The impact of COVID-19 on O&G trainees; where are we now?

Background and Objectives: Obstetrics and Gynaecology (O&G) training continues to face challenges caused by the COVID-19 pandemic, particularly in gynaecological surgical training. This follow-up survey captures the ongoing effect on O&G trainees and highlights the future recovery plan considering the historical training gaps in benign gynaecology. Materials and Methods: an anonymised survey was emailed to all O&G trainees in Kent, Surrey and Sussex (KSS). Responses were collected over 6 weeks. Main Outcome Measures and Results: 53% of trainees responded. In total, 78% of trainees agreed that the pandemic had an ongoing negative effect on their physical and mental wellbeing respectively. Trainees felt the prior negative impact on obstetric training is improving, whilst 88% still experience a negative impact on their gynaecology surgical training despite the resumption of elective services in the National Health Service (NHS). 80% continue to feel the negative impact on their educational activities and 88% felt their overall training continues to be negatively impacted. 70% were positive that they would recover from this. Responses were representative of each training year. Interestingly, 95% of trainees had accepted the COVID vaccine. Conclusion: despite "restoration" of normal services, the negative impact on trainees particularly benign gynaecology surgical training continues. Addressing pre-pandemic training gaps whilst tackling the surgical back-log and the needs of service provision will continue for years to follow. What is new?: Future training needs to incorporate creative ways of acquiring surgical skills. It is imperative to imbed simulation training into O&G training programmes. Pastoral support is key to ensure trainees' mental and physical well-being are prioritised and the already high burn-out rates do not worsen.

Body temperature of free-ranging koalas (Phascolarctos cinereus) in south-east Queensland.

The distribution of the koala (Phascolarctos cinereus) in Queensland is predicted to contract as a result of climate change, driven by the frequency, intensity and duration of heatwaves and drought. However, little is known about the physiological responses of this species to environmental extremes under field conditions. This study aimed to establish the efficacy of surgically implanted thermal radio transmitters and data loggers to measure the body temperature of free-ranging koalas across a range of environmental conditions and ambient temperatures. Five free-ranging koalas in southeast Queensland were implanted with thermal transmitters and data loggers waxed together as a single package. Body temperatures were recorded for variable periods ranging from 3 to 12 months. Diurnal rhythms in body temperature were detected irrespective of season. The long-term diurnal body temperature peak for all koalas occurred between 16:00 and 17:00 h and body temperature was 36.7-36.9 °C, the long-term nadir occurred between 07:00 and 08:00 h and body temperature was 35.4-35.7 °C. Koala body temperatures as low as 34.2 °C and as high as 39.0 °C were recorded. Thermolability became apparent when ambient temperatures were outside the deduced thermal neutral zone for koalas (14.5-24.5 °C): heat was accumulated during the day and dissipated during the cool of the night. While this study is the first to report on body temperature of free-ranging koalas in their normal behavioural context, further investigations are necessary to determine the physiological boundaries of the thermal niche for this species, in order to better equip models that will more accurately predict the impacts of climate change on koalas.

Recording body temperature in koalas (Phascolarctos cinereus): a comparison of techniques.

OBJECTIVE: Compare the use of four techniques to measure body temperature in koalas: intraperitoneal (thermal data logger and temperature sensitive radio transmitter), rectal (certified thermometer), tympanic (infrared thermometer), and hind foot (infrared camera). METHODS: The body temperature data collected concurrently from the intraperitoneal loggers were used as the benchmark in the analyses. RESULTS: The rectal, foot and tympanic methods consistently recorded lower body temperature when compared with the benchmark. There was a strong positive relationship (R2 = 0.79) between logger and rectal measurements, but no significant relationship between logger and foot or logger and tympanic measurements. CONCLUSION: Rectal measurements can be used to record internal body temperature, with the caveat that such measurements will generally register a temperature approximately 0.25°C lower than the actual intraperitoneal temperature.

Cortical abnormalities in bipolar disorder: an MRI analysis of 6503 individuals from the ENIGMA Bipolar Disorder Working Group.

