Antibody Prevalence in Epilepsy before Surgery (APES) in drug-resistant focal epilepsy.

OBJECTIVE: There is a growing recognition of immune-mediated causes in patients with focal drug-resistant epilepsy (DRE); however, they are not systematically assessed in the pre-surgical diagnostic workup. Early diagnosis and initiation of immunotherapy is associated with a favorable outcome in immune-mediated seizures. Patients with refractory focal epilepsy with neuronal antibodies (Abs) tend to have a worse surgical prognosis when compared to other etiologies. METHODS: We studied the prevalence of serum Abs in patients ≥18 years of age with DRE of unknown cause before surgery. We proposed and calculated a clinical APES (Antibody Prevalence in Epilepsy before Surgery) score for each subject, which was modified based on Dubey's previously published APE2 score. RESULTS`: A total of 335 patients were screened and 86 subjects were included in final analysis. The mean age at the time of recruitment was 44.84 ± 14.86 years, with age at seizure onset 30.89 ± 19.88 years. There were no significant differences among baseline clinical features between retrospective and prospective sub-cohorts. The prevalence of at least one positive Ab was 33.72%, and central nervous system (CNS)-specific Abs was 8.14%. APES score ≥4 showed slightly better overall prediction (area under the curve [AUC]: 0.84 vs 0.74) and higher sensitivity (100% vs 71.4%), with slightly lower but similar specificity (44.3% vs 49.4%), when compared to APE2 score ≥4. For subjects who had available positron emission tomography (PET) results and all components of APES score (n = 60), the sensitivity of APES score ≥4 yielded a similar prediction potential with an AUC of 0.80. SIGNIFICANCE: Our findings provide persuasive evidence that a subset of patients with focal DRE have potentially immune-mediated causes. We propose an APES score to help identify patients who may benefit from a workup for immune etiologies during the pre-surgical evaluation for focal refractory epilepsy with unknown cause.

Pharmacokinetics and efficacy of atropine sulfate/obidoxime chloride co-formulation against VX in a guinea pig model.

Nerve agent exposure is generally treated by an antidote formulation composed of a muscarinic antagonist, atropine sulfate (ATR), and a reactivator of acetylcholinesterase (AChE) such as pralidoxime, obidoxime (OBI), methoxime, trimedoxime or HI-6 and an anticonvulsant. Organophosphates (OPs) irreversibly inhibit AChE, the enzyme responsible for termination of acetylcholine signal transduction. Inhibition of AChE leads to overstimulation of the central and peripheral nervous system with convulsive seizures, respiratory distress and death as result. The present study evaluated the efficacy and pharmacokinetics (PK) of ATR/OBI following exposure to two different VX dose levels. The PK of ATR and OBI administered either as a single drug, combined treatment but separately injected, or administered as the ATR/OBI co-formulation, was determined in plasma of naïve guinea pigs and found to be similar for all formulations. Following subcutaneous VX exposure, ATR/OBI-treated animals showed significant improvement in survival rate and progression of clinical signs compared to untreated animals. Moreover, AChE activity after VX exposure in both blood and brain tissue was significantly higher in ATR/OBI-treated animals compared to vehicle-treated control. In conclusion, ATR/OBI has been proven to be efficacious against exposure to VX and there were no PK interactions between ATR and OBI when administered as a co-formulation.

RETRACTED: Proof of concept efficacy study of intranasal stabilized isoamyl nitrite (SIAN) in rhesus monkeys against acute cyanide poisoning.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editors-in-Chief as the authors were unable to provide documentation of approval for the interinstitutional assurance /vertebrate animal section of the paper by the relevant authority, Public Health Service (PHS) Office of Laboratory Animal Welfare (OLAW) in the time that was provided.

Retraction notice to "Proof of concept efficacy study of intranasal stabilized isoamyl nitrite (SIAN) in Rhesus monkeys against acute cyanide poisoning" [Regul. Toxicol. Pharmacol. 123 (2021) 104927].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editors-in-Chief as the authors were unable to provide documentation of approval for the interinstitutional assurance/vertebrate animal section of the paper by the relevant authority, Public Health Service (PHS) Office of Laboratory Animal Welfare (OLAW) in the time that was provided.

Educational value of the transplant experience in urology residency.

