Association between body mass index and multigland primary hyperparathyroidism.

INTRODUCTION: Multigland disease (MGD) accounts for 15% of sporadic primary hyperparathyroidism (pHPT). Several studies have reported a link between obesity and calcium metabolism (e.g., increased incidence of pHPT, higher levels of parathyroid hormone, lower vitamin D levels, and larger parathyroid glands). Obese patients have also been shown to require reoperation for persistent/recurrent pHPT more often than nonobese controls. We hypothesize that obese patients may have a higher prevalence of MGD. METHODS: This was a retrospective review of a prospectively collected parathyroid database that included adult patients with sporadic pHPT, who underwent initial parathyroidectomy between 1999 and 2013. Demographic, clinicopathologic, operative, and laboratory data were assessed for associations with MGD. RESULTS: Of 1305 consecutive patients, 200 (15%) had MGD. Median age was 59 y. Univariate analyses demonstrated that MGD was associated with age > 60 y, higher body mass index (BMI), history of lithium therapy, lower 24-h urine calcium excretion, higher serum alkaline phosphatase levels, and smaller size of the first excised parathyroid gland. On multivariate analyses, predictors of MGD were BMI 30-39.9 kg/m(2) (odds ratio [OR] 1.5; 95% confidence interval [CI] 1.2-2.5), BMI ≥ 40 kg/m(2) (OR 1.8; 95% CI 1.3-3.1), and smaller size of the first excised parathyroid (OR 0.7; 95% CI 0.6-0.8). CONCLUSIONS: This study demonstrates a higher incidence of MGD in obese and morbidly obese patients. Due to a higher risk of MGD, surgeons should have a lower threshold to perform bilateral exploration in obese patients, especially if the first excised parathyroid gland is relatively small.

The Effect of Thyroiditis on the Yield of Central Compartment Lymph Nodes in Patients with Papillary Thyroid Cancer.

BACKGROUND: In patients who have undergone thyroidectomy and central compartment neck dissection (CCND) for papillary thyroid cancer (PTC), visualization of enlarged lymph nodes may lead to more extensive CCND. This study sought to determine the effect of patient age and the presence of thyroiditis on the number of malignant and total lymph nodes resected in patients who underwent CCND for PTC. METHODS: This retrospective review examined a prospective database of patients who underwent total thyroidectomy and CCND for PTC between April 2009 and June 2013 and had thyroiditis on the final pathology. The patients were categorized into age groups by decade (18-29, 30-39, 40-49, 50-59, and ≥60 years) and compared with a control group of patients matched by age, gender, and tumor size. RESULTS: Of 74 patients with thyroiditis, 64 (87 %) were women. The median age of the patients was 47.5 years (range 18.2-72.0 years). The patients with thyroiditis had more lymph nodes resected than those without thyroiditis (median 11 vs 7; p < 0.01). However, these patients had fewer malignant lymph nodes (median 0 vs 1.5; p = 0.06), resulting in a lower lymph node ratio (0 vs 0.18; p = 0.02) for the entire cohort, but particularly for the youngest (18-29 years) and oldest (≥60 years) age groups. CONCLUSIONS: Patients with thyroiditis and PTC who underwent CCND had more lymph nodes resected but a had lower proportion of metastatic lymph nodes than those without thyroiditis. Given the relatively low yield of malignant cervical lymphadenopathy, a more judicious approach to CCND might be considered, particularly for the youngest and oldest patients with PTC and thyroiditis.

Longitudinal cohort study investigating neurodevelopmental and socioemotional outcomes in school-entry aged children after open heart surgery in Australia and New Zealand: the NITRIC follow-up study protocol.

