A psychometric investigation of health-related quality of life measures for paediatric neurodevelopment assessment: Reliability and concurrent validity of the PEDS-QL, CHU-9D, and the EQ-5D-Y.

There is a need for tools that can provide a brief assessment of functioning for children with neurodevelopmental conditions, including health-related quality of life (HR-QoL). This study evaluated the psychometric properties of three commonly used and well known HR-QoL measures in a cohort of children presenting to clinical developmental assessment services. The most common diagnoses received in these assessment services were autism spectrum disorders. Findings showed good internal consistency for the PedsQL and the CHU-9D, but not the EQ-5D-Y. This research also found that the CHU-9D, EQ-5D-Y, and PedsQL correlated with relevant functioning domains assessed by the VABS-III. Overall, the measures showed that children with neurodevelopmental conditions experienced poor HR-QoL. The majority of children (>86%) met cut-off criteria for significant health concerns on the PedsQL. On the EQ-5D-Y and CHU-9D, they showed reduced HR-QoL particularly on domains relating to school and homework, being able to join in activities, looking after self, and doing usual activities. This study supports the use of the CHU-9D and PedsQL in this population to assess and potentially track HR-QoL in a broad neurodevelopment paediatric population.

Using machine learning models to predict falls in hospitalised adults.

BACKGROUND: Identifying patients at high risk of falling is crucial in implementing effective fall prevention programs. While the integration of information systems is becoming more widespread in the healthcare industry, it poses a significant challenge in analysing vast amounts of data to identify factors that could enhance patient safety. OBJECTIVE: To determine fall-associated factors and develop high-performance prediction tools for at-risk patients in acute and sub-acute care services in Australia. METHODS: A retrospective study of 672,400 patients admitted to acute and sub-acute care services within a large metropolitan tertiary health service in Victoria, Australia, between January 1, 2019, and December 31, 2021. Data were obtained from four sources: the Department of Health Victorian Admitted Episodes Dataset, RiskManTM, electronic health records, and the health workforce dataset. Machine learning techniques, including Random Forest and Deep Neural Network models, were used to analyse the data, predict patient falls, and identify the most important risk factors for falls in this population. Model performance was evaluated using accuracy, F1-score, precision, recall, specificity, Matthew's correlation coefficient, and the area under the receiver operating characteristic curve (AUC). RESULTS: The deep neural network and random forest models were highly accurate in predicting hospital patient falls. The deep neural network model achieved an accuracy of 0.988 and a specificity of 0.999, while the RF achieved an accuracy of 0.989 and a specificity of 1.000. The top 20 variables impacting falls were compared across both models, and 12 common factors were identified. These factors can be broadly classified into three categories: patient-related factors, staffing-related factors, and admission-related factors. Although not all factors are modifiable, they must be considered when planning fall prevention interventions. CONCLUSION: The study demonstrated machine learning's potential to predict falls and identify key risk factors. Further validation across diverse populations and settings is essential for broader applicability.

Post-operative volumes following endoscopic surgery for non-functioning pituitary macroadenomas are predictive of further intervention, but not endocrine outcomes.

BACKGROUND: Transsphenoidal surgery (TSS) remains the treatment of choice for non-functioning pituitary macroadenomas (NFPMA). The value of measuring tumour volumes before and after surgery, and its influence on endocrine outcomes and further treatment of the residual or recurrent tumour are unknown. METHODS: Data from patients who underwent endoscopic TSS for a NFPMA (2009-2018) in a UK tertiary centre were analysed for pre- and post-operative endocrine and surgical outcomes. RESULTS: Of 173 patients with NFPMA, 159 (61% male) were treatment naïve. At presentation, 76.2% (77/101) had ≥1 pituitary axis deficit. Older age (p = 0.002) was an independent predictor for multiple hormonal deficiencies. Preoperative tumour volume did not correlate with degree of hypopituitarism. Postoperative tumour volume and extent of tumour resection were not predictive of new onset hypopituitarism. Hormonal recovery was observed in 16 patients (20.8%) with impaired pituitary function, with the greatest recovery in the hypothalamic-pituitary-adrenal axis (21.2%, 7/33). A larger residual tumour volume was predictive of adjuvant radiotherapy (3.40 vs. 1.24 cm3, p = 0.005) and likelihood for repeat surgery (5.40 vs. 1.67cm3, p = 0.004). CONCLUSION: Pre- and post-operative NFPMA volumes fail to predict the number of pituitary hormone deficits, however, greater post-operative residual volumes increase the likelihood of further intervention to control tumour growth.

