Integrative Salt Selection and Formulation Optimization: Perspectives of Disproportionation and Microenvironmental pH Modulation.

We report a novel utilization of a pH modifier as a disproportionation retardant in a tablet formulation. The drug molecule of interest has significant bioavailability challenges that require solubility enhancement. In addition to limited salt/cocrystal options, disproportionation of the potential salt(s) was identified as a substantial risk. Using a combination of Raman spectroscopy with chemometrics and quantitative X-ray diffraction in specially designed stress testing, we investigated the disproportionation phenomena. The learnings and insight drawn from crystallography drove the selection of the maleate form as the target API. Inspired by the fumarate form's unique stability and solubility characteristics, we used fumaric acid as the microenvironmental pH modulator. Proof-of-concept experiments with high-risk (HCl) and moderate-risk (maleate) scenarios confirmed the synergistic advantage of fumaric acid, which interacts with the freebase released by disproportionation to form a more soluble species. The resultant hemifumarate helps maintain the solubility at an elevated level. This work demonstrates an innovative technique to mediate the solubility drop during the "parachute" phase of drug absorption using compendial excipients, and this approach can potentially serve as an effective risk-mitigating strategy for salt disproportionation.

Predictive performance of the common red flags in emergency department headache patients: a HEAD and HEAD-Colombia study.

OBJECTIVES: Only a small proportion of patients presenting to an ED with headache have a serious cause. The SNNOOP10 criteria, which incorporates red and orange flags for serious causes, has been proposed but not well studied. This project aims to compare the proportion of patients with 10 commonly accepted red flag criteria (singly and in combination) between patients with and without a diagnosis of serious secondary headache in a large, multinational cohort of ED patients presenting with headache. METHODS: Secondary analysis of data obtained in the HEAD and HEAD-Colombia studies. The outcome of interest was serious secondary headache. The predictive performance of 10 red flag criteria from the SNNOOP10 criteria list was estimated individually and in combination. RESULTS: 5293 patients were included, of whom 6.1% (95% CI 5.5% to 6.8%) had a defined serious cause identified. New neurological deficit, history of neoplasm, older age (>50 years) and recent head trauma (2-7 days prior) were independent predictors of a serious secondary headache diagnosis. After adjusting for other predictors, sudden onset, onset during exertion, pregnancy and immune suppression were not associated with a serious headache diagnosis. The combined sensitivity of the red flag criteria overall was 96.5% (95% CI 93.2% to 98.3%) but specificity was low, 5.1% (95% CI 4.3% to 6.0%). Positive predictive value was 9.3% (95% CI 8.2% to 10.5%) with negative predictive value of 93.5% (95% CI 87.6% to 96.8%). CONCLUSION: The sensitivity and specificity of the red flag criteria in this study were lower than previously reported. Regarding clinical practice, this suggests that red flag criteria may be useful to identify patients at higher risk of a serious secondary headache cause, but their low specificity could result in increased rates of CT scanning. TRIAL REGISTRATION NUMBER: ANZCTR376695.

Metabolic flux analysis of the non-transitory starch tradeoff for lipid production in mature tobacco leaves.

The metabolic plasticity of tobacco leaves has been demonstrated via the generation of transgenic plants that can accumulate over 30% dry weight as triacylglycerols. In investigating the changes in carbon partitioning in these high lipid-producing (HLP) leaves, foliar lipids accumulated stepwise over development. Interestingly, non-transient starch was observed to accumulate with plant age in WT but not HLP leaves, with a drop in foliar starch concurrent with an increase in lipid content. The metabolic carbon tradeoff between starch and lipid was studied using 13CO2-labeling experiments and isotopically nonstationary metabolic flux analysis, not previously applied to the mature leaves of a crop. Fatty acid synthesis was investigated through assessment of acyl-acyl carrier proteins using a recently derived quantification method that was extended to accommodate isotopic labeling. Analysis of labeling patterns and flux modeling indicated the continued production of unlabeled starch, sucrose cycling, and a significant contribution of NADP-malic enzyme to plastidic pyruvate production for the production of lipids in HLP leaves, with the latter verified by enzyme activity assays. The results suggest an inherent capacity for a developmentally regulated carbon sink in tobacco leaves and may in part explain the uniquely successful leaf lipid engineering efforts in this crop.

