and Health Advocate (82, 9.7%) roles. There were relatively few responses relating to Manager (12, 1.4%) and Collaborator (i.e. teamwork) roles (30, 3.6%). There were no differences in responses between Dental Students and Medical Students and between 1 st year and 4th year students. Similarly there were no differences between the responses of Irish students (n =95; 68%) and International students (n =45; 32%) Students are aware of their responsibilities as Medical or Dental experts (diagnostic and therapeutic skills) for ethical and effective patient care (professional role). They are somewhat aware of the Communicator (therapeutic relationships and effective listening), Scholar (personal continuing education strategies) and Health Advocate (contribute to improved community health) roles. In general they have little concept of the importance of Management skills (utilising resources effectively), and of Collaboration (teamwork and consulting effectively with other physicians and health care professionals). Medical and Dental Educators and Curriculum Committees should address these important deficiencies.

Adolescent↗

Characterization of complex quantum dynamics with a scalable NMR information processor.

We present experimental results on the measurement of fidelity decay under contrasting system dynamics using a nuclear magnetic resonance quantum information processor. The measurements were performed by implementing a scalable circuit in the model of deterministic quantum computation with only one quantum bit. The results show measurable differences between regular and complex behavior and for complex dynamics are faithful to the expected theoretical decay rate. Moreover, we illustrate how the experimental method can be seen as an efficient way for either extracting coarse-grained information about the dynamics of a large system or measuring the decoherence rate from engineered environments.

Journal Article↗

Experimental implementation of heat-bath algorithmic cooling using solid-state nuclear magnetic resonance.

The counter-intuitive properties of quantum mechanics have the potential to revolutionize information processing by enabling the development of efficient algorithms with no known classical counterparts. Harnessing this power requires the development of a set of building blocks, one of which is a method to initialize the set of quantum bits (qubits) to a known state. Additionally, fresh ancillary qubits must be available during the course of computation to achieve fault tolerance. In any physical system used to implement quantum computation, one must therefore be able to selectively and dynamically remove entropy from the part of the system that is to be mapped to qubits. One such method is an 'open-system' cooling protocol in which a subset of qubits can be brought into contact with an external system of large heat capacity. Theoretical efforts have led to an implementation-independent cooling procedure, namely heat-bath algorithmic cooling. These efforts have culminated with the proposal of an optimal algorithm, the partner-pairing algorithm, which was used to compute the physical limits of heat-bath algorithmic cooling. Here we report the experimental realization of multi-step cooling of a quantum system via heat-bath algorithmic cooling. The experiment was carried out using nuclear magnetic resonance of a solid-state ensemble three-qubit system. We demonstrate the repeated repolarization of a particular qubit to an effective spin-bath temperature, and alternating logical operations within the three-qubit subspace to ultimately cool a second qubit below this temperature. Demonstration of the control necessary for these operations represents an important step forward in the manipulation of solid-state nuclear magnetic resonance qubits.

Journal Article↗

Pharmacokinetics and pharmacodynamics of pantoprazole in clinically normal neonatal foals.

REASONS FOR PERFORMING STUDY: Proton pump inhibitors (PPIs) are a mainstay of treatment for acid-related ulceration in man and horses. Currently, only an oral preparation of omeprazole is approved for use in horses in the USA. Intravenous administration of a PPI would provide a useful therapeutic alternative for those foals in which oral medication is not feasible. OBJECTIVE: To investigate the pharmacokinetics and pharmacodynamics of pantoprazole following i.v. or intragastric administration in healthy neonatal foals. METHODS: Seven healthy foals age 6-12 days at the start of the study were evaluated. Treatments included no drug administration, i.v. pantoprazole (1.5 mg/kg bwt) and intragastric pantoprazole (1.5 mg/kg bwt). Intragastric pH was recorded for 24 h after drug administration for pharmacodynamic evaluation. Plasma pantoprazole concentrations were measured using high-performance liquid chromatography. RESULTS: Plasma concentrations of pantoprazole were detectable at the 5 min sampling point following i.v. or intragastric administration. Bioavailability of intragastric-administered pantoprazole was 41%. Baseline mean hourly pH was 1.5-6.1. There was a statistically significant increase in mean hourly pH relative to untreated foals 2-24 h after i.v. or intragastric pantoprazole administration. CONCLUSIONS: Based on these data, i.v. or intragastric administration of pantoprazole results in a significant, prolonged increase in intragastric pH. POTENTIAL RELEVANCE: The i.v. formulation of pantoprazole may provide a clinically useful alternative means of acid suppression in foals unable to tolerate enteral administration of a PPI, such as those with pyloric outflow obstruction.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Mining the microbiota of the neonatal gastrointestinal tract for conjugated linoleic acid-producing bifidobacteria.