Resting-State Functional MRI for Determining Language Lateralization in Children with Drug-Resistant Epilepsy.

BACKGROUND AND PURPOSE: Task-based fMRI is a noninvasive method of determining language dominance; however, not all children can complete language tasks due to age, cognitive/intellectual, or language barriers. Task-free approaches such as resting-state fMRI offer an alternative method. This study evaluated resting-state fMRI for predicting language laterality in children with drug-resistant epilepsy. MATERIALS AND METHODS: A retrospective review of 43 children with drug-resistant epilepsy who had undergone resting-state fMRI and task-based fMRI during presurgical evaluation was conducted. Independent component analysis of resting-state fMRI was used to identify language networks by comparing the independent components with a language network template. Concordance rates in language laterality between resting-state fMRI and each of the 4 task-based fMRI language paradigms (auditory description decision, auditory category, verbal fluency, and silent word generation tasks) were calculated. RESULTS: Concordance ranged from 0.64 (95% CI, 0.48-0.65) to 0.73 (95% CI, 0.58-0.87), depending on the language paradigm, with the highest concordance found for the auditory description decision task. Most (78%-83%) patients identified as left-lateralized on task-based fMRI were correctly classified as left-lateralized on resting-state fMRI. No patients classified as right-lateralized or bilateral on task-based fMRI were correctly classified by resting-state fMRI. CONCLUSIONS: While resting-state fMRI correctly classified most patients who had typical (left) language dominance, its ability to correctly classify patients with atypical (right or bilateral) language dominance was poor. Further study is required before resting-state fMRI can be used clinically for language mapping in the context of epilepsy surgery evaluation in children with drug-resistant epilepsy.

Menopause and cognitive complaints: are ovarian hormones linked with subjective cognitive decline?

Subjective cognitive decline (SCD) and the loss of ovarian hormones after menopause have been independently linked to later-life Alzheimer's disease (AD). The objective of this review was to determine whether menopause and the loss of ovarian hormones contribute to cognitive complaints and SCD in women. This would suggest that SCD at the menopausal transition might be an important marker of eventual cognitive decline and AD. We conducted a literature search using PubMed, PsycINFO and Web of Science in July 2020. All English-language studies assessing SCD and cognitive complaints with respect to menopause and ovarian hormones were included. A total of 19 studies were included. Studies found that cognitive complaints increased across the menopause transition and were associated with reductions in attention, verbal and working memory, and medial temporal lobe volume. Women taking estrogen-decreasing treatments also had increased cognitive complaints and reduced working memory and executive function. The current literature provides impetus for further research on whether menopause and the loss of ovarian hormones are associated with cognitive complaints and SCD. Clinicians may take particular note of cognitive complaints after menopause or ovarian hormone loss, as they might presage future cognitive decline.

Hearing loss is associated with gray matter differences in older adults at risk for and with Alzheimer's disease.

Using data from the COMPASS-ND study we investigated associations between hearing loss and hippocampal volume as well as cortical thickness in older adults with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and Alzheimer's dementia (AD). SCD participants with greater pure-tone hearing loss exhibited lower hippocampal volume, but more cortical thickness in the left superior temporal gyrus and right pars opercularis. Greater speech-in-noise reception thresholds were associated with lower cortical thickness bilaterally across much of the cortex in AD. The AD group also showed a trend towards worse speech-in-noise thresholds compared to the SCD group.

X-ray phase imaging with the unified modulated pattern analysis of near-field speckles at a laboratory source.

X-ray phase-contrast techniques are powerful methods for discerning features with similar densities, which are normally indistinguishable with conventional absorption contrast. While these techniques are well-established tools at large-scale synchrotron facilities, efforts have increasingly focused on implementations at laboratory sources for widespread use. X-ray speckle-based imaging is one of the phase-contrast techniques with high potential for translation to conventional x-ray systems. It yields phase-contrast, transmission, and dark-field images with high sensitivity using a relatively simple and cost-effective setup tolerant to divergent and polychromatic beams. Recently, we have introduced the unified modulated pattern analysis (UMPA) [Phys. Rev. Lett.118, 203903 (2017)PRLTAO0031-900710.1103/PhysRevLett.118.203903], which further simplifies the translation of x-ray speckle-based imaging to low-brilliance sources. Here, we present the proof-of-principle implementation of UMPA speckle-based imaging at a microfocus liquid-metal-jet x-ray laboratory source.

Testing the efficacy of kitasamycin for use in the control and treatment of swine dysentery in experimentally infected pigs.