Temporal changes in metabolism late in seed development affect biomass composition.

The negative association between protein and oil production in soybean (Glycine max) seed is well-documented. However, this inverse relationship is based primarily on the composition of mature seed, which reflects the cumulative result of events over the course of soybean seed development and therefore does not convey information specific to metabolic fluctuations during developmental growth regimes. In this study, we assessed maternal nutrient supply via measurement of seed coat exudates and metabolite levels within the cotyledon throughout development to identify trends in the accumulation of central carbon and nitrogen metabolic intermediates. Active metabolic activity during late seed development was probed through transient labeling with 13C substrates. The results indicated: (1) a drop in lipid contents during seed maturation with a concomitant increase in carbohydrates, (2) a transition from seed filling to maturation phases characterized by quantitatively balanced changes in carbon use and CO2 release, (3) changes in measured carbon and nitrogen resources supplied maternally throughout development, (4) 13C metabolite production through gluconeogenic steps for sustained carbohydrate accumulation as the maternal nutrient supply diminishes, and (5) oligosaccharide biosynthesis within the seed coat during the maturation phase. These results highlight temporal engineering targets for altering final biomass composition to increase the value of soybeans and a path to breaking the inverse correlation between seed protein and oil content.

An efficient LC-MS method for isomer separation and detection of sugars, phosphorylated sugars, and organic acids.

Assessing central carbon metabolism in plants can be challenging due to the dynamic range in pool sizes, with low levels of important phosphorylated sugars relative to more abundant sugars and organic acids. Here, we report a sensitive liquid chromatography-mass spectrometry method for analysing central metabolites on a hybrid column, where both anion-exchange and hydrophilic interaction chromatography (HILIC) ligands are embedded in the stationary phase. The liquid chromatography method was developed for enhanced selectivity of 27 central metabolites in a single run with sensitivity at femtomole levels observed for most phosphorylated sugars. The method resolved phosphorylated hexose, pentose, and triose isomers that are otherwise challenging. Compared with a standard HILIC approach, these metabolites had improved peak areas using our approach due to ion enhancement or low ion suppression in the biological sample matrix. The approach was applied to investigate metabolism in high lipid-producing tobacco leaves that exhibited increased levels of acetyl-CoA, a precursor for oil biosynthesis. The application of the method to isotopologue detection and quantification was considered through evaluating 13C-labeled seeds from Camelina sativa. The method provides a means to analyse intermediates more comprehensively in central metabolism of plant tissues.

Migraine in the Emergency Department: A Prospective Multinational Study of Patient Characteristics, Management, and Outcomes.

BACKGROUND AND AIM: Migraine headache is commonly diagnosed in emergency departments (ED). There is relatively little real-world information about the epidemiology, investigation, management, adherence to therapeutic guidelines and disposition of patients treated in ED with a final diagnosis of migraine. The primary aim of the current study is to get a snapshot of assessment and management patterns of acute migraine presentations to the different settings of EDs with a view to raise awareness. METHODS: This is a planned sub-study of a prospective study conducted in 67 health services in 10 countries including Australia, New Zealand, Southeast Asia, Europe, and the UK investigating the epidemiology and outcome of adult patients presenting to ED with nontraumatic headache. Outcomes of interest for this study are demographics, clinical features (including severity), patterns of investigation, treatment, disposition, and outcome of patients diagnosed as having migraine as their final ED diagnosis. RESULTS: The cohort comprises 1,101 patients with a mean age of 39 years (SD ± 13.5; 73.7% [811]) were female. Most patients had had migraine diagnosed previously (77.7%). Neuroimaging was performed in 25.9% with a very low diagnostic yield or significant findings (0.07%). Treatment of mild migraine was in accordance with current guidelines, but few patients with moderate or severe symptoms received recommended treatment. Paracetamol (46.3%) and nonsteroidal anti-inflammatory drugs (42.7%) were the most commonly prescribed agents. Metoclopramide (22.8%), ondansetron (19.2%), chlorpromazine (12.8%), and prochlorperazine (12.8%) were also used. CONCLUSIONS: This study suggests that therapeutic practices are not congruent with current guidelines, especially for patients with severe symptoms. Efforts to improve and sustain compliance with existing management best practices are required.