Despite decades of research, the pathophysiology of bipolar disorder (BD) is still not well understood. Structural brain differences have been associated with BD, but results from neuroimaging studies have been inconsistent. To address this, we performed the largest study to date of cortical gray matter thickness and surface area measures from brain magnetic resonance imaging scans of 6503 individuals including 1837 unrelated adults with BD and 2582 unrelated healthy controls for group differences while also examining the effects of commonly prescribed medications, age of illness onset, history of psychosis, mood state, age and sex differences on cortical regions. In BD, cortical gray matter was thinner in frontal, temporal and parietal regions of both brain hemispheres. BD had the strongest effects on left pars opercularis (Cohen's d=-0.293; P=1.71 × 10-21), left fusiform gyrus (d=-0.288; P=8.25 × 10-21) and left rostral middle frontal cortex (d=-0.276; P=2.99 × 10-19). Longer duration of illness (after accounting for age at the time of scanning) was associated with reduced cortical thickness in frontal, medial parietal and occipital regions. We found that several commonly prescribed medications, including lithium, antiepileptic and antipsychotic treatment showed significant associations with cortical thickness and surface area, even after accounting for patients who received multiple medications. We found evidence of reduced cortical surface area associated with a history of psychosis but no associations with mood state at the time of scanning. Our analysis revealed previously undetected associations and provides an extensive analysis of potential confounding variables in neuroimaging studies of BD.

Prefrontal cortical thinning links to negative symptoms in schizophrenia via the ENIGMA consortium.

BACKGROUND: Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity. METHODS: This study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores). RESULTS: Meta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (ß std = -0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged. CONCLUSIONS: Using an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.

INVESTIGATION OF ENROFLOXACIN-ASSOCIATED RETINAL TOXICITY IN NONDOMESTIC FELIDS.

Enrofloxacin is known to cause retinal toxicity in domestic cats. The hallmark lesion of enrofloxacin-associated retinal toxicity in domestic cats is thinning of the outer nuclear layer of the retina. Enrofloxacin is commonly used to treat bacterial infections in nondomestic felids because of its action against a wide spectrum of bacteria and the ability for it to be given orally. No previous studies have investigated the potential retinal toxicity of enrofloxacin in nondomestic felids. This retrospective study evaluated 81 eyes from 14 lions ( Panthera leo ) and 33 tigers ( Panthera tigris ) that had been enucleated or collected postmortem. The thickness of the outer nuclear retina was assessed in two separate sites in each eye by counting the rows of nuclei and by using digital image analysis software to determine the area of the nuclei at each site. Medical records were reviewed to determine the enrofloxacin dose for each cat. Cats that had not received enrofloxacin (n = 11) were compared with treated animals (n = 36). The outer nuclear layer thickness or area in treated versus untreated cats was not significantly different. Additionally, no clinical blindness was reported in any of the cats. This study showed no evidence of enrofloxacin-associated thinning of the outer nuclear layer in the lions and tigers evaluated, suggesting that enrofloxacin can be used safely in these animals.

Positive symptoms associate with cortical thinning in the superior temporal gyrus via the ENIGMA Schizophrenia consortium.

OBJECTIVE: Based on the role of the superior temporal gyrus (STG) in auditory processing, language comprehension and self-monitoring, this study aimed to investigate the relationship between STG cortical thickness and positive symptom severity in schizophrenia. METHOD: This prospective meta-analysis includes data from 1987 individuals with schizophrenia collected at seventeen centres around the world that contribute to the ENIGMA Schizophrenia Working Group. STG thickness measures were extracted from T1-weighted brain scans using FreeSurfer. The study performed a meta-analysis of effect sizes across sites generated by a model predicting left or right STG thickness with a positive symptom severity score (harmonized SAPS or PANSS-positive scores), while controlling for age, sex and site. Secondary models investigated relationships between antipsychotic medication, duration of illness, overall illness severity, handedness and STG thickness. RESULTS: Positive symptom severity was negatively related to STG thickness in both hemispheres (left: ßstd = -0.052; P = 0.021; right: ßstd = -0.073; P = 0.001) when statistically controlling for age, sex and site. This effect remained stable in models including duration of illness, antipsychotic medication or handedness. CONCLUSION: Our findings further underline the important role of the STG in hallmark symptoms in schizophrenia. These findings can assist in advancing insight into symptom-relevant pathophysiological mechanisms in schizophrenia.