BACKGROUND: Swine dysentery (SD) caused by Brachyspira hyodysenteriae is an important disease in Australia. AIM: The aim of this study is to evaluate the macrolide antibiotic kitasamycin for use in SD control. METHODS: The minimum inhibitory concentrations (MICs) of kitasamycin, tylosin and lincomycin for 32 Australian isolates of B. hyodysenteriae were evaluated. Mutations in the 23S rRNA gene were examined. Isolate '13' with a low kitasamycin MIC was used to challenge weaner pigs. Sixty pigs were housed in 20 pens each containing three pigs: pigs in four pens received 2 kg/tonne of a product containing kitasamycin (3.1% active) prophylactically in their food starting 4 days before B. hyodysenteriae challenge (group 1); pigs in four pens were challenged and received the same dose therapeutically once one pig in a pen showed diarrhoea (group 2); four pens were challenged and received 4 kg/tonne of the product therapeutically (group 3); four pens were challenged but not medicated (group 4); two pens were unmedicated and unchallenged (group 5) and two pens received 2 kg/tonne and were unchallenged (group 6). Pigs were monitored for B. hyodysenteriae excretion and disease. RESULTS: Macrolide resistance was widespread, and mutations in the 23S rRNA gene were identified in 23 isolates. Four isolates with kitasamycin MICs < 5 µg/mL were considered susceptible. Following experimental challenge, 10 of 12 unmedicated pigs developed SD. No pigs receiving kitasamycin prophylactical or therapeutically developed SD. Medicated pigs shed low numbers of B. hyodysenteriae in their faeces. CONCLUSIONS: Kitasamycin can help control SD in pigs infected with susceptible isolates of B. hyodysenteriae.

Maternal, infant and childhood risks associated with advanced paternal age: The need for comprehensive counseling for men.

The increasing maternal age at first birth is well recognized, but much less discussed are the fact that the prevalence of advanced paternal age (APA) is also increasing and the societal implications of this trend. Over the past 40 years in the United States, the proportion of infants born to fathers of APA, which has been variably defined as above 35 or above 45, increased from ˜4% to 10% (Khandwala et al., 2017, 2018) While there has been extensive research regarding infertility and comorbidities in the aging mother, relatively few studies have explored similar reproductive factors in aging men. However, evidence does suggest a decrease in fertility and an increase in pregnancy complications such as gestational diabetes, intrauterine growth restriction and preterm birth. Additionally, the offspring of fathers of APA have increased risks of chromosomal and non-chromosomal birth defects and an increased incidence of childhood autism and cancers. This review explores the data, with the intent that key counseling points, including the suggestion of sperm banking, can be highlighted when advising the midlife and older man who is considering paternity.

Laryngeal amyloidosis: diagnosis, pathophysiology and management.

BACKGROUND: Laryngeal amyloidosis represents approximately 1 per cent of all benign laryngeal lesions, and can cause variable symptoms depending on anatomical location and size. Treatment ranges from observation through to endoscopic microsurgery, laser excision and laryngectomy. OBJECTIVES: To highlight the diversity of presentations, increase awareness of paediatric amyloidosis and update the reader on current management. CASE SERIES: Five cases are illustrated. Four adult patients were female, and the one child, the second youngest in the literature, was male. Amyloid deposits were identified in all laryngeal areas, including the supraglottis, glottis and subglottis. Treatment consisted of balloon dilatation, endoscopic excision, laser cruciate incision, and resection with carbon dioxide laser, a microdebrider and coblation wands. CONCLUSION: Laryngeal amyloidosis remains a rare and clinically challenging condition. Diagnosis should be considered for unusual appearing submucosal laryngeal lesions. Treatment of this disease needs to be evaluated on a case-by-case basis and managed within an appropriate multidisciplinary team.

A novel method for quantitative measurements of gene expression in single living cells.

Gene expression is at the heart of virtually any biological process, and its deregulation is at the source of numerous pathological conditions. While impressive progress has been made in genome-wide measurements of mRNA and protein expression levels, it is still challenging to obtain highly quantitative measurements in single living cells. Here we describe a novel approach based on internal tagging of endogenous proteins with a reporter allowing luminescence and fluorescence time-lapse microscopy. Using luminescence microscopy, fluctuations of protein expression levels can be monitored in single living cells with high sensitivity and temporal resolution over extended time periods. The integrated protein decay reporter allows measuring protein degradation rates in the absence of protein synthesis inhibitors, and in combination with absolute protein levels allows determining absolute amounts of proteins synthesized over the cell cycle. Finally, the internal tag can be excised by inducible expression of Cre recombinase, which enables to estimate endogenous mRNA half-lives. Our method thus opens new avenues in quantitative analysis of gene expression in single living cells.