INTRODUCTION To evaluate the educational value of transplant rotation in urology residency. In the United States, exposure to kidney transplantation during urology residency has declined significantly over the past few decades. At our institution, transplantation has been a core component of urology residency since its inception in 1959. MATERIALS AND METHODS: A 15-question anonymous survey was developed. The first 8 questions queried demographics and the last 7 were a set of questions with a Likert Scale response. The survey was electronic- mailed to past and current urology residents who had completed the transplant rotation, dating back to 1972. RESULTS: A total of 61 out of 98 (62%) individuals responded. The majority (59%) were general urologists, and one (2%) had completed a transplant fellowship. In their practices, 17% performed kidney transplants and 28% performed donor nephrectomies. Overall, 100% responded that the skills learned on the transplant rotation were beneficial for urology training, 100% had learned valuable vascular surgical techniques, and 93% felt that urology residents should have clinical transplant experience during their training. There was no statistical difference between the younger and older graduates in Likert scale responses. CONCLUSION: The majority of graduates did not perform transplants in their practice, yet, all of responders agreed that the skills learned on the transplant rotation were beneficial and 93% expressed that urology residents should have clinical transplant experience during residency. Kidney transplantation should be an integral part of urology residency training.

Sensor and Sensor Fusion Technology in Autonomous Vehicles: A Review.

With the significant advancement of sensor and communication technology and the reliable application of obstacle detection techniques and algorithms, automated driving is becoming a pivotal technology that can revolutionize the future of transportation and mobility. Sensors are fundamental to the perception of vehicle surroundings in an automated driving system, and the use and performance of multiple integrated sensors can directly determine the safety and feasibility of automated driving vehicles. Sensor calibration is the foundation block of any autonomous system and its constituent sensors and must be performed correctly before sensor fusion and obstacle detection processes may be implemented. This paper evaluates the capabilities and the technical performance of sensors which are commonly employed in autonomous vehicles, primarily focusing on a large selection of vision cameras, LiDAR sensors, and radar sensors and the various conditions in which such sensors may operate in practice. We present an overview of the three primary categories of sensor calibration and review existing open-source calibration packages for multi-sensor calibration and their compatibility with numerous commercial sensors. We also summarize the three main approaches to sensor fusion and review current state-of-the-art multi-sensor fusion techniques and algorithms for object detection in autonomous driving applications. The current paper, therefore, provides an end-to-end review of the hardware and software methods required for sensor fusion object detection. We conclude by highlighting some of the challenges in the sensor fusion field and propose possible future research directions for automated driving systems.

Benign breast papilloma: Is surgical excision necessary?

In many centers internationally, current standard of care is to excise all papillomas of the breast, despite recently reported low rates of upgrade to malignancy on final excision. The objective of this study was to determine the upgrade rate to malignancy in patients with papilloma without atypia. A retrospective review of a prospectively maintained database of all cases of benign intraductal papilloma in a tertiary referral symptomatic breast unit between July 2008 and July 2018 was performed. Patients with evidence of malignancy or atypia on core biopsy and those with a history of breast cancer or genetic mutations predisposing to breast cancer were excluded. One hundred and seventy-three cases of benign papilloma diagnosed on core biopsy were identified. Following exclusions, the final cohort comprised of 138 patients. Mean age at presentation was 51. Mean follow-up time was 9.6 months. The most common symptom was a lump (40%). Of the 124 patients who underwent excision, three had ductal carcinoma in situ and there were no cases of invasive disease, giving an upgrade rate to malignancy of 2.4%. Upgrade to other high-risk lesions (atypical lobular and ductal hyperplasia and lobular carcinoma in situ) was demonstrated in 15 cases (12.1%). Benign papilloma was confirmed in 100 cases (81.5%), and 6 (4.8%) had no residual papilloma found on final excision. Twelve patients (8.7%) were managed conservatively. Of those, one later went on to develop malignancy. Patients with a diagnosis of benign papilloma without atypia on core biopsy have a low risk of upgrade to malignancy on final pathology, suggesting that observation may be a safe alternative to surgical excision. Further research is warranted to determine which patients can be safely managed conservatively.

Lobular intraepithelial neoplasia: Outcomes and optimal management.

