Polymer-based or Polymer-free Stents in Patients at High Bleeding Risk.

BACKGROUND: Polymer-free drug-coated stents provide superior clinical outcomes to bare-metal stents in patients at high bleeding risk who undergo percutaneous coronary intervention (PCI) and are treated with 1 month of dual antiplatelet therapy. Data on the use of polymer-based drug-eluting stents, as compared with polymer-free drug-coated stents, in such patients are limited. METHODS: In an international, randomized, single-blind trial, we compared polymer-based zotarolimus-eluting stents with polymer-free umirolimus-coated stents in patients at high bleeding risk. After PCI, patients were treated with 1 month of dual antiplatelet therapy, followed by single antiplatelet therapy. The primary outcome was a safety composite of death from cardiac causes, myocardial infarction, or stent thrombosis at 1 year. The principal secondary outcome was target-lesion failure, an effectiveness composite of death from cardiac causes, target-vessel myocardial infarction, or clinically indicated target-lesion revascularization. Both outcomes were powered for noninferiority. RESULTS: A total of 1996 patients at high bleeding risk were randomly assigned in a 1:1 ratio to receive zotarolimus-eluting stents (1003 patients) or polymer-free drug-coated stents (993 patients). At 1 year, the primary outcome was observed in 169 of 988 patients (17.1%) in the zotarolimus-eluting stent group and in 164 of 969 (16.9%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% confidence interval [CI], 3.5; noninferiority margin, 4.1; P = 0.01 for noninferiority). The principal secondary outcome was observed in 174 patients (17.6%) in the zotarolimus-eluting stent group and in 169 (17.4%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% CI, 3.5; noninferiority margin, 4.4; P = 0.007 for noninferiority). CONCLUSIONS: Among patients at high bleeding risk who received 1 month of dual antiplatelet therapy after PCI, use of polymer-based zotarolimus-eluting stents was noninferior to use of polymer-free drug-coated stents with regard to safety and effectiveness composite outcomes. (Funded by Medtronic; ONYX ONE ClinicalTrials.gov number, NCT03344653.).

Infant feeding practice and gastrointestinal tolerance: a real-world, multi-country, cross-sectional observational study.

BACKGROUND: Signs of feeding intolerance, such as gastrointestinal (GI) symptoms, are frequently observed in otherwise healthy formula-fed infants in the first months of life. The primary objective of this observational study was to examine GI tolerance in formula-fed infants (FFI) vs. breastfed infants (BFI) in a real-world setting with a secondary objective being the comparison of infants fed formula with pre- and/or probiotics (FFI_PP) and those fed formula without any pre- and/or probiotics (FFI_noPP) as well as BFI. METHODS: A six-country, cross-sectional study in full-term exclusively/predominantly FFI (n = 2036) and BFI (n = 760) aged 6-16 weeks was conducted using the validated Infant Gastrointestinal Symptom Questionnaire (IGSQ) and a Feeding Practice and Gut Comfort Questionnaire. RESULTS: The IGSQ composite score in FFI was non-inferior compared to BFI (mean difference [95%CI]: 0.17 [-0.34, 0.67]; non-inferiority p-value < 0.0001) and scores for BFI and FFI were below the threshold of 23, indicating no GI discomfort. Adjusted mean IGSQ scores ± SE were similar in FFI_PP (22.1 ± 0.2) and BFI (22.3 ± 0.3) while FFI_noPP (23.4 ± 0.3) was significantly higher and above 23 indicating some GI discomfort (mean differences [95%CI] FFI_noPP minus FFI_PP and FFI_noPP minus BFI were 1.28 [0.57, 1.98] and 1.09 [0.38, 1.80], respectively; both p < 0.01). Hard stools and difficulty in passing stool were more common in FFI compared to BFI (p < 0.01) but were less common in FFI_PP compared to FFI_noPP (p < 0.01). FFI_PP showed significantly less crying than FFI_noPP and was similar to BFI. Significantly fewer physician-confirmed colic episodes (Rome IV criteria) were reported in FFI_PP compared with FFI_noPP or BFI. CONCLUSIONS: In this real-world observational study, FFI had non-inferior overall GI tolerance compared to BFI. Within FFI, infants receiving formulas with pre- and/or probiotics had a better GI tolerance, improved stooling and less infantile colic compared to those receiving formula without any pre- and/or probiotics and were more similar to BFI. TRIAL REGISTRATION: NCT03703583, 12/10/2018 ( https://clinicaltrials.gov/ct2/show/NCT03703583 ).