Thermoregulation of the bovine scrotum 1: measurements of free-range animals in a paddock and pen.

The bull's scrotum and scrotal cord vasculature has traditionally been regarded as a thermoregulatory device for maintaining optimal testicular temperature for normal spermatogenesis. This assumption has mostly been derived from discrete measurements using thermocouples with limited data correlating continuous scrotal temperature (ST) to body temperature (BT). From mid-summer to early autumn, four Wagyu bulls (9-18 months) were surgically implanted with two data loggers (DL) logging at 30 min intervals: one on the right hand side flank and the other was attached to the visceral vaginal tunic of the mid-testis. Bulls were firstly housed in a paddock (PK) for 13 days and then moved to individual pens (IP), again for 13 days. Repeated measures analysis modelled the long-term and diurnal trends in BT and ST. While both day and time of day (TOD) were significant effects for ST at both housing locations (P < 0.005), only TOD showed significance for BT at both locations (P < 0.0001). Significant effects were seen between bulls with ST (F = 167.2, P < 0.001) but not BT (F = 0.03, P = 0.863), suggestive of variation in individual bull thermoregulatory capacity. Dual peaks were observed in ST at 0500 and 2130 h when housed in PK but not IP, suggesting ST may be influenced by external stimuli such as postural or behavioural changes. Reporting concurrent and continuous BT and ST will allow further investigation into factors influencing bovine ST and should be useful in selecting bulls with high degrees of thermoregulation capacity.

Measurement of bovine body and scrotal temperature using implanted temperature sensitive radio transmitters, data loggers and infrared thermography.

Synchronous and continuous measurement of body (BT) and scrotal temperature (ST) without adverse welfare or behavioural interference is essential for understanding thermoregulation of the bull testis. This study compared three technologies for their efficacy for long-term measurement of the relationship between BT and ST by means of (1) temperature sensitive radio transmitters (RT), (2) data loggers (DL) and (3) infrared imaging (IRI). After an initial pilot study on two bulls to establish a surgical protocol, RTs and DLs were implanted into the flank and mid-scrotum of six Wagyu bulls for between 29 and 49 days. RT frequencies were scanned every 15 min, whilst DLs logged every 30 min. Infrared imaging of the body (flank) and scrotum of each bull was recorded hourly for one 24-h period and compared to RT and DL data. After a series of subsequent heat stress studies, bulls were castrated and testicular tissue samples processed for evidence of histopathology. Radio transmitters were less reliable than DLs; RTs lost >11 % of data, whilst 11 of the 12 DLs had 0 % data loss. IRI was only interpretable in 35.8 % of images recorded. Pearson correlations between DL and RT were strong for both BT (r > 0.94, P < 0.001) and ST (r > 0.80, P < 0.001). Surgery produced temporary minor inflammation and scrotal hematoma in two animals post-surgery. Whilst scar tissue was observed at all surgical sutured sites when bulls were castrated, there was no evidence of testicular adhesion and normal active spermatogenesis was observed in six of the eight implanted testicles. There was no significant correlation of IRI with either DL or RT. We conclude that DLs provided to be a reliable continuous source of data for synchronous measurement of BT and ST.

Surgical implantation of temperature-sensitive transmitters and data-loggers to record body temperature in koalas (Phascolarctos cinereus).