Bragg coherent diffraction imaging and metrics for radiation damage in protein micro-crystallography.

The proliferation of extremely intense synchrotron sources has enabled ever higher-resolution structures to be obtained using data collected from smaller and often more imperfect biological crystals (Helliwell, 1984). Synchrotron beamlines now exist that are capable of measuring data from single crystals that are just a few micrometres in size. This provides renewed motivation to study and understand the radiation damage behaviour of small protein crystals. Reciprocal-space mapping and Bragg coherent diffractive imaging experiments have been performed on cryo-cooled microcrystals of hen egg-white lysozyme as they undergo radiation damage. Several well established metrics, such as intensity-loss and lattice expansion, are applied to the diffraction data and the results are compared with several new metrics that can be extracted from the coherent imaging experiments. Individually some of these metrics are inconclusive. However, combining metrics, the results suggest that radiation damage behaviour in protein micro-crystals differs from that of larger protein crystals and may allow them to continue to diffract for longer. A possible mechanism to account for these observations is proposed.

Hyperpolarizability and Operational Magic Wavelength in an Optical Lattice Clock.

Optical clocks benefit from tight atomic confinement enabling extended interrogation times as well as Doppler- and recoil-free operation. However, these benefits come at the cost of frequency shifts that, if not properly controlled, may degrade clock accuracy. Numerous theoretical studies have predicted optical lattice clock frequency shifts that scale nonlinearly with trap depth. To experimentally observe and constrain these shifts in an ^{171}Yb optical lattice clock, we construct a lattice enhancement cavity that exaggerates the light shifts. We observe an atomic temperature that is proportional to the optical trap depth, fundamentally altering the scaling of trap-induced light shifts and simplifying their parametrization. We identify an "operational" magic wavelength where frequency shifts are insensitive to changes in trap depth. These measurements and scaling analysis constitute an essential systematic characterization for clock operation at the 10^{-18} level and beyond.

Increased dietary protein in the second trimester of gestation increases live weight gain and carcass composition in weaner calves to 6 months of age.

Genetically similar nulliparous Polled Hereford heifers from a closed pedigree herd were used to evaluate the effects of dietary protein during the first and second trimester of gestation upon foetal, placental and postnatal growth. Heifers were randomly allocated into two groups at 35 days after artificial insemination (35 days post conception (dpc)) to a single bull and fed high (15.7% CP) or low (5.9% CP) protein in the first trimester (T1). At 90 dpc, half of each nutritional treatment group changed to a high- or low-protein diet for the second trimester until 180 dpc (T2). High protein intake in the second trimester increased birth weight in females (P=0.05), but there was no effect of treatment upon birth weight when taken over both sexes. Biparietal diameter was significantly increased by high protein in the second trimester with the effect being greater in the female (P=0.02), but also significant overall (P=0.05). Placental weight was positively correlated with birth weight, fibroblast volume and relative blood vessel volume (P<0.05). Placental fibroblast density was increased and trophoblast volume decreased in the high-protein first trimester treatment group (P<0.05). There was a trend for placental weight to be increased by high protein in the second trimester (P=0.06). Calves from heifers fed the high-protein treatment in the second trimester weighed significantly more on all occasions preweaning (at 1 month (P=0.0004), 2 months (P=0.006), 3 months (P=0.002), 4 months (P=0.01), 5 months (P=0.03), 6 months (P=0.001)), and grew at a faster rate over the 6-month period. By 6 months of age, the calves from heifers fed high nutrition in the second trimester weighed 33 kg heavier than those fed the low diet in the second trimester. These results suggest that dietary protein in early pregnancy alters the development of the bovine placenta and calf growth to weaning.

Melioidosis in a patient with chronic rhinosinusitis.

BACKGROUND: Melioidosis is a serious infection caused by soil-dwelling Gram-negative bacillus Burkholderia pseudomallei. It is most commonly reported in Northern Australia, Southeast and Southern Asia, China, and Taiwan. METHODS: A case report and short review of the literature are presented. Presentation, diagnosis including genomic sequencing, and acute and long-term management are discussed. RESULTS: A 58-year-old female presented with chronic rhinosinusitis secondary to melioidosis. This is the third reported incidence of sinusitis secondary to melioidosis, which occurred in an otherwise well female with no risk factors and no apparent cause of exposure. Treatment involved an acute phase in which meropenem was administered parenterally for two weeks, followed by a prolonged oral course of trimethoprim-sulfamethoxazole for three months, as per recommended guidelines. CONCLUSION: In patients presenting with refractory chronic rhinosinusitis, ENT surgeons should consider the presence of unusual causative pathogens such as B pseudomallei, particularly in those with recent travel history to Northern Queensland and/or Southeast Asia.