Valorization of spent brewery yeast biosorbent with sonication-assisted adsorption for dye removal in wastewater treatment.

The effluent of textile industries containing synthetic dyes contributed to substantial pollution to water bodies. The biosorption process of Congo Red dye was successfully performed by integrating ultrasonication in the adsorption step with spent brewery yeast as a novel and renewable biosorbent. The adsorption process was hindered when ultrasonication was employed together with the biosorbent, indicating that desorption process had occurred. The adsorption process showed that 4 g/L of biosorbent was the optimum dosage for adsorption of 50 mg/L of Congo Red dye, and that the adsorption equilibrium fitted to the Langmuir model, with kinetics best fitted with pseudo-second order model. The maximum capacity of the adsorption was 52.6 mg/g, showing the potential of spent brewery yeast to aid in removing wastewater pollutants. Maximal Congo Red dye recovery (100%) was achieved in the sonication-assisted desorption studies using 0.01M NaOH as the eluting agent. The ultrasonication effects contributed to the efficient recovery of dye and good conversion of spent brewery yeast to biosorbent can be beneficial for treating pollution from textile wastewater.

Thunderclap headache syndrome presenting to the emergency department: an international multicentre observational cohort study.

BACKGROUND: Most headache presentations to emergency departments (ED) have benign causes; however, approximately 10% will have serious pathology. International guidelines recommend that patients describing the onset of headache as 'thunderclap' undergo neuroimaging and further investigation. The association of this feature with serious headache cause is unclear. The objective of this study was to determine if patients presenting with thunderclap headache are significantly more likely to have serious underlying pathology than patients with more gradual onset and to determine compliance with guidelines for investigation. METHODS: This was a planned secondary analysis of an international, multicentre, observational study of adult ED patients presenting with a main complaint of headache. Data regarding demographics, investigation strategies and final ED diagnoses were collected. Thunderclap headache was defined as severe headache of immediate or almost immediate onset and peak intensity. Proportion of patients with serious pathology in thunderclap and non-thunderclap groups were compared by χ² test. RESULTS: 644 of 4536 patients presented with thunderclap headache (14.2%). CT brain imaging and lumbar puncture were performed in 62.7% and 10.6% of cases, respectively. Among patients with thunderclap headache, serious pathology was identified in 10.9% (95%CI 8.7% to 13.5%) of cases-significantly higher than the proportion found in patients with a different headache onset (6.6% (95% CI 5.9% to 7.4%), p<0.001.). The incidence of subarachnoid haemorrhage (SAH) was 3.6% (95% CI 2.4% to 5.3%) in those with thunderclap headache vs 0.3% (95% CI 0.2% to 0.5%) in those without (p<0.001). All cases of SAH were diagnosed on CT imaging. Non-serious intracranial pathology was diagnosed in 87.7% of patients with thunderclap headache. CONCLUSIONS: Thunderclap headache presenting to the ED appears be associated with higher risk for serious intracranial pathology, including SAH, although most patients with this type of headache had a benign cause. Neuroimaging rates did not align with international guidelines, suggesting potential need for further work on standardisation.

When is it too late? Ovarian preservation and duration of symptoms in ovarian torsion.

This 10-year retrospective study between 2008 and 2018, aims to investigate the duration of symptoms of ovarian torsion and the subsequent rate of ovarian preservation. Eighty-six women with surgically confirmed ovarian torsion were included. The median duration from the onset of pain symptoms to presentation (26.0 vs 6.0 h, p < .001) and from presentation to surgery (11.0 vs 5.5 h, p = .010) were significantly longer in women who required an oophorectomy compared to women who had conservative surgery. There was no significant difference in symptoms, signs or investigations except ultrasound finding of an enlarged ovary (94.9% vs 76.9%, p = .026). Awareness of the condition among the community and healthcare is crucial and routine investigations should not delay management as positive Doppler flow on ultrasound does not exclude an ovarian torsion.Impact StatementWhat is already known on this subject? Ovarian torsion is a gynaecological emergency and may lead to ovarian necrosis, infection and peritonitis. Early recognition is essential in preserving the ovary, particularly in patients with future fertility aspirations. Currently there is no consensus regarding the time period of ovarian viability after the onset of symptoms.What do the results of this study add? We have demonstrated a significant difference in the duration from the onset of symptoms to surgery. Furthermore, the duration from the onset of symptoms to presentation (26.0 vs 6.0 h, p<.001) and from presentation to surgery (11.0 vs 5.5 h, p=.010) were significantly longer in women who required an oophorectomy compared to women who had conservative surgery. There was no significant difference in symptoms, signs or investigations except ultrasound finding of an enlarged ovary.What are the implications of these findings for clinical practice and/or further research? Women with known ovarian cysts in particular should be educated of the risk of ovarian torsion. Routine investigations should not delay management as it does not exclude an ovarian torsion. Although our study suggests that early presentation and management would reduce the risk of oophorectomy, prospective studies are required to confirm the findings.