BACKGROUND: Under predicted climate change scenarios, koala distribution in Australia is expected to be adversely affected. Recent studies have attempted to identify suitable habitat, based on models of bioclimatic regions, but to more accurately reflect the thermal tolerance and behavioural adaptations of the various regional populations, the koala's response to periods of heat stress will need to be investigated at the individual animal level. OBJECTIVE: To explore the safety and suitability of temperature-sensitive intra-abdominal implants for monitoring core body temperature in the koala. METHODS: A temperature-sensitive radio transmitter and thermal iButton data-logger, waxed together as a package, were surgically implanted into the abdominal cavity of four captive koalas. In one animal the implant was tethered and in the other three, it was left free-floating. RESULTS: After 3 months, the implants were removed and all four koalas recovered without complications. The tethering of the package in the one koala resulted in minor inflammation and adhesion, so this practice was subsequently abandoned. The free-floating deployments were complication-free and revealed a diurnal body temperature rhythm, with daily ranges of 0.4-2.8°C. The minimum recorded body temperature was 34.2°C and the maximum was 37.7°C. The difference in the readings obtained from the transmitters and iButtons never exceeded 0.3°C. CONCLUSIONS: The suitability of the surgical approach was confirmed, from both the animal welfare and data collection points of view.

Comment on "Apatite 4He/3He and (U-Th)/He evidence for an ancient Grand Canyon".

Flowers and Farley (Reports, 21 December 2012, p. 1616; published online 29 November 2012) propose that the Grand Canyon is 70 million years old. Starkly contrasting models for the age of the Grand Canyon-70 versus 6 million years-can be reconciled by a shallow paleocanyon that was carved in the eastern Grand Canyon 25 to 15 million years ago (Ma), negating the proposed 70 Ma and 55 Ma paleocanyons. Cooling models and geologic data are most consistent with a 5 to 6 Ma age for western Grand Canyon and Marble Canyon.

Identification and functional characterization of p130Cas as a substrate of protein tyrosine phosphatase nonreceptor 14.

Protein tyrosine phosphatase nonreceptor type 14 (PTPN14) is frequently mutated in a variety of human cancers. However, the cell signaling pathways regulated by PTPN14 largely remain to be elucidated. Here, we identify a list of potential substrates of PTPN14 using a phospho-proteomic approach. We show that p130 Crk-associated substrate (p130Cas) is a direct substrate of PTPN14 and that PTPN14 specifically regulates p130Cas phosphorylation at tyrosine residue 128 (Y128) in colorectal cancer (CRC) cells. We engineered CRC cells homozygous for a p130Cas Y128F knock-in mutant and found that these cells exhibit significantly reduced migration and colony formation, impaired anchorage-independent growth, slower xenograft tumor growth in nude mice and have decreased phosphorylation of AKT. Furthermore, we demonstrate that SRC phosphorylates p130Cas Y128 and that CRC cell lines harboring high levels of pY128Cas are more sensitive to SRC family kinase inhibitor Dasatinib. These findings suggest that p130Cas Y128 phosphorylation may be exploited as a predictive marker for Dasatinib response in cancer patients. In aggregate, our studies reveal a novel signaling pathway that has an important role in colorectal tumorigenesis.

Solid organ injury grading in trauma: accuracy of grading by surgical residents.

The American Association for the Surgery of Trauma developed an Organ Injury Scale for management of patients with splenic, kidney, or liver injuries. Despite widespread use of the guidelines, the person who determines the injury grade varies among institutions. Our purpose was to determine the accuracy and interobserver agreement between surgical residents and a radiologist in grading solid organ injuries. We retrospectively reviewed patients with solid organ injuries from January 2009 to May 2010 and compared the grade of solid organ injuries by a single resident with grades by a single blinded radiologist using a paired t test, analysis of variance, or Kruskal-Wallis. Computed tomography scans of 58 patients with splenic injuries, 43 with liver injuries, and 16 with kidney injuries were reviewed. Average grades for splenic injuries were 2.5 and 2.4 (radiologist/resident); liver injuries, 2.6 and 2.1; and kidney injuries, 2.7 and 2.8. There were no significant differences in grading by the radiologist and resident for splenic and kidney injuries; however, equal values were only achieved in 43 and 38 per cent, respectively. There was a significant difference (average rating difference 0.54, P = 0.0002) in grading between the radiologist and resident for liver injuries with only 35 per cent having equal values and the radiologist grading on average 0.5 points higher than the resident. No demographic, injury, or outcome variables were significantly associated with interobserver variability (P > 0.05). Despite a significant difference for liver injury grading, interobserver agreement between residents and a single radiologist was low. Clinical implications and the impact on outcomes related to interobserver variations require further study.