INTRODUCTION: Lobular neoplasia is a term encompassing both atypical lobular hyperplasia and lobular carcinoma in situ. These pathological findings are of uncertain malignant potential and predispose to a higher lifetime risk of breast cancer. Debate surrounds the management of such lesions, with the rationale for diagnostic excision based on the possibility of upgrading to malignancy. In this study, we report the upgrade rate of these lesions and risk of subsequent development of breast cancer. METHODS: This is a retrospective review of a prospectively maintained data base of all biopsies of breast screening-detected abnormalities in a single Irish breast-screening unit. We included all patients with lobular neoplasia on core needle biopsy who underwent diagnostic excision from 2005 to 2012. We excluded those who had concurrent high-risk lesions on biopsy. End points included upgrade rate and subsequent diagnosis of malignancy on follow-up. RESULTS: During the study period, 66 patients met criteria for inclusion, with a mean age of 53.74 years. Upgrade rate following excision was 13.64% (n = 9/66). Of those not upgraded, 7.02% (n = 4/57) were subsequently diagnosed with malignancy. Median time to diagnosis was 59.61 months (range = 10.5-124.4). CONCLUSION: There is a significant rate of upgrade following diagnostic excision of lobular neoplasia, supporting the practice of diagnostic excision. There is an increased lifetime risk of breast cancer for women with a diagnosis of lobular neoplasia, with many of these cancers occurring outside the standard five-year monitoring period, suggesting a potential benefit in extending surveillance.

Short communication: Effect of feeding pooled and nonpooled high-quality colostrum on passive transfer of immunity, morbidity, and mortality in dairy calves.

Pooling colostrum is commonly practiced on Irish dairy farms. Pooling can result in dilution when colostrums with high and low IgG concentrations are mixed, thereby predisposing calves to failure of passive immunity. The objectives of this study were to compare IgG concentrations in colostrum from individual cows with colostrum pooled from several cows, and assess serum IgG concentrations, morbidity, and mortality among calves fed colostrum from their own dam, from a different cow, or pooled from several cows. We hypothesized that pooling colostrum reduces IgG concentration due to dilution compared with colostrum from individual cows, and that calves fed pooled colostrum achieve lower serum IgG concentrations than calves fed colostrum from individual cows. Calves were randomly assigned to 1 of 3 groups: (1) fed colostrum from their own dam (n = 20); (2) fed colostrum from a different dam (n = 20); or (3) fed pooled colostrum (n = 18). A sample of colostrum fed to each calf was collected. Serum samples were collected from calves at birth (0 h) and at 24 h after colostrum feeding. Colostrum and serum IgG concentrations were measured by radial immunodiffusion. Calves were weighed at birth and at weaning, and the health status of each calf was assessed twice daily. Health assessment was based on general demeanor, rectal temperature, fecal consistency, respiratory rate, and the presence of cough, nasal, or ocular discharge. Colostrum and serum IgG concentrations, and weaning weights were compared using ANOVA. Associations between group and morbidity or mortality rates were compared using χ2 or Fisher's exact tests. Median and 95% confidence intervals (95% CI) of IgG concentrations of colostrum were 99.4 (81.8-111.5), 95.2 (84.1-107.2), and 100.7 (90.5-104.4) g/L for own dam, different dam, and pooled groups, respectively. We did not find any differences in colostrum IgG concentrations among the colostrum sources. Median (95% CI) serum IgG concentrations at 24 h were 52.0 (45.6-65.9), 55.7 (51.2-65.9), and 53.1 (46.2-63.7) g/L for calves that received colostrum from own dam, different dam, and pooled, respectively. All calves achieved adequate passive immunity. Serum IgG concentrations at 24 h, weaning weights, and proportions of morbidity and mortality were not different among the 3 groups. Our results suggest that on dairy farms where median colostrum IgG concentrations are high and colostrum management is optimal, pooling has a minimal effect on passive immunity and subsequent calf health.

Optical magnetic detection of single-neuron action potentials using quantum defects in diamond.

Magnetic fields from neuronal action potentials (APs) pass largely unperturbed through biological tissue, allowing magnetic measurements of AP dynamics to be performed extracellularly or even outside intact organisms. To date, however, magnetic techniques for sensing neuronal activity have either operated at the macroscale with coarse spatial and/or temporal resolution-e.g., magnetic resonance imaging methods and magnetoencephalography-or been restricted to biophysics studies of excised neurons probed with cryogenic or bulky detectors that do not provide single-neuron spatial resolution and are not scalable to functional networks or intact organisms. Here, we show that AP magnetic sensing can be realized with both single-neuron sensitivity and intact organism applicability using optically probed nitrogen-vacancy (NV) quantum defects in diamond, operated under ambient conditions and with the NV diamond sensor in close proximity (∼10 µm) to the biological sample. We demonstrate this method for excised single neurons from marine worm and squid, and then exterior to intact, optically opaque marine worms for extended periods and with no observed adverse effect on the animal. NV diamond magnetometry is noninvasive and label-free and does not cause photodamage. The method provides precise measurement of AP waveforms from individual neurons, as well as magnetic field correlates of the AP conduction velocity, and directly determines the AP propagation direction through the inherent sensitivity of NVs to the associated AP magnetic field vector.