A Quiet Compassion.

Through a difficult encounter with a new patient, the author became immersed in the messiness of patient care and learned that goals need to be defined and hard fought. The lesson learned serves as a reminder that compassion for our patients is necessary to help understand their fears and anxieties.

The Headache in Emergency Departments study: Opioid prescribing in patients presenting with headache. A multicenter, cross-sectional, observational study.

OBJECTIVE: To describe the patterns of opioid use in patients presenting to the emergency department (ED) with nontraumatic headache by severity and geography. BACKGROUND: International guidelines recognize opioids are ineffective in treating primary headache disorders. Globally, many countries are experiencing an opioid crisis. The ED can be a point of initial exposure leading to tolerance for patients. More geographically diverse data are required to inform practice. METHODS: This was a planned, multicenter, cross-sectional, observational substudy of the international Headache in Emergency Departments (HEAD) study. Participants were prospectively identified throughout March 2019 from 67 hospitals in Europe, Asia, Australia, and New Zealand. Adult patients with nontraumatic headache were included as identified by the local site investigator. RESULTS: Overall, 4536 patients were enrolled in the HEAD study. Opioids were administered in 1072/4536 (23.6%) patients in the ED, and 386/3792 (10.2%) of discharged patients. High opioid use occurred prehospital in Australia (190/1777, 10.7%) and New Zealand (55/593, 9.3%). Opioid use in the ED was highest in these countries (Australia: 586/1777, 33.0%; New Zealand: 221/593, 37.3%). Opioid prescription on discharge was highest in Singapore (125/442, 28.3%) and Hong Kong (12/49, 24.5%). Independent predictors of ED opioid administration included the following: severe headache (OR 4.2, 95% CI 3.1-5.5), pre-ED opioid use (OR 1.42, 95% CI 1.11-1.82), and long-term opioid use (OR 1.80, 95% CI 1.26-2.58). ED opioid administration independently predicted opioid prescription at discharge (OR 8.4, 95% CI 6.3-11.0). CONCLUSION: Opioid prescription for nontraumatic headache in the ED and on discharge varies internationally. Severe headache, prehospital opioid use, and long-term opioid use predicted ED opioid administration. ED opioid administration was a strong predictor of opioid prescription at discharge. These findings support education around policy and guidelines to ensure adherence to evidence-based interventions for headache.

Epidemiology, investigation, management, and outcome of headache in emergency departments (HEAD study)-A multinational observational study.

OBJECTIVE: To describe the epidemiology of nontraumatic headache in adults presenting to emergency departments (EDs). BACKGROUND: Headache is a common reason for presentation to EDs. Little is known about the epidemiology, investigation, and treatment of nontraumatic headache in patients attending EDs internationally. METHODS: An international, multicenter, observational, cross-sectional study was conducted over one calendar month in 2019. Participants were adults (≥18 years) with nontraumatic headache as the main presenting complaint. Exclusion criteria were recent head trauma, missing records, interhospital transfers, re-presentation with same headache as a recent visit, and headache as an associated symptom. Data collected included demographics, clinical assessment, investigation, treatment, and outcome. RESULTS: We enrolled 4536 patients (67 hospitals, 10 countries). "Thunderclap" onset was noted in 14.2% of cases (644/4536). Headache was rated as severe in 27.2% (1235/4536). New neurological examination findings were uncommon (3.2%; 147/4536). Head computed tomography (CT) was performed in 36.6% of patients (1661/4536), of which 9.9% showed clinically important pathology (165/1661). There was substantial variation in CT scan utilization between countries (15.9%-75.0%). More than 30 different diagnoses were made. Presumed nonmigraine benign headache accounted for 45.4% of cases (2058/4536) with another 24.3% classified as migraine (1101/4536). A small subgroup of patients have a serious secondary cause for their headache (7.1%; 323/4536) with subarachnoid hemorrhage (SAH), stroke, neoplasm, non-SAH intracranial hemorrhage/hematoma, and meningitis accounting for about 1% each. Most patients were treated with simple analgesics (paracetamol, aspirin, or nonsteroidal anti-inflammatory agents). Most patients were discharged home (83.8%; 3792/4526). In-hospital mortality was 0.3% (11/4526). CONCLUSION: Diagnosis and management of headache in the ED is challenging. A small group of patients have a serious secondary cause for their symptoms. There is wide variation in the use of neuroimaging and treatments. Further work is needed to understand the variation in practice and to better inform international guidelines regarding emergent neuroimaging and treatment.