This study was designed to isolate different strains of the genus Bifidobacterium from the fecal material of neonates and to assess their ability to produce the cis-9, trans-11 conjugated linoleic acid (CLA) isomer from free linoleic acid. Fecal material was collected from 24 neonates aged between 3 days and 2 months in a neonatal unit (Erinville Hospital, Cork, Ireland). A total of 46 isolates from six neonates were confirmed to be Bifidobacterium species based on a combination of the fructose-6-phosphate phosphoketolase assay, RAPD [random(ly) amplified polymorphic DNA] PCR, pulsed-field gel electrophoresis (PFGE), and partial 16S ribosomal DNA sequencing. Interestingly, only 1 of the 11 neonates that had received antibiotic treatment produced bifidobacteria. PFGE after genomic digestion with the restriction enzyme XbaI demonstrated that the bifidobacteria population displayed considerable genomic diversity among the neonates, with each containing between one and five dominant strains, whereas 11 different macro restriction patterns were obtained. In only one case did a single strain appear in two neonates. All genetically distinct strains were then screened for CLA production after 72 h of incubation with 0.5 mg of free linoleic acid ml(-1) by using gas-liquid chromatography. The most efficient producers belonged to the species Bifidobacterium breve, of which two different strains converted 29 and 27% of the free linoleic acid to the cis-9, trans-11 isomer per microgram of dry cells, respectively. In addition, a strain of Bifidobacterium bifidum showed a conversion rate of 18%/microg dry cells. The ability of some Bifidobacterium strains to produce CLA could be another human health-promoting property linked to members of the genus, given that this metabolite has demonstrated anticarcinogenic activity in vitro and in vivo.

Aldehyde-Lyases↗

Comparison of three manual ventilation devices using an intubated mannequin.

OBJECTIVE: To compare three devices for manual neonatal ventilation. DESIGN: Participants performed a two minute period of ventilation using a self inflating device, an anaesthesia bag with attached manometer, and a Neopuff device. An intubated neonatal mannequin, approximating a 1 kg infant with functional lungs, was used for the study. Target ventilation variables included a rate of 40 breaths per minute, peak inspiratory pressure (PIP) of 20 cm H2O, and positive end expiratory pressure (PEEP) of 4 cm H2O. The circuit was attached to a laptop computer for data recording. RESULTS: Thirty five participants were enrolled, including consultant neonatologists, paediatricians, and anaesthetists, paediatric and anaesthetic registrars, and neonatal nurses. The maximum PIP recorded using the self inflating bag, anaesthetic bag, and Neopuff device were 75.9, 35.5, and 22.4 cm H2O respectively. There were significant differences between the devices for mean PIP (30.7, 18.1, and 20.1 cm H2O), mean PEEP (0.2, 2.8, and 4.4 cm H2O), mean airway pressure (7.6, 8.5, and 10.9 cm H2O), % total breaths < or = 21 cm H2O PIP (39%, 92%, and 98%), and % total breaths > or = 30 cm H2O PIP (45%, 0, and 0). There was no difference between doctors and allied health professionals for the variables examined. CONCLUSION: The anaesthetic bag with manometer and Neopuff device both facilitate accurate and reproducible manual ventilation. Self inflating devices without modifications are not as consistent by comparison and should incorporate a manometer and a PEEP device, particularly when used for resuscitation of very low birthweight infants.

Allied Health Personnel↗

Utility of historical vehicle-control data in the interpretation of the local lymph node assay.