INTRODUCTION: Despite growing awareness of neurodevelopmental impairments in children with congenital heart disease (CHD), there is a lack of large, longitudinal, population-based cohorts. Little is known about the contemporary neurodevelopmental profile and the emergence of specific impairments in children with CHD entering school. The performance of standardised screening tools to predict neurodevelopmental outcomes at school age in this high-risk population remains poorly understood. The NITric oxide during cardiopulmonary bypass to improve Recovery in Infants with Congenital heart defects (NITRIC) trial randomised 1371 children <2 years of age, investigating the effect of gaseous nitric oxide applied into the cardiopulmonary bypass oxygenator during heart surgery. The NITRIC follow-up study will follow this cohort annually until 5 years of age to assess outcomes related to cognition and socioemotional behaviour at school entry, identify risk factors for adverse outcomes and evaluate the performance of screening tools. METHODS AND ANALYSIS: Approximately 1150 children from the NITRIC trial across five sites in Australia and New Zealand will be eligible. Follow-up assessments will occur in two stages: (1) annual online screening of global neurodevelopment, socioemotional and executive functioning, health-related quality of life and parenting stress at ages 2-5 years; and (2) face-to-face assessment at age 5 years assessing intellectual ability, attention, memory and processing speed; fine motor skills; language and communication; and socioemotional outcomes. Cognitive and socioemotional outcomes and trajectories of neurodevelopment will be described and demographic, clinical, genetic and environmental predictors of these outcomes will be explored. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Children's Health Queensland (HREC/20/QCHQ/70626) and New Zealand Health and Disability (21/NTA/83) Research Ethics Committees. The findings will inform the development of clinical decision tools and improve preventative and intervention strategies in children with CHD. Dissemination of the outcomes of the study is expected via publications in peer-reviewed journals, presentation at conferences, via social media, podcast presentations and medical education resources, and through CHD family partners. TRIAL REGISTRATION NUMBER: The trial was prospectively registered with the Australian New Zealand Clinical Trials Registry as 'Gene Expression to Predict Long-Term Neurodevelopmental Outcome in Infants from the NITric oxide during cardiopulmonary bypass to improve Recovery in Infants with Congenital heart defects (NITRIC) Study - A Multicentre Prospective Trial'. TRIAL REGISTRATION: ACTRN12621000904875.

Tailoring the behavior of optical microcavities with high refractive index sol-gel coatings.

Silica optical resonators with high quality factors, small mode volumes, and high refractive index contrast are desirable in many applications throughout the fundamental and applied sciences. However, these parameters are not easily modified in plain silica devices. In the present work, we theoretically and experimentally demonstrate the use of high refractive index sol-gel coatings to achieve a significant reduction in mode volume of silica toroids while maintaining high quality factors. In addition to tuning the mode volume, the presence of the coating changes both the location and shape of the optical field.

Biomechanical analysis of stacked plating techniques to stabilize distal radial fractures in small dogs.

OBJECTIVE: To evaluate the fatigue life of partially stacked and fully stacked (1.5/2.0 and 2.0/2.7 mm) veterinary cuttable plates (VCP) in a fracture gap model of the distal aspect of the radius. STUDY DESIGN: In vitro biomechanical study. METHODS: Constructs (n=4/group) were assembled for each of 8 groups using 8-hole plates (1.5/2.0 and 2.0/2.7 mm VCP) in the following configurations: unstacked; 2-hole stacked centered over the gap (COG); 4-hole stacked COG; and fully stacked. Plate(s) were secured to 2 separate polyvinylchloride pipe lengths, mounted to a mechanical testing system with a custom jig, and were loaded in axial compression for 10(6) cycles at 10 Hz or until failure at 6-60 N for the 1.5/2.0 mm VCP and 10-100 N for the 2.0/2.7 mm VCP. Differences in number of cycles, stiffness, and failure mode were recorded. RESULTS: All construct failures occurred through a screw hole adjacent to the gap. Fully stacked and 4-hole stacked 1.5/2.0 and 2.0/2.7 mm VCP withstood 10(6) cycles. Fatigue life and stiffness of the 1.5/2.0 or 2.0/2.7 mm unstacked constructs were significantly less than the other constructs. Differences were identified in stiffness among the 1.5/2.0 mm stacked constructs and in fatigue life among the 2.0/2.7 mm VCP stacked constructs. CONCLUSION: Four-hole partially stacked VCP (either 1.5/2.0 or 2.0/2.7 mm) have comparable mechanical properties to fully stacked VCP. CLINICAL RELEVANCE: Partial stacking of 2 holes of VCP on both sides of the fracture gap may provide sufficient strength for healing, but this premise must be tested in vivo.

"How long will I continue to be normal?" Adults with a Fontan circulation's greatest concerns.