Adult plant resistance in maize to northern leaf spot is a feature of partial loss-of-function alleles of Hm1.

Adult plant resistance (APR) is an enigmatic phenomenon in which resistance genes are ineffective in protecting seedlings from disease but confer robust resistance at maturity. Maize has multiple cases in which genes confer APR to northern leaf spot, a lethal disease caused by Cochliobolus carbonum race 1 (CCR1). The first identified case of APR in maize is encoded by a hypomorphic allele, Hm1A, at the hm1 locus. In contrast, wild-type alleles of hm1 provide complete protection at all developmental stages and in every part of the maize plant. Hm1 encodes an NADPH-dependent reductase, which inactivates HC-toxin, a key virulence effector of CCR1. Cloning and characterization of Hm1A ruled out differential transcription or translation for its APR phenotype and identified an amino acid substitution that reduced HC-toxin reductase (HCTR) activity. The possibility of a causal relationship between the weak nature of Hm1A and its APR phenotype was confirmed by the generation of two new APR alleles of Hm1 by mutagenesis. The HCTRs encoded by these new APR alleles had undergone relatively conservative missense changes that partially reduced their enzymatic activity similar to HM1A. No difference in accumulation of HCTR was observed between adult and juvenile plants, suggesting that the susceptibility of seedlings derives from a greater need for HCTR activity, not reduced accumulation of the gene product. Conditions and treatments that altered the photosynthetic output of the host had a dramatic effect on resistance imparted by the APR alleles, demonstrating a link between the energetic or metabolic status of the host and disease resistance affected by HC-toxin catabolism by the APR alleles of HCTR.

Phasic inhibition as a mechanism for generation of rapid respiratory rhythms.

Central neural networks operate continuously throughout life to control respiration, yet mechanisms regulating ventilatory frequency are poorly understood. Inspiration is generated by the pre-Bötzinger complex of the ventrolateral medulla, where it is thought that excitation increases inspiratory frequency and inhibition causes apnea. To test this model, we used an in vitro optogenetic approach to stimulate select populations of hindbrain neurons and characterize how they modulate frequency. Unexpectedly, we found that inhibition was required for increases in frequency caused by stimulation of Phox2b-lineage, putative CO2-chemosensitive neurons. As a mechanistic explanation for inhibition-dependent increases in frequency, we found that phasic stimulation of inhibitory neurons can increase inspiratory frequency via postinhibitory rebound. We present evidence that Phox2b-mediated increases in frequency are caused by rebound excitation following an inhibitory synaptic volley relayed by expiration. Thus, although it is widely thought that inhibition between inspiration and expiration simply prevents activity in the antagonistic phase, we instead propose a model whereby inhibitory coupling via postinhibitory rebound excitation actually generates fast modes of inspiration.

The relationship between time to analgesic administration and emergency department length of stay: A retrospective review.