The accepted approach to the interpretation of local lymph node assay (LLNA) data requires comparison of responses in the test groups with background activity found in concurrent vehicle-treated controls. However, of established value in the interpretation of toxicity test data is the use of historical control values that provide one criterion against which to judge the integrity of individual experiments. Specifically, the availability of robust and relevant historical control data permits examination of whether, in any individual experiment, control values fall within the expected range. With the most commonly used vehicle employed in the LLNA, acetone/olive oil (4 : 1) (v/v), the mean values, standard deviations and normal ranges are increasingly well established for a given laboratory, although there is some variation between laboratories, particularly with regard to expected ranges. Against this background, it is possible to identify (and, if appropriate, eliminate) a concurrent vehicle-control value that falls well outside the expected range. To explore critically the potential merits of this approach, one specific example is examined in detail.

Animals↗

High rates of sexually transmitted diseases among male transvestites in Jakarta, Indonesia.

Many male transvestites (waria) in Jakarta, Indonesia engage in unprotected receptive anal and oral intercourse with homosexual and bisexual men for pay. Although this behaviour clearly puts them at risk of sexually transmitted diseases (STDs), including HIV infection, little is known about the prevalence of STD among them. To learn the STD prevalence and its risk factors, we conducted an STD prevalence survey among waria in North Jakarta, Indonesia. From August to December 1999 we offered screening for rectal and pharyngeal infections with Neisseria gonorrhoeae (Ng), Chlamydia trachomatis (Ct) by DNA probe (GenProbe PACE 2) and for Treponema pallidum (Tp) by non-treponemal and treponemal serological tests. Of 296 participants (median age 28 years), 93% reported having been paid for sex. A total of 96% reported having had oral sex (median five times/week) and/or anal sex (median three times/week) in the last week. Ng was found in the rectum of 12.8% and the pharynx of 4.2%; Ct was found in 3.8% and 2.4%, respectively. A total of 43.6% had reactive non-treponemal and treponemal tests. Of the 129 with positive treponemal tests, 42.6% had non-treponemal test titres greater than 1:8. In the logistic regression model, waria who were younger (< or =25 years old) had a significantly 3.5 times risk of Ng and/or Ct infections than older waria (>25 years old). Because only 12% of waria stated that they consistently used condoms during any sex act, it is important to warn them that STD/HIV transmission can occur with either anal or oral sex and that the risk of either anal or oral transmission can be reduced by condom use. In addition, high rates of asymptomatic syphilis and rectal gonorrhoea warrant a periodic screening and treatment for these infections in this population. Because waria have the highest rates of HIV and their clients consist of homosexual and bisexual men, successful prevention efforts in waria could help curb the spread of the epidemic.

Adult↗

Differential of HIV prevalence in women and men who attended sexually transmitted disease clinics at HIV sentinel surveillance sites in Kenya, 1990-2001.

Several studies in sub-Saharan Africa have reported that HIV prevalence in young women is higher than in young men. We used data from Kenya HIV sentinel surveillance conducted from 1990 to 2001 among sexually transmitted disease (STD) patients (15-49 years old) to investigate consistency of gender differentials over time and their risk factors. Of the 15,889 STD patients, the HIV prevalence ranged from 16.0% in 1990 to 41.8% in 1997. The odds ratios (ORs) of HIV infection for women compared to men decreased by age; women 15-24 years were nearly twice as likely as men of the same ages to be HIV infected (OR 1.7 [1.5-2.0]), but risk in those >44 years was almost equal (OR 0.8 [95% CI 0.7-1.2]). The odds of HIV infection for women compared to men were twice in unmarried patients (OR 2.1 [95% CI 1.8-2.3]). This association persisted after controlling for age groups or marital status, residence, level of education, and presence of STD syndromes. This pattern had been consistent over 12 years. Adolescent women with symptoms of STDs should be a focus for the HIV/STD intervention programmes because of their high risk for HIV.

Adolescent↗

Perinatal hepatic infarction in twin-twin transfusion.