Radical resection of lumbosacral lipomas in children: the Great Ormond Street Hospital experience.

PURPOSE: In 2009, Pang described a radical resection technique for congenital lumbosacral lipomas, with lower long-term symptomatic re-tethering rates compared with partial resections and conservative management, and low surgical morbidity. We adopted this technique in 2011, and aim to describe our first results. METHODS: In this monocentric retrospective audit, we included dorsal, transitional, chaotic, and caudal-type lumbosacral lipomas. Exclusion criteria were previously operated lipomas, pure filar lipomas, and concomitant major congenital anatomical urogenital/gastrointestinal abnormalities. Neuro-uro-orthopaedic status at presentation and at three months, one year and last postoperative follow-up, intraoperative electrophysiology, and extent of resection were collected. RESULTS: From January 2011 to September 2019, 91 patients were operated (median age 2y2m; 63 transitional; 14 caudal; 8 dorsal; 6 chaotic). Preoperatively, 67% were symptomatic. Preoperative and one-year postoperative rates of impaired ambulation (44% to 43%), hypoesthesia (8% to 5%), urodynamic/uroradiological abnormalities (49% to 37%), and foot/ankle deformities (8% to 5%) were comparable, whilst pain improved (25% to 5%) but catheterisation rates increased (21% to 36%). 23/92 (25%) suffered wound-related complications. 2/91 (2%) developed symptomatic re-tethering requiring second surgery. Mean cord/sac ratio was 0.47. 43% had > 20 mm3 residual fat, which improved with increasing surgical experience. CONCLUSION: Radical lipoma resection, guided by intraoperative neuromonitoring, with reconstruction of the neural placode and expansion duraplasty is technically feasible and results in low rates of late deterioration and re-tethering. Lipoma-type and pre-operative status are important outcome predictors. Operative risks are not insignificant. Future studies need to determine appropriate selection criteria for surgery.

New-Onset of Inflammatory Bowel Disease in a Patient Treated With Teprotumumab for Thyroid Associated Ophthalmopathy.

A patient with thyroid-associated ophthalmopathy was treated with teprotumumab and developed symptoms concerning for inflammatory bowel disease after her sixth infusion. Colonoscopy was performed, and mucosal biopsies identified evidence of active colitis consistent with a diagnosis of ulcerative colitis. Despite treatment with budesonide and mesalamine, the patient continued to be symptomatic one and a half months after cessation of teprotumumab and required infliximab to achieve good control of her inflammatory bowel disease. This case represents the first report of new-onset inflammatory bowel disease arising during treatment with teprotumumab.

Micronutrient-fortified infant cereal improves Hb status and reduces iron-deficiency anaemia in Indian infants: an effectiveness study.