'I didn't want to pass that on to my child, being afraid to go to the dentist': making sense of oral health through narratives of connectedness over the life course.

While previous sociological research on oral health has identified the relevance of personal relationships, there is more scope to analyse the mouth through a lens of connectedness. Recent qualitative interviews with 43 older people (65+) in England and Scotland found that participants constructed relational narratives to make sense of their oral health practices. By drawing on ideas of family practices, family display and personal life, we illustrate how the mouth can be understood relationally. Participants presented their own embodied experiences as connected to the actions of their parents. Narratives also reflected how, as parents and grandparents themselves, participants tried to shape the experiences of others. In this way, oral health practices were conceptualised as being about family. This can be seen in self-narratives that demonstrated how participants located themselves as embedded in webs of ongoing relationships. We highlight the importance of narrated practices of thinking and feeling, whereby participants imagined doing oral health, and indeed family, in different ways. We thereby demonstrate how oral health practices are constituted through family connectedness and at the same time how these practices contribute to the constitution of family. Policy should therefore pay attention to family relations when promoting improvements in oral health practices.

Short communication: Use of a digital refractometer in assessing immunoglobulin G concentrations in colostrum and the first 5 transition milkings in an Irish dairy herd.

Transition milk is a source of immunoglobulin G (IgG) and could potentially be used to provide calves with passive immunity, when the IgG concentration is ≥50 g/L. Assessment of IgG concentrations in transition milk would be required before feeding and could be conducted using cow-side tests such as refractometers. Currently, limited information is available on the ability of refractometers to assess transition milk quality. We hypothesized that digital refractometry could be used to provide an accurate cow-side assessment of IgG concentrations in colostrum and transition milk, and IgG concentration in colostrum and one or more transition milking in an Irish herd is >50 g/L. The objectives of this study were to determine the IgG concentrations in colostrum and first, second, third, fourth, and fifth transition milk, and determine the utility of a digital refractometer in assessing quality of colostrum and transition milk produced by cows in a pasture-based dairy production system. A convenient sample of 75 dairy cows were enrolled. Colostrum and transition milk IgG concentrations were determined by radial immunodiffusion and refractometry. Sensitivity and specificity of the refractometer were determined and cut-off points that maximized sensitivity and specificity were determined using receiver operating characteristic curves. Median (range) IgG concentrations in colostrum and first, second, third, fourth, and fifth milking were 99.6, 43.5, 12.5, 5.3, 1.9, and 1.8 g/L, respectively. The sensitivity (0.8-1) of digital refractometry in identifying samples with low IgG concentrations in colostrum, first, second, and third transition milk was acceptable. In contrast, digital refractometry was not useful for assessing IgG concentrations in the fourth and fifth milking due to low IgG concentrations.

Socioeconomic Inequalities in Adolescent Substance Use: Evidence From Twenty-Four European Countries.

BACKGROUND: While there is evidence for socioeconomic inequalities in some adolescent substance use behaviors, there is limited information on how socioeconomic inequalities compare across European countries and over time. OBJECTIVES: To compare socioeconomic inequalities in problematic adolescent substance use (regular smoking, heavy episodic drinking, and cannabis use) across 24 European countries at two time points. METHODS: We use the European School Survey Project on Alcohol and Other Drugs (ESPAD) to examine socioeconomic inequalities in problematic adolescent substance use across 24 European countries in 2007 (n = 73,877) and 2011 (n = 71,060) using within country logistic regressions. Socioeconomic inequalities are measured using a relative index of inequality based on highest level of parental education relative to country of residence within survey year. Countries are ranked according to socioeconomic differentials. RESULTS: In 2007, lower socioeconomic status (SES) adolescents had significantly higher odds of heavy episodic drinking in 10 countries, regular smoking in 12 countries, and recent cannabis use in 1 country. In 2011, the number of countries were 11, 15, and 0, respectively. In 2007, lower SES adolescents had a significantly lower odds of heavy episodic drinking in one country, regular smoking in one country, and cannabis use in four countries. In 2011, the number of countries were two, one, and six, respectively. There was little evidence for changes in socioeconomic inequalities over time. CONCLUSIONS: There are large country level differences in socioeconomic inequalities in adolescent substance use.