Comparison of children with onset of juvenile dermatomyositis symptoms before or after their fifth birthday in a UK and Ireland juvenile dermatomyositis cohort study.

OBJECTIVE: To compare 2 groups of children with juvenile dermatomyositis (DM), those with onset of symptoms before their fifth birthday versus those whose disease begins either on or after their fifth birthday, and to assess whether age at onset is associated with differences in disease presentation, treatments received, or outcomes 2 years after diagnosis. METHODS: Data were analyzed on children recruited to a UK juvenile DM cohort study with a diagnosis of probable or definite juvenile DM and less than 12 months between diagnosis and recruitment. RESULTS: Fifty-five (35%) of 157 children had onset of symptoms before their fifth birthday. At diagnosis, cutaneous ulceration was found in 32.7% of the younger group versus 11.8% of the older group (P = 0.003). Facial or body swelling was reported more often in the younger group, whereas headaches, alopecia, and Raynaud's phenomenon were all more frequently reported in the older group. At followup 2 years later, there were no important differences in outcomes between the groups. More than 90% of patients in both groups received both methotrexate and steroids. Twenty-three percent of both groups remained on steroids 2 years after diagnosis. CONCLUSION: Our study showed that children with juvenile DM with disease onset at age <5 years are more likely to present with ulcerative skin disease and edema. There were no clinically significant differences in outcomes between the 2 groups.

A retrospective wound review of standard four-port laparoscopic cholecystectomy: is there need for single-port laparoscopic surgery?

BACKGROUND: This study was designed to assess the satisfaction or otherwise of a proportion of the U.K. population who have undergone standard four-port laparoscopic cholecystectomy within the past 18 months. The results should indicate whether there is potential demand for a new, improved approach to surgery. METHODS: Patients who underwent laparoscopic cholecystectomy between October 2008 and October 2009 in two geographically separated general hospitals were identified from hospital databases. Notes were reviewed to confirm the technique and lack of conversion to an open procedure. Those who had immediate complications were excluded. A telephone questionnaire was conducted to answer questions related to long-term cosmetic and general satisfaction of the current procedure. RESULTS: Of the patients surveyed, 93% were happy or extremely happy with the current procedure, 48% experienced some wound-related issues (pain, infection), and 65% of those were at the umbilicus (a possible reflection of location and retrieval site for gallbladder). Cosmesis was rated less important than hospital cleanliness and experience of the surgeon. CONCLUSIONS: Overall satisfaction was high with the existing technique. The high rate of umbilical wound problems is an issue that will not be eradicated by introduction of single-port laparoscopic surgery.

Measurement and correlates of ano-genital distance in healthy, newborn infants.

Ano-genital distance (AGD) is a sexually dimorphic trait that is a well established reproductive toxicity endpoint in animals. In male animals, a shortened AGD is associated with a variety of genital abnormalities including hypospadias and cryptorchidism. Consensus on the anatomical definition of AGD in humans remains to be established and few data exist on the determinants and normal variance in the general population. We implemented a standardized anthropometric protocol to measure AGD, ano-scrotal distance (ASD), and ano-fourchette distance (AFD) in 169 (82 male, 87 female) infants in the University of Washington newborn nursery in 2008. We collected data on the following characteristics: weight, length, and occipital head circumference, race and relevant gestational complications. Using linear regression modelling, we examined AGD/ASD/AFD for sexual dimorphism, normal population variance and predictors of the measurement in infants. The mean male and female AGD measurements were 52.0 mm (SD +/- 5.5) and 37.2 mm (SD +/- 3.7). The mean ASD and AFD were 23.0 mm (SD +/- 3.8) and 15.1 mm (SD +/- 2.9). Weight, length, occipital head circumference and gestational age were associated with AGD (p < 0.05). Weight and length were the most important correlates to AGD. We confirmed previous findings that AGD is a sexually dimorphic measurement that is most strongly predicted by infant weight. The application of this measurement to clinically relevant outcomes remains to be explored in further depth.