AIM: To determine the association between time to first analgesic medication and emergency department length of stay (ED LOS). DESIGN: Retrospective cohort study. METHOD: We conducted this study in a large, inner-city emergency department and included adult patients who presented with pain as a symptom and received analgesic medication(s). Study participants were identified from a random selection of 2,000 adult patients who presented between August-October 2018. The relationship between ED LOS and time to first analgesic medication was described using bivariate and multivariate linear regression. RESULTS: Of the 2,000 randomly selected patients presenting between August and October 2018, 727 (36.35%) had pain as a symptom on arrival, 423 (21.15%) had analgesic medication administered. The median time to first analgesic medication was in 62 (interquartile range: 36-105) minutes and median ED LOS was 218 (interquartile range: 160-317.5) minutes. After adjusting for the effects of sex, urgency of the presentation, emergency department location first seen by clinician, departure destination and workload metrics (average daily time to be seen and daily access block). Time to first analgesic medication was independently associated with ED LOS, contributing to 6.96% of the variance in the multivariate model. CONCLUSION: Providing analgesic medication faster to patients presenting in pain, in addition to previously demonstrated positive patient outcomes, may decrease their ED LOS. IMPACT: Reducing ED LOS through faster pain care, benefits the patient through faster pain relief and can benefit the department by reducing the total amount of care delivered in the emergency department. Reducing total care delivery frees up resources to improve the care to all emergency department patients.

Gaze coordination with strides during walking in the cat.

KEY POINTS: Vision plays a crucial role in guiding locomotion in complex environments, but the coordination between gaze and stride is not well understood. The coordination of gaze shifts, fixations, constant gaze and slow gaze with strides in cats walking on different surfaces were examined. It was found that gaze behaviours are coordinated with strides even when walking on a flat surface in the complete darkness, occurring in a sequential order during different phases of the stride. During walking on complex surfaces, gaze behaviours are typically more tightly coordinated with strides, particularly at faster speeds, only slightly shifting in phase. These findings indicate that the coordination of gaze behaviours with strides is not vision-driven, but is a part of the whole body locomotion synergy; the visual environment and locomotor task modulate it. The results may be relevant to developing diagnostic tools and rehabilitation approaches for patients with locomotor deficits. ABSTRACT: Vision plays a crucial role in guiding locomotion in complex environments. However, the coordination between the gaze and stride is not well understood. We investigated this coordination in cats walking on a flat surface in darkness or light, along a horizontal ladder and on a pathway with small stones. We recorded vertical and horizontal eye movements and 3-D head movement, and calculated where gaze intersected the walkway. The coordination of gaze shifts away from the animal, gaze shifts toward, fixations, constant gaze, and slow gaze with strides was investigated. We found that even during walking on the flat surface in the darkness, all gaze behaviours were coordinated with strides. Gaze shifts and slow gaze toward started in the beginning of each forelimb's swing and ended in its second half. Fixations peaked throughout the beginning and middle of swing. Gaze shifts away began throughout the second half of swing of each forelimb and ended when both forelimbs were in stance. Constant gaze and slow gaze away occurred in the beginning of stance. However, not every behaviour occurred during every stride. Light had a small effect. The ladder and stones typically increased the coordination and caused gaze behaviours to occur 3% earlier in the cycle. At faster speeds, the coordination was often tighter and some gaze behaviours occurred 2-16% later in the cycle. The findings indicate that the coordination of gaze with strides is not vision-driven, but is a part of the whole body locomotion synergy; the visual environment and locomotor task modulate it.

Consideration of gender differences in infertility evaluation.

PURPOSE OF REVIEW: We aim to provide a review of the literature to summarize the potential causes that lead to a disparity in infertility evaluation and the implications of male factor infertility. RECENT FINDINGS: Owing to current social constructs, women are more likely to seek medical attention and establish reproductive health evaluation at an earlier age. The male factor evaluation in infertility usually gets delayed and can contribute to a couple's inability to conceive. Furthermore, the cost of assisted reproductive technology is not inconsequential and identifying reversible causes of male infertility could lead to substantial cost-savings to the couple. Additionally, male infertility has been identified as a potential early surrogate for adverse health outcomes and an early identification could serve to counsel these patients on lifestyle modification. SUMMARY: Infertility is defined as the inability to conceive after 12 months of unprotected intercourse with 15% of couples reporting difficulties in conception. Traditionally, female factor evaluation has been the driver for the infertility workup. It is estimated that male factor is likely to play a role in 50% of infertile couples with sole contribution in 20% of cases. It is therefore crucial to ensure appropriate investigations of both partners to rule out potentially reversible causes of infertility to improve their chances of natural fecundity.

Artificial Intelligence in Reproductive Urology.