Anaemia affects approximately 69 % of Indian children aged 6-12 months, with Fe deficiency (ID) being a common cause. The effectiveness of micronutrient-fortified infant cereal in improving Fe status and neurodevelopment was evaluated in non-anaemic and mildly anaemic Indian infants. An intervention group (IC) enrolled at age 6 months consumed 50 g/d of rice-based cereal providing 3·75 mg Fe/d as ferrous fumarate for 6 months (n 80) and was compared with a matched static cross-sectional control group (CG) without intervention enrolled at age 12 months (n 80). Mean Hb was higher in IC (118·1 (sd 10·2) g/l) v. CG (109·5 (sd 16·4) g/l) at age 12 months (adjusted mean difference: 9·7 g/l; 95 % CI 5·1, 14·3; P < 0·001), while geometric mean serum ferritin tended to be higher (27·0 (-1 sd 13·4, +1 sd 54·4) v. 20·3 (-1 sd 7·5, +1 sd 55·0) ng/ml); P = 0·085) and soluble transferrin receptor was lower (1·70 (-1 sd 1·19, +1 sd 2·43) v. 2·07 (-1 sd 1·29, +1 sd 3·33) mg/l; P = 0·014). Anaemia (23 v. 45 %; P = 0·007) and ID (17 v. 40 %; P = 0·003) were lower in IC v. CG. Bayley Scales of Infant and Toddler Development Third Edition scores for language (P = 0·003), motor development (P = 0·018), social-emotional (P = 0·004) and adaptive behaviour (P < 0·001), but not cognitive development (P = 0·980), were higher in IC v. CG. No significant difference in anthropometric Z-scores was observed between the groups. Consuming a micronutrient-fortified infant cereal daily for 6 months during complementary feeding promoted better Fe status while reducing the risk for anaemia and ID and was associated with superior neurodevelopmental scores.

Intraoperative neurophysiological monitoring in paediatric Chiari surgery-help or hindrance?

INTRODUCTION: The role of intraoperative neurophysiological monitoring (IONM) during surgery for Chiari I malformation has not been fully elucidated. Questions remain regarding its utility as an adjunct to foramen magnum decompression surgery, specifically, does IONM improve the safety profile of foramen magnum decompression surgery and can IONM parameters help in intraoperative surgical decision-making. This study aimed to describe a single institution experience of IOM during paediatric Chiari I surgery. METHODS: The methodology comprised a retrospective review of prospectively collected electronic neurosurgical departmental operative database. Inclusion criteria were children under 16 years of age who had undergone foramen magnum decompression for Chiari I malformation with IONM. In addition to basic demographic data, details pertaining to presenting features and post-operative outcomes were obtained. These included primary symptoms of Chiari I malformation and indications for surgery. MRI findings, including the presence of syringomyelia on pre-and post-operative imaging, were reviewed. Details of the surgical technique for each patient were recorded. Only patients with either serial brainstem auditory evoked potential (BAEP) and/or upper limb somatosensory evoked potential (SSEP) recordings were included. Two time points were used for the purposes of analysing IONM data; initial baseline before skin incision and final at the time of skin closure. RESULTS: Thirty-seven children underwent foramen magnum decompression (FMD) with IONM. Mean age was 10.5 years (range 1-16 years) with a male:female ratio 13:24. The commonest clinical features on presentation included headaches (15) and scoliosis (13). Twenty-four patients had evidence of associated syringomyelia (24/37 = 64.9%). A reduction in the SSEP latency was observed in all patients. SSEP amplitude was more variable, with a decrease seen in 18 patients and an increase observed in 12 patients. BAEP recordings decreased in 13 patients and increased in 4 patients. There were no adverse neurological events following surgery; the primary symptom was resolved or improved in all patients at 3-month follow-up. Resolution or improvement in syringomyelia was observed in 19/24 cases. CONCLUSIONS: Our data shows that FMD for Chiari malformation (CM) is associated with changes in SSEPs and BAEPs. However, we did not identify a definite link between clinical outcomes and IONM, nor did syrinx outcome correlate with IONM. There may be a role for IONM in CM surgery but more robust data with better-defined parameters are required to further understand the impact of IONM in CM surgery.

First detection of Echinococcus multilocularis in Croatia.

Echinococcus multilocularis has been spreading through Europe but has not yet been reported in Croatia. We report the results of a surveillance programme to detect E. multilocularis in red foxes (Vulpes vulpes) in different parts of Croatia. PCR-based screening of faecal samples from 238 red foxes in 2015 and 150 in 2016 indicate prevalences of 7.5% in 2015 and 6.6% in 2016 (overall 7.2%, CI 4.9 to 10.3). Positive samples were confirmed by sequencing parts of the nad1 gene and the gene encoding mitochondrial 12S rRNA. Geographic locations of all examined and positive cases were mapped to provide data on the distribution of E. multilocularis. Our results provide the first detection of E. multilocularis in Croatia and extend the southern boundary of this parasite's endemic area.