BACKGROUND: Little is known about adults living with a Fontan circulation's concerns outside the scope of their clinical outcomes. We examined adults with a Fontan circulations' greatest concerns, as well as their concerns around anti-coagulation, pregnancy and finances. METHODS: Adults with a Fontan circulation in the Australian and New Zealand Fontan Registry were invited to complete an anonymous online survey, of which 57 participated. A qualitative method approach using thematic analyses was used. RESULTS: The greatest concerns for adults living with a Fontan circulation were fear of death/uncertainty around life expectancy which for many individuals colored their concerns around physical health, pregnancy and having children, quality of life and finances. Improving information about outcomes to patients with a Fontan circulation might alleviate uncertainties about their future. CONCLUSIONS: Fear of death is the primary concern of adults with a Fontan circulation. It may require improved communication and targeted psychological interventions. Physical exercise incorporated as part of their lifestyle should be encouraged to alleviate physical concerns and also improve psychological well-being.

"Will she live a long happy life?" Parents' concerns for their children with Fontan circulation.

BACKGROUND: Families of children at the worst end of the congenital heart disease endure a significant burden which is often not clearly delineated in the clinical literature. We examined the greatest concerns of parents whose children have a Fontan circulation. METHODS: Parents (N = 107) of children in the Australian and New Zealand Fontan Registry completed online surveys with open-ended and closed questions. A qualitative method approach incorporating thematic analyses was used. RESULTS: The greatest concerns for parents of a child with a Fontan circulation were centered on fear of death for their child and psychosocial well-being, followed by lesser themes around anti-coagulation use, pregnancy and financial burdens. CONCLUSIONS: Fear of death and the psychological well-being of their children were the main parental concerns. It highlights the need to clearly communicate information on outcomes to families, and the need for family-focused psychological interventions to improve the psychosocial functioning of both parents and young people.

Snowball Earth climate dynamics and Cryogenian geology-geobiology.

Geological evidence indicates that grounded ice sheets reached sea level at all latitudes during two long-lived Cryogenian (58 and ≥5 My) glaciations. Combined uranium-lead and rhenium-osmium dating suggests that the older (Sturtian) glacial onset and both terminations were globally synchronous. Geochemical data imply that CO2 was 102 PAL (present atmospheric level) at the younger termination, consistent with a global ice cover. Sturtian glaciation followed breakup of a tropical supercontinent, and its onset coincided with the equatorial emplacement of a large igneous province. Modeling shows that the small thermal inertia of a globally frozen surface reverses the annual mean tropical atmospheric circulation, producing an equatorial desert and net snow and frost accumulation elsewhere. Oceanic ice thickens, forming a sea glacier that flows gravitationally toward the equator, sustained by the hydrologic cycle and by basal freezing and melting. Tropical ice sheets flow faster as CO2 rises but lose mass and become sensitive to orbital changes. Equatorial dust accumulation engenders supraglacial oligotrophic meltwater ecosystems, favorable for cyanobacteria and certain eukaryotes. Meltwater flushing through cracks enables organic burial and submarine deposition of airborne volcanic ash. The subglacial ocean is turbulent and well mixed, in response to geothermal heating and heat loss through the ice cover, increasing with latitude. Terminal carbonate deposits, unique to Cryogenian glaciations, are products of intense weathering and ocean stratification. Whole-ocean warming and collapsing peripheral bulges allow marine coastal flooding to continue long after ice-sheet disappearance. The evolutionary legacy of Snowball Earth is perceptible in fossils and living organisms.

Antipsychotics produce locomotor impairment in larval zebrafish.

Zebrafish has been a favored vertebrate genetic model organism for studying developmental processes. It also holds a great potential for understanding the genetic basis of behavior and associated behavioral disorders. Despite such potential, their use in the study of behavior is greatly under-explored. It is well known that multiple classes of drugs used to treat psychiatric diseases produce extrapyramidal side (EPS) effects and consequent movement disorders in humans. The underlying molecular causes of these drug-induced movement disorders are poorly understood. Here we report that zebrafish treated with the antipsychotics fluphenazine and haloperidol (both of which can induce severe EPS in humans) develop movement defects. In contrast, another antipsychotic olanzapine, which produces mild to little EPS in humans, leads to minimal movement defects in zebrafish. These results establish a rapid assay system in which the effects of EPS-inducing agents can be assessed. Thus, future genetic screening in zebrafish shall identify genes and pathways that elucidate drug-induced movement disorder in human as well as provide insights into the brain control of locomotor activity. Future chemical screening in zebrafish may act as a preclinical test for the EPS effect of certain drugs, as well as a test used to researching drugs made to counteract the effects of EPS.