Dysautonomia in a six-year-old mule in the United States.

Equine dysautonomia, also known as equine grass sickness (EGS), is a well documented disease in several countries. To the authors' knowledge, EGS has not been reported previously in North America. This report describes EGS in a 6-year-old female mule in the USA. Failure initially to consider EGS resulted in a delayed diagnosis. EGS should be considered as a differential diagnosis and appropriate diagnostic tests performed in similar cases in North America.

Comment on "Age and evolution of the Grand Canyon revealed by U-Pb dating of water table-type speleothems".

Polyak et al. (Reports, 7 March 2008, p. 1377) reported speleothem data leading to their inference that the western Grand Canyon incised much earlier than previously thought. This contradicts several lines of published geological knowledge in the region, hinges upon unjustified hydrogeological assumptions, and is based on two anomalous data points for which we offer alternative explanations.

Accuracy of MR imaging of the knee in adolescents.

OBJECTIVE: A report in the orthopedics literature states that MR imaging for internal derangement of the knee has a lower accuracy in adolescents than in adults and may even provide spurious information that alters clinical management. This assertion has not been specifically addressed in the radiology literature. The purpose of our study was to determine the accuracy of MR imaging in adolescents with regard to injury of the cruciate ligaments and menisci. MATERIALS AND METHODS: A database search of our institution's records from January 1998 to July 2000 yielded 2140 MR examinations of the knee, all of which had been performed with a standard knee protocol on a 1.5-T magnet. Of these 2140 examinations, 156 included patients younger than 18 years. Fifty-nine of these patients underwent surgery, and the orthopedic surgeons' operative reports were used as the gold standard with which the MR imaging results were compared. Thirty-four boys and 25 girls who ranged in age from 11 to 17 years (mean age, 15 years) were examined. The clinical notes for the remaining 97 patients were evaluated for information about management and clinical improvement. RESULTS: The sensitivity and specificity values for MR imaging of the menisci and cruciate ligaments in adolescents were as follows: medial meniscus, 92% sensitivity and 87% specificity; lateral meniscus, 93% sensitivity and 95% specificity; anterior cruciate ligament, 100% sensitivity and 100% specificity; and posterior cruciate ligament, 0% sensitivity and 100% specificity. CONCLUSION: Our data suggest that MR imaging of the knee in adolescents is sensitive, specific, and accurate.

Effect of NaCl and NaHCO3 on serum ionised calcium and blood gas status during sprinting.

Sodium bicarbonate is often administered to horses before racing in an attempt to delay fatigue and improve performance. We examined the effect of acid-base status on serum ionised calcium concentration (iCa) during high intensity exercise in 8 Standardbred mares. In a randomised, blinded, cross-over study, mares were administered each of 3 treatments, NaCl (0.7 g/kg bwt), NaHCO3 (1 g/kg bwt) in 3 l water, or 3 l of water only, 4 h before performing a standardised exercise test to fatigue on a treadmill. Mixed venous blood samples were collected as the horses ran for 5 min at 3 m/s, to fatigue at a predetermined speed (approximately 113% VO2max) and for 5 min at 3 m/s. There was no effect of treatment on time to fatigue (P = 0.744). NaHCO3 attenuated (P<0.05) the exercise-induced decrease in venous pH (mean +/- s.e. 6.97, 6.95 and 7.06 +/- 0.02 at end of sprint for water, NaCl and NaHCO3, respectively). Both serum total calcium concentration (tCa) and iCa increased (P<0.05) with running. NaHCO3 decreased iCa (P<0.05) compared to water; iCa of 1.58 and 1.44 +/- 0.04 mmol/l before exercise and 1.69 and 1.49 +/- 0.05 end sprint, for water and NaHCO3 treatments, respectively. These results demonstrate an effect of NaHCO3 on iCa during exercise. Further study is necessary to determine the effect of alterations in iCa on exercise performance.