We report a case of a twin pregnancy which was complicated by a twin-twin transfusion in which the recipient twin was noted to have an intra-abdominal echogenic mass. This twin died at two days of age of hepatic infarction. The donor twin was healthy at birth, at thirty weeks' gestation, and did not have any subsequent problems. Fetal intra-abdominal echogenicity may be a marker of hepatic infarction.

Adult↗

Examination of a vehicle for use with water soluble materials in the murine local lymph node assay.

The murine local lymph node assay (LLNA) is a validated method for identifying skin sensitization hazard. Vehicle choice can influence the sensitization potential of haptens in both the LLNA and in humans, therefore selection of an appropriate vehicle is important. Suggested vehicles for the LLNA include organic solvents and organic-aqueous mixtures. However, due to its high surface tension and poor wetting qualities, water is not recommended and therefore testing aqueous soluble materials can be problematic. The aims of this investigation were to identify a water-based vehicle that possesses better skin wetting properties than water alone, and to assess its performance relative to other solvents in the LLNA using aqueous soluble haptens. The selected wetting agent was the surfactant Pluronic(R) L92 (L92). Concentrations of L92 of up to 50% did not induce positive responses in the LLNA. 1% aqueous L92 was chosen for further examination. Dose-response analyses were performed with dinitrobenzene sulfonic acid (DNBS) and formaldehyde formulated either in water, 1% L92, dimethyl sulfoxide (DMSO) or dimethyl formamide (DMF). Potassium dichromate (PDC) and nickel sulfate were tested in 1% L92, DMSO or DMF. The highest concentration of potassium dichromate was retested in each vehicle and in water to assess the effect of the wetting agent. Estimates of the relative sensitizing potency in each vehicle were determined by calculation of EC3 values (the estimated concentration required to induce a threshold positive response). While DNBS and formaldehyde produced positive responses in all four vehicles, their relative potency varied among the vehicles. The rank ordering of potencies for both materials was, from highest to lowest, DMF > or = DMSO > 1% L92 > water. Compared with water, use of 1% L92 resulted in >2-fold increase in potency for DNBS and >3-fold increase for formaldehyde. PDC was positive in DMF, DMSO and 1% L92. The potency ranking was DMF > or = DMSO > 1% L92. Re-evaluation of 0.5% PDC confirmed that formulations of both DMSO and DMF induced strong proliferative responses, whereas somewhat less proliferation was recorded with the 1% L92 vehicle. PDC in water was without activity. The performance of 1% L92 as a vehicle for nickel sulfate was assessed relative to DMSO and DMF. In DMSO, nickel sulfate produced a stimulation index (SI) >3 at only the highest level. Testing in DMF induced low levels of proliferation, but failed to produce a SI of 3 at any concentration tested. When formulated in 1% L92, nickel sulfate caused a SI of 3 when tested at 2.5%. Based on the results of these experiments, for identification of sensitization hazard of aqueous soluble materials using the LLNA, DMF and DMSO are the preferred vehicles. However, if a test material is not soluble in DMF or DMSO, or if higher test concentrations can be achieved in an aqueous vehicle, then 1% L92 may provide a better alternative to water alone in terms of improved assay performance.

Allergens↗

A skin sensitization safety assessment of a new bleach activator technology in detergent applications.

A new chemical called nonanoyl amido caproylacid oxybenzenesulphonate (NACAOBS) is being developed for use as a bleach activator in laundry detergents. Bleach activators, like NACAOBS, are typically used at levels between 2% and 6% in laundry detergents. NACAOBS is stable in aqueous solutions, but undergoes rapid perhydrolysis when combined with water and peroxygen bleach in laundry detergents. Animal testing demonstrated that NACAOBS, as a raw material, is a weak skin sensitizer. Clinical testing, including extended simulated laundry pretreatment, human repeat insult patch testing and home use testing was then undertaken, following sufficient reassurance of 1) the weak sensitization potential of the substance, 2) its rapid degradation in laundry wash solutions and, consequently, 3) low-to-negligible consumer dermal exposures to the native substance. Results confirmed the skin sensitization safety profile of laundry detergents containing NACAOBS, namely the absence of any reaction suggestive of contact sensitization (even under exaggerated dermal exposure conditions in a detergent matrix), and a skin compatibility profile comparable to that of current detergents. Further confirmation of the skin safety profile was obtained from a successful 12-month market test of a granular detergent containing 3.6% of the new substance, during which not a single adverse skin reaction was reported. In addition, NOBS (an oxybenzenesulphonate structural analogue to NACAOBS) has similar toxicological properties and has been safely marketed in detergents at similar levels for many years. It can be concluded that the likelihood of NACAOBS to induce skin sensitization or even elicit allergic reactions in consumer detergent use scenarios is negligible.