The tropical rain belts with an annual cycle and a continent model intercomparison project: TRACMIP.

This paper introduces the Tropical Rain belts with an Annual cycle and a Continent Model Inter-comparison Project (TRACMIP). TRACMIP studies the dynamics of tropical rain belts and their response to past and future radiative forcings through simulations with 13 comprehensive and one simplified atmosphere models coupled to a slab ocean and driven by seasonally varying insolation. Five idealized experiments, two with an aquaplanet setup and three with a setup with an idealized tropical continent, fill the space between prescribed-SST aquaplanet simulations and realistic simulations provided by CMIP5/6. The simulations reproduce key features of present-day climate and expected future climate change, including an annual-mean intertropical convergence zone (ITCZ) that is located north of the equator and Hadley cells and eddy-driven jets that are similar to present-day climate. Quadrupling CO2 leads to a northward ITCZ shift and preferential warming in Northern high latitudes. The simulations show interesting CO2-induced changes in the seasonal excursion of the ITCZ and indicate a possible state dependence of climate sensitivity. The inclusion of an idealized continent modulates both the control climate and the response to increased CO2; for example, it reduces the northward ITCZ shift associated with warming and, in some models, climate sensitivity. In response to eccentricity-driven seasonal insolation changes, seasonal changes in oceanic rainfall are best characterized as a meridional dipole, while seasonal continental rainfall changes tend to be symmetric about the equator. This survey illustrates TRACMIP's potential to engender a deeper understanding of global and regional climate and to address questions on past and future climate change.

Osteosarcoma at the site of a triple pelvic osteotomy in a dog.

An osteosarcoma (OSA) involving the right pelvis was diagnosed in a 12-year-old golden retriever 11 years after triple pelvic osteotomy (TPO) surgery. The dog was presented with a 12-week history of nonweight-bearing lameness of the right hind limb. Radiographs demonstrated an aggressive bone lesion of the right ilium with profound periosteal proliferation and punctate lysis that extended along the ilium caudally and into the right ischium, with its epicenter at the level of the right TPO plate. Necropsy revealed that the entire right hemipelvis, especially the ischium, was markedly thickened and firm with irregular margins. Histopathology was consistent with a diagnosis of OSA.

High-dose 131I-metaiodobenzylguanidine therapy for 12 patients with malignant pheochromocytoma.

BACKGROUND: 131I-Metaiodobenzylguanidine (131I-MIBG) can be used systemically to treat malignant pheochromocytoma. To improve outcome, the authors used higher levels of activity of 131I-MIBG than previously reported. The authors reported the response rates and toxicity levels in patients with malignant pheochromocytoma or paraganglioma who were treated with high-dose 131I-MIBG. METHODS: Following debulking surgery and stem cell harvest, 12 patients with malignant pheochromocytoma or paraganglioma were treated with 131I-MIBG. Five had received previous external beam radiation and/or chemotherapy. The median single treatment dose was 800 mCi (37 gigabecquerels; range, 386-866 mCi) or 11.5 mCi/kg (range, 5.6-18.3 mCi/kg). The median cumulative dose was 1015 mCi (range, 386-1690 mCi). RESULTS: Three patients had a complete response, two of whom had soft tissue and skeletal metastases. Their median follow-up was 45 months (range, 23-101 months). Seven patients had a partial response (PR), with a median follow-up 43 months (range, 6-47 months). Two patients without a response died with progressive disease (PD) and 2 patients with an initial PR died of PD at 13 and 11 months, respectively. Grade 3 thrombocytopenia occurred after 79% (15 of 19) of treatments had been administered. Grade 3 and 4 neutropenia followed 53% (10 of 19) and 19% (4 of 19) of treatments, respectively. One patient required stem cell infusion, and one developed primary ovarian failure. CONCLUSIONS: The single and cumulative doses of 131I-MIBG were approximately 2-3.5 times higher than those used at other centers. Unlike previous reports, two patients with both skeletal and soft tissue metastases had a complete response. Hematologic toxicity was significant but tolerable. High-dose 131I-MIBG may lead to long-term survival in patients with malignant pheochromocytoma.