Genome-wide association studies in diverse populations.

Genome-wide association (GWA) studies have identified a large number of SNPs associated with disease phenotypes. As most GWA studies have been performed in populations of European descent, this Review examines the issues involved in extending the consideration of GWA studies to diverse worldwide populations. Although challenges exist with issues such as imputation, admixture and replication, investigation of a greater diversity of populations could make substantial contributions to the goal of mapping the genetic determinants of complex diseases for the human population as a whole.

Evaluation of ELISA for the detection of rabies virus antibodies from the thoracic liquid and muscle extract samples in the monitoring of fox oral vaccination campaigns.

BACKGROUND: The main goal of oral vaccination of foxes is eradication of rabies in the red fox population as rabies reservoirs. To evaluate the success of vaccination a serological testing is conducted as a part of monitoring program. Two different methods are used regarding rabies serology: virus neutralisation test and ELISA. METHODS: In this study the reliability of BioPro ELISA was evaluated for testing haemolytic thoracic liquids and muscle extracts originated from 147 foxes in comparison to mFAVN. Also, the influence of heat treatment of samples on test results was investigated. RESULTS: The specificity of the test for not-heat treated samples was 92.98% and sensitivity 79.20%. Diagnostic validity of the ELISA compared to the mFAVN test when not-heat treated samples were used was 89.16%. The specificity of the test for heat treated samples was 79.10% and sensitivity 96.36%. Diagnostic validity of the BioPro ELISA compared to the mFAVN test for heat treated samples was 94.30%. CONCLUSION: According to this study, the BioPro ELISA is reliable tool for detection of rabies specific antibodies in the context of evaluation of oral vaccination of foxes from poor quality samples as a substitution for virus neutralisation tests.

The effect of substituents on the surface modification of anatase nanoparticles with catecholate-type ligands: a combined DFT and experimental study.

The surface modification of nanocrystalline TiO2 particles (45 Å) with catecholate-type ligands having different electron donating/electron withdrawing substituent groups, specifically 3-methylcatechol, 4-methylcatechol, 3-methoxycatechol, 3,4-dihydroxybenzaldehyde and 4-nitrocatechol, was found to alter the optical properties of nanoparticles in a similar way to catechol. The formation of the inner-sphere charge-transfer (CT) complexes results in a red shift of the semiconductor absorption compared to unmodified nanocrystallites and a reduction of the effective band gap, being slightly less pronounced in the case of electron withdrawing substituents. The investigated ligands have the optimal geometry for binding to surface Ti atoms, resulting in ring coordination complexes of the catecholate type (binuclear bidentate binding-bridging) thus restoring six-coordinated octahedral geometry of surface Ti atoms. From the absorption measurements (Benesi-Hildebrand plot), the stability constants in methanol/water = 90/10 solutions at pH 2 in the order of 10(3) M(-1) have been determined. The binding structures were investigated by using FTIR spectroscopy. Thermal stability of CT-complexes was investigated by using TG/DSC/MS analysis. Quantum chemical calculations on model systems using density functional theory (DFT) were performed to obtain the vibrational frequencies of charge transfer complexes, and the calculated values were compared with the experimental data.

Session Introduction: Artificial Intelligence in Clinical Medicine: Generative and Interactive Systems at the Human-Machine Interface.

Artificial Intelligence (AI) models are substantially enhancing the capability to analyze complex and multi-dimensional datasets. Generative AI and deep learning models have demonstrated significant advancements in extracting knowledge from unstructured text, imaging as well as structured and tabular data. This recent breakthrough in AI has inspired research in medicine, leading to the development of numerous tools for creating clinical decision support systems, monitoring tools, image interpretation, and triaging capabilities. Nevertheless, comprehensive research is imperative to evaluate the potential impact and implications of AI systems in healthcare. At the 2024 Pacific Symposium on Biocomputing (PSB) session entitled "Artificial Intelligence in Clinical Medicine: Generative and Interactive Systems at the Human-Machine Interface", we spotlight research that develops and applies AI algorithms to solve real-world problems in healthcare.