Impact of center volume and the adoption of laparoscopic donor nephrectomy on outcomes in pediatric kidney transplantation.

Reports for pediatric kidney transplant recipients suggested better outcomes for ODN compared to LDN. Contemporary outcomes stratified by donor type and center volume have not been evaluated in a national dataset. UNOS data (2000-2014) were analyzed for pediatric living donor kidney transplant recipients. The primary outcome was GF; secondary outcomes were DGF, rejection, and patient survival. Live donor nephrectomies for pediatric recipients decreased 30% and transitioned from ODN to LDN. GF rates did not differ for ODN vs LDN (P = .24). GF was lowest at high volume centers (P < .01). Donor operative approach did not contribute to GF. LDN was associated with less rejection than ODN (OR 0.66, CI 0.5-0.87, P < .01). Analysis of the 0- to 5-yr recipient group showed no effect of ODN vs LDN on GF or rejection. For the contemporary era, there was no association between DGF and LDN in the 0- to 5-yr group (OR 1.12, CI 0.67-1.89, P = .67). Outcomes of kidney transplants in pediatric recipients following LDN have improved since its introduction and LDN should be the approach for live donor nephrectomy regardless of recipient age. The association between case volume and improved outcomes highlights future challenges in organ transplantation.

Gender differences in preferences for psychological treatment, coping strategies, and triggers to help-seeking.

OBJECTIVE: There is some evidence that men and women deal with stress in different ways; for example, a meta-analysis found that women prefer to focus on emotions as a coping strategy more than men do. However, sex differences in preferences for therapy is a subject little explored. DESIGN: A cross-sectional online survey. METHOD: Participants (115 men and 232 women) were recruited via relevant websites and social media. The survey described therapies and asked participants how much they liked each. Their coping strategies and help-seeking behaviour were assessed too. RESULTS: Survey data were analysed using multiple linear regression. After familywise adjustment of the alpha for multiple testing to p < .0125, and controlling for other relevant variables, men liked support groups more than women did (ß = -.163, p < .010), used sex or pornography to cope with stress more than women did (Exp[B] = .280, p < .0002), and thought that there is a lack of male-friendly options more than women did (Exp[B] = .264, p < .002). The majority of participants expressed no preference for the sex of their therapist, but of those who did, men were only slightly more likely to prefer a female therapist whereas women were much more likely to prefer females (p < .0004). Even after familywise adjustment, there were still more significant findings than would be expected by chance (p < .001, two-tailed). CONCLUSIONS: Although there are many similarities in the preferences of men and women regarding therapy, our findings support the hypothesis that men and women show statistically significant differences of relevance to clinical psychologists. PRACTITIONER POINTS: Men are less inclined than women to seek help for psychological issues This study demonstrates that men and women show significant differences in some aspects of therapy, coping behaviour, and help-seeking It is possible that men would be more inclined to seek help if therapies catered more for men's preferences Practitioners can learn to improve the success of their practice by taking the gender of clients into account.

A partial hominoid innominate from the Miocene of Pakistan: description and preliminary analyses.

We describe a partial innominate, YGSP 41216, from a 12.3 Ma locality in the Siwalik Group of the Potwar Plateau in Pakistan, assigned to the Middle Miocene ape species Sivapithecus indicus. We investigate the implications of its morphology for reconstructing positional behavior of this ape. Postcranial anatomy of extant catarrhines falls into two distinct groups, particularly for torso shape. To an extent this reflects different although variable and overlapping positional repertoires: pronograde quadrupedalism for cercopithecoids and orthogrady for hominoids. The YGSP innominate (hipbone) is from a primate with a narrow torso, resembling most extant monkeys and differing from the broader torsos of extant apes. Other postcranial material of S. indicus and its younger and similar congener Sivapithecus sivalensis also supports reconstruction of a hominoid with a positional repertoire more similar to the pronograde quadrupedal patterns of most monkeys than to the orthograde patterns of apes. However, Sivapithecus postcranial morphology differs in many details from any extant species. We reconstruct a slow-moving, deliberate, arboreal animal, primarily traveling above supports but also frequently engaging in antipronograde behaviors. There are no obvious synapomorphic postcranial features shared exclusively with any extant crown hominid, including Pongo.