How I do it - endoscopic endonasal approach for pituitary tumour.

BACKGROUND: Endoscopic endonasal surgery to access the anterior skull base has evolved in many centres worldwide and provides a minimally invasive alternative, with better patient experience, to open techniques. METHOD: We present a basic approach to a midline lesion that is the fundamental starting point for wider access to the skull base. CONCLUSION: The nuances of this technique illustrated here have been developed in many centres to provide a safe procedure that has a low incidence of complications and excellent potential.

A non-invasive method to produce pressure ulcers of varying severity in a spinal cord-injured rat model.

STUDY DESIGN: Experimental study. OBJECTIVES: The objective of this study was to establish a non-invasive model to produce pressure ulcers of varying severity in animals with spinal cord injury (SCI). SETTING: The study was conducted at the Johns Hopkins Hospital in Baltimore, Maryland, USA. METHODS: A mid-thoracic (T7-T9) left hemisection was performed on Sprague-Dawley rats. At 7 days post SCI, rats received varying degrees of pressure on the left posterior thigh region. Laser Doppler Flowmetry was used to record blood flow. Animals were killed 12 days after SCI. A cardiac puncture was performed for blood chemistry, and full-thickness tissue was harvested for histology. RESULTS: Doppler blood flow after SCI prior to pressure application was 237.808±16.175 PFUs at day 7. Following pressure application, there was a statistically significant decrease in blood flow in all pressure-applied groups in comparison with controls with a mean perfusion of 118.361±18.223 (P<0.001). White blood cell counts and creatine kinase for each group were statistically significant from the control group (P=0.0107 and P=0.0028, respectively). CONCLUSIONS: We have created a novel animal model of pressure ulcer formation in the setting of a SCI. Histological analysis revealed different stages of injury corresponding to the amount of pressure the animals were exposed to with decreased blood flow immediately after the insult along with a subsequent marked increase in blood flow the next day, conducive to an ischemia-reperfusion injury (IRI) and a possible inflammatory response following tissue injury. Following ischemia and hypoxia secondary to microcirculation impairment, free radicals generate lipid peroxidation, leading to ischemic tissue damage. Future studies should be aimed at measuring free radicals during this period of increased blood flow, following tissue ischemia.

Prevalence, codetection and seasonal distribution of upper airway viruses and bacteria in children with acute respiratory illnesses with cough as a symptom.

Most studies exploring the role of upper airway viruses and bacteria in paediatric acute respiratory infections (ARI) focus on specific clinical diagnoses and/or do not account for virus-bacteria interactions. We aimed to describe the frequency and predictors of virus and bacteria codetection in children with ARI and cough, irrespective of clinical diagnosis. Bilateral nasal swabs, demographic, clinical and risk factor data were collected at enrollment in children aged <15 years presenting to an emergency department with an ARI and where cough was a symptom. Swabs were tested by polymerase chain reaction for 17 respiratory viruses and seven respiratory bacteria. Logistic regression was used to investigate associations between child characteristics and codetection of the organisms of interest. Between December 2011 and August 2014, swabs were collected from 817 (93.3%) of 876 enrolled children, median age 27.7 months (interquartile range 13.9-60.3 months). Overall, 740 (90.6%) of 817 specimens were positive for any organism. Both viruses and bacteria were detected in 423 specimens (51.8%). Factors associated with codetection were age (adjusted odds ratio (aOR) for age <12 months = 4.9, 95% confidence interval (CI) 3.0, 7.9; age 12 to <24 months = 6.0, 95% CI 3.7, 9.8; age 24 to <60 months = 2.4, 95% CI 1.5, 3.9), male gender (aOR 1.46; 95% CI 1.1, 2.0), child care attendance (aOR 2.0; 95% CI 1.4, 2.8) and winter enrollment (aOR 2.0; 95% CI 1.3, 3.0). Haemophilus influenzae dominated the virus-bacteria pairs. Virus-H. influenzae interactions in ARI should be investigated further, especially as the contribution of nontypeable H. influenzae to acute and chronic respiratory diseases is being increasingly recognized.

Seeking the sun in deep, dark places: mesopelagic sightings of ocean sunfishes (Molidae).

Evidence is presented from publicly available remotely operated vehicle (ROV) footage that suggests deep-water ranging in ocean sunfishes (family Molidae) is more common than typically thought, including a new maximum depth recorded for the southern sunfish Mola ramsayi.