PURPOSE OF REVIEW: The promise of artificial intelligence (AI) in medicine has been widely theorized over the past couple of decades. It has only been with technological advances over the past few years that physicians and computer scientists have started discovering its true clinical potential. Reproductive urology is a sub-discipline that AI could be of great contribution, as current predictive models and subjectivity within the field have several limitations. We review the literature to summarize recent AI applications in reproductive urology. RECENT FINDINGS: Early AI applications in reproductive urology focused on predicting semen parameters based on questionnaires that identify potential environmental factors and/or lifestyle habits impacting male fertility. AI has shown success in predicting the patient subpopulation most likely to need a genetic workup for azoospermia. With recent advances in image processing, automated sperm detection is a reality. Semen analyses, once a laboratory-only diagnostic test, have moved into health consumer homes with the advent of AI. AI's prospects in medicine are considerable and there is strong potential for AI within reproductive urology. Research in identifying the factors that can affect reproductive success either naturally or with assisted reproduction is of paramount importance to move the field forward.

Factors influencing variation in investigations after a negative CT brain scan in suspected subarachnoid haemorrhage: a qualitative study.

INTRODUCTION: Variation in the approach to the patient with a possible subarachnoid haemorrhage (SAH) has been previously documented. The purpose of this study was to identify factors that influence emergency physicians' decisions about diagnostic testing after a normal CT brain scan for ED patients with a headache suspicious of a SAH. METHODS: We conducted an interview-based qualitative study informed by social constructionist theory. Fifteen emergency physicians from six EDs across Queensland, Australia, underwent individual face-to-face or telephone interviews. Content analysis was performed whereby transcripts were examined and coded independently by two co-investigators, who then jointly agreed on the influencing factors. RESULTS: Six categories of influencing factors were identified. Patient interaction was at the forefront of the identified factors. This shared decision-making process incorporated 'what the patient wants' but may be biased by how the clinician communicates the benefits and harms of the diagnostic options to the patient. Patient risk profile, practice evidence and guidelines were also important. Other influencing factors included experiential factors of the clinician, consultation with colleagues and external influences where practice location and work processes impose constraints on test ordering external to the preferences of the clinician or patient. The six categories were organised within a conceptual framework comprising four components: the context, the evidence, the experience and the decision. CONCLUSIONS: When clinicians are faced with a diagnostic challenge, such as the workup of a patient with suspected SAH, there are a number of influencing factors that can result in a variation in approach. These need to be considered in approaches to improve the appropriateness and consistency of medical care.

Transferability of artificial neural networks for clinical document classification across hospitals: A case study on abnormality detection from radiology reports.

OBJECTIVE: Application of machine learning techniques for automatic and reliable classification of clinical documents have shown promising results. However, machine learning models require abundant training data specific to each target hospital and may not be able to benefit from available labeled data from each of the hospitals due to data variations. Such training data limitations have presented one of the major obstacles for maximising potential application of machine learning approaches in the healthcare domain. We investigated transferability of artificial neural network models across hospitals from different domains representing various age demographic groups (i.e., children, adults, and mixed) in order to cope with such limitations. MATERIALS AND METHODS: We explored the transferability of artificial neural networks for clinical document classification. Our case study was to detect abnormalities from limb X-ray reports obtained from the emergency department (ED) of three hospitals within different domains. Different transfer learning scenarios were investigated in order to employ a source hospital's trained model for addressing a target hospital's abnormality detection problem. RESULTS: A Convolutional Neural Network (CNN) model exhibited the best effectiveness compared to other networks when employing an embedding model trained on a large corpus of clinical documents. Furthermore, CNN models derived from a source hospital outperformed a conventional machine learning approach based on Support Vector Machines (SVM) when applied to a different (target) hospital. These models were further improved by leveraging available training data in target hospitals and outperformed the models that used only the target hospital data with F1-Score of 0.92-0.96 across three hospitals. DISCUSSION: Our transfer learning model used only simple vector representations of documents without any task-specific feature engineering. Transferring the CNN model significantly improved (approx.10% in F1-Score) the state-of-the-art approach for clinical document classification based on a trivial transferred model. In addition, the results showed that transfer learning techniques can further improve a CNN model that is trained only on either a source or target hospital's data. CONCLUSION: Transferring a pre-trained CNN model generated in one hospital to another facilitates application of machine learning approaches that alleviate both hospital-specific feature engineering and training data.