Association between Exposure to Leptospira spp. and Abortion in Mares in Croatia.

Leptospirosis is one of the most common zoonotic infections and a major problem in terms of both veterinary medicine and public health. However, the disease is under-recognised and under-diagnosed worldwide, particularly in horses. Clinical leptospirosis in horses is mainly associated with recurrent uveitis (ERU), which has recently been studied more intensively, and reproductive disorders, the epidemiology of which is still relatively poorly understood. To enhance our comprehension of abortions caused by leptospirosis in horses and to identify the causative strains, a serological study was carried out with subsequent molecular characterisation of the isolate obtained. Using the microscopic agglutination test (MAT), serum samples from mares that aborted and foetal fluids (when available) were tested for antibodies against Leptospira spp. Furthermore, bacteria isolation from kidney cultures was conducted. Of 97 mare serum samples, 21 (21.64%) tested positive, with Grippotyphosa and Pomona being the most frequently detected serogroups. A significantly higher seroprevalence was found in aborting mares compared to the healthy horse population from the same geographical area, as well as a pronounced seasonal variation. Leptospiral antibodies were not detected in any of the foetal fluids, but isolation was successful in 1 case out of 39 (2.56%). Genotyping by multilocus sequence typing (MLST) and core genome multilocus sequence typing (cgMLST) identified the obtained isolate as Leptospira kirschneri, serogroup Pomona, serovar Mozdok. Further surveillance and molecular typing of Leptospira strains causing abortion in horses would be invaluable in understanding the prevalence and impact of leptospirosis on equine reproductive health in Europe.

Large Anthrax Outbreak in a New Locality in Croatia, 2022.

Bacillus anthracis is a well-known zoonotic pathogen that can cause disease in both animals and humans. Moreover, it has a high bioterrorism potential as its lethal spores are resistant to inactivation, are easy to produce in large quantities, and are easily spread over large areas. Anthrax cases occur in different parts of the world, including most European countries. Specific areas of Croatia are long known as anthrax districts, but with sporadically reported cases over the years. Here, we present a major outbreak of animal and human anthrax in the region of Lonjsko Polje in Croatia, a region not known to have anthrax cases in the past. The outbreak started in July 2022 and lasted several months, but most human and animal cases were reported in the first month. During the outbreak, there were 17 reported human cases of cutaneous anthrax and 29 laboratory-confirmed animal cases. However, due to issues in reporting in animals and the late finding of the carcasses, which made laboratory diagnostics challenging, the actual number of animal cases was probably significantly higher.

Association of the Achondroplasia Foramen Magnum Score and intraoperative neuromonitoring.

INTRODUCTION: Foramen magnum stenosis in achondroplasia carries a risk of sudden death. A proportion of these patients benefit from foramen magnum decompression (FMD). The Achondroplasia Foramen Magnum Score (AFMS) was developed to stratify those most at risk. We hypothesise that this score may be reflected in neurophysiological findings. METHODS: Patients with achondroplasia who had undergone FMD (n=20) were retrospectively grouped into AFMS 2, 3 and 4. Amplitude from tibialis anterior (TA) and the percentage change in somatosensory evoked potential (SSEP) latency after FMD were reported. RESULTS: Baseline motor evoked potential amplitudes for patients with AFMS=4 were significantly lower left (p=0.0017 and p=0.02 for right and left TA, respectively) compared with AFMS grades 2 and 3. Median reduction (% change) in SSEP latency (ms) after surgery was not significantly different in any of the patients. CONCLUSIONS: This short report cross-references AFMS to intraoperative neuromonitoring. Baseline amplitudes were noticeably lower in the most severe AFMS group. This observation supports the notion that AFMS can help risk stratify patients and aid in surgical selection.

Galacto-oligosaccharide preconditioning improves metabolic activity and engraftment of Limosilactobacillus reuteri and stimulates osteoblastogenesis ex vivo.