Animals↗

The local lymph node assay: past, present and future.

The local lymph node assay (LLNA) was developed originally as a method for the identification of chemicals that have the potential to cause skin sensitization and allergic contact dermatitis. The assay is based on an understanding that the acquisition of contact sensitization is associated with, and dependent upon, the stimulation by chemical allergens of lymphocyte proliferative responses in skin-draining lymph nodes. Those chemicals that provoke a defined level of lymph node cell (LNC) proliferation (a 3-fold or greater increase compared with concurrent vehicle controls) are classified as skin sensitizers. Following its original inception and development, the LLNA was the subject of both national and international interlaboratory collaborative trials, and of very detailed comparisons with other test methods and with human skin sensitization data. The assay has now been validated fully as a stand-alone test for the purposes of hazard identification. In recent years, there has been a growing interest also in the use of the LLNA to assess the potency of contact allergens and in risk assessment. There is reason to believe that the extent of skin sensitization achieved is associated with the vigour of LNC proliferation induced in draining nodes. Given this relationship, the relative potency of skin sensitizing chemicals is measured in the LLNA by derivation of an EC3 value, this being the concentration of chemical required to provoke a 3-fold increase in the proliferation of LNC compared with controls. Experience to date indicates that relative potency as determined using this approach correlates closely with what is known of the activity of skin sensitizing chemicals in humans. In this article, we review the development, evaluation and validation of the LLNA for the purposes of hazard identification, and the more recent application of the method for evaluation of potency in the context of risk assessment. In addition, we consider what new applications and modifications are currently being investigated.

Allergens↗

The feasibility of integrated STI prevalence and behaviour surveys in developing countries.

BACKGROUND: In countries where STI/HIV prevalence data and behavioural data are scarce UNAIDS second generation HIV surveillance guidelines recommend measuring STI/HIV prevalence and risk behaviours in vulnerable populations but do not recommend conducting these surveys concurrently because of concerns about participation rates, cost, and provision of services. OBJECTIVES: To assess the feasibility of conducting a national combined STD prevalence and behaviour survey in Mali among vulnerable populations with the intention of institutionalisation. METHODS: From March to June 2000 an integrated STI prevalence and behaviour survey was conducted using cluster sampling among five risk groups in four sites in Mali, west Africa. 2229 individuals in non-traditional settings such as taxi/bus stations, market areas, households, and brothels participated in any one or all components of the study: (1) behavioural questionnaire, (2) urine sample for Neisseria gonorrhoeae (GC)/Chlamydia trachomatis (CT) testing, (3) a fingerstick drop of blood for syphilis, and/or (4) HIV testing. RESULTS: High participation rates of 84%-100% were achieved despite specimen collection and HIV testing. Rates fell only slightly when participants were asked to provide biological samples and participants were more likely to provide urine than blood. Rates among the different groups for HIV and syphilis testing are similar and suggest that refusal was most probably because of a reluctance to give blood rather than because of HIV testing. The cost of the biological component added approximately $30 per participant. Included in the $30 are the costs of training, participant services, laboratory personnel and supplies, STI drugs, and STI testing costs. The total cost of the survey was $154,905. Biomarkers aided in validation of answers to behavioural questions. Consenting individuals received HIV pretest and post-test counselling and referral to a trained health provider for treatment of STI and the provision of services provided the framework for interventions in the groups following the survey. CONCLUSION: This represents an effective methodology for collecting risk behaviour and STI/HIV prevalence information concurrently and should be considered by countries expanding STI/HIV surveillance as part of UNAIDS second generation HIV surveillance.

Automobile Driving↗