A probiotic-related benefit for the host is inherently linked to metabolic activity and integration in the gut ecosystem. To facilitate these, probiotics are often combined with specific prebiotics in a synbiotic formulation. Here, we propose an approach for improving probiotic metabolic activity and engraftment. By cultivating the probiotic strain in the presence of a specific prebiotic (preconditioning), the bacterial enzymatic machinery is geared towards prebiotic consumption. Today, it is not known if preconditioning constitutes an advantage for the synbiotic concept. Therefore, we assessed the effects galacto-oligosaccharide (GOS) addition and preconditioning on GOS of Limosilactobacillus reuteri DSM 17938 on ex vivo colonic metabolic profiles, microbial community dynamics, and osteoblastogenesis. We show that adding GOS and preconditioning L. reuteri DSM 17938 act on different scales, yet both increase ex vivo short-chain fatty acid (SCFA) production and engraftment within the microbial community. Furthermore, preconditioned supernatants or SCFA cocktails mirroring these profiles decrease the migration speed of MC3T3-E1 osteoblasts, increase several osteogenic differentiation markers, and stimulate bone mineralization. Thus, our results demonstrate that preconditioning of L. reuteri with GOS may represent an incremental advantage for synbiotics by optimizing metabolite production, microbial engraftment, microbiome profile, and increased osteoblastogenesis.

Retrospective analysis of sero-prevalence and bait uptake estimations in foxes after oral rabies vaccination programmes at European level: Lessons learned and paths forward.

Rabies caused by the Classical Rabies Virus (Lyssavirus rabies abbreviated RABV) in the European Union has been close to elimination mainly thanks to Oral Rabies Vaccination (ORV) campaigns targeting wildlife (primarily red foxes). ORV programmes co-financed by the European Commission include a monitoring-component to assess the effectiveness of the ORV campaigns at national level. This assessment is performed by a random collection of red foxes in the vaccinated areas with control of antibodies presence by serological analysis and control of bait uptake by detection of biomarkers (tetracycline incorporated into the baits) in the bones and teeth. ORV programmes aim to a vaccine coverage high enough to immunize (ideally) 70 % of the reservoir population to control the spread of the disease. European Union (EU) programmes that led to almost elimination of rabies on the territory have been traditionally found to have a bait uptake average of 70 % (EU countries; 2010-2020 period) while the seroconversion data showed an average level of 40 % (EU countries; 2010-2020 period). To better understand variations of these indicators, a study was been set up to evaluate the impact of several variables (linked to the vaccination programme itself and linked to environmental conditions) on the bait uptake and the seroconversion rate. Thus, pooling data from several countries provides more powerful statistics and the highest probability of detecting trends. Results of this study advocate the use of a single serological test across the EU since data variation due to the type of test used was higher than variations due to field factors, making the interpretation of monitoring results at EU level challenging. In addition, the results indicates a negative correlation between bait uptake and maximum temperatures reached during ORV campaigns questioning the potential impact of climatic change and associated increase of temperatures on the ORV programmes efficiency. Several hypotheses requesting additional investigation are drawn and discussed in this paper.

Limosilactobacillus reuteri DSM 17938-Containing Infant Formulas and the Associations with Gastrointestinal Tolerance: A Cross-Sectional Observational Study.

Limosilactobacillus (L.; previously Lactobacillus) reuteri has been shown to influence gastrointestinal (GI) tolerance. This study was a secondary analysis of GI tolerance data from a multi-country, cross-sectional, observational study in healthy infants using the validated Infant Gastrointestinal Symptom Questionnaire (IGSQ) and a gut comfort questionnaire. Breastfed infants (BFI; n = 760) were compared to formula-fed infants receiving either L. reuteri-containing formula (FFI + LR; n = 470) or standard formula without any probiotic or prebiotic (FFI-Std; n = 501). The IGSQ composite scores (adjusted mean ± SE) in FFI + LR (22.17 ± 0.39) was significantly lower than in FFI-Std (23.41 ± 0.37) and similar to BFI (22.34 ± 0.30;), indicating better GI tolerance in FFI + LR than in FFI-Std. Compared with FFI-Std, FFI + LR had lower reports of difficulty in passing stools (11% vs. 22%; adjusted-odds ratio (OR) (95%CI) = 0.46 (0.31-0.68)), fewer hard stools (mean difference = -0.12 (-0.21, -0.02)) and less physician-confirmed colic (OR = 0.61 (0.45-0.82)), and similar to BFI. Parent-reported crying time (mean difference = -0.15 (-0.28, -0.01)), frequency of spitting-up/vomiting (mean difference = -0.18 (-0.34, -0.03)), volume of spit-up (mean difference = -0.20 (-0.32, -0.08)) and fussiness due to spitting-up/vomiting (mean difference = -0.17 (-0.29, -0.05)) were lower in FFI + LR versus FFI-Std and similar to BFI. In this study, L. reuteri-containing formula was associated with improved digestive tolerance and behavioral patterns.

Coxiella burnetii (Q-fever) outbreak associated with non-occupational exposure in a semi-urban area of western Croatia in 2022.

In March 2022, an outbreak of Q fever (Coxiella burnetii) with non-occupational exposure was confirmed in a semi-urban area in Cavle, Croatia. Veterinary and human epidemiological investigations were conducted to identify the source of the outbreak and to implement appropriate control measures. Three farms were settled next to each other near the homes of the first human cases at the end of the street. The closest farm was less than 500 meters away. These farms contained 161 adult sheep and goats. Among the animal samples analysed, all 16 goats (100%) and 24/50 sheep (48%) tested positive for C. burnetii IgM/IgG antibodies, phase I and II. One out of five sheeps' vaginal swabs were C. burnetti DNA positive. Human testing revealed 20 confirmed and three probable cases (9/23 pneumonia, 2/23 hepatitis, 21/23 fever), with three hospitalizations, and one death. Twenty-seven cases were discarded following negative laboratory results. The epidemiological investigation revealed airborne transmission as the most likely route of transmission. Multiple logistic regression analyses were used to evaluate risk factors for Q fever infection. Persons who were near the farms (≤750 m) (OR 4.5; 95% CI = 1.1-18.3) and lived in the nearest street to the farms had the highest risk of contracting Q fever (OR 3.7; 95% CI = 1.1-13.6). Decreased rainfall compared to monthly averages was recorded in the months prior to the outbreak with several days of strong wind in January preceding the outbreak. This was the largest Q fever outbreak in the county in the last 16 years, which was unexpected due to its location and non-occupational exposure. To stop the outbreak, numerous intensive biosecurity measures were implemented. The outbreak highlights the importance of urban development strategies to limit the number of animal housing near residential areas while providing regular biosecurity measures to prevent infections in livestock.

Clinical Recommender Algorithms to Simulate Digital Specialty Consultations.

Advances in medical science simultaneously benefit patients while contributing to an over-whelming complexity of medicine with a decision space of thousands of possible diagnoses, tests, and treatment options. Medical expertise becomes the most important scarce health-care resource, reflected in tens of millions in the US alone with deficient access to specialty care. Combining the growing wealth of electronic medical record data with modern recommender algorithms has the potential to synthesize the clinical community's expertise into an executable format to manage this information overload and improve access to personalized care suggestions. We focus here specifically on outpatient consultations for (Endocrine) specialty expertise, one of the highest demand and most amenable areas for electronic consultation systems. Specifically we develop and evaluate models to predict the clinical orders of these initial specialty referral consultations using an ensemble of feed-forward neural networks as compared to multiple baseline algorithms. As benchmarks closer to the existing standard of care, we used diagnosis-based clinical checklists based on our review of literature and practice guidelines (e.g., Up-to-Date) for each common referral diagnosis as well as existing electronic consult referral guides. Results indicate that such automated algorithms trained on historical data can provide more personalized decision support with greater accuracy than existing benchmarks, with the potential to power fully digital consultation services that could consolidate utilization of scarce medical expertise, improving consistency of quality and access to care for more patients.