Optimal hyperglycemia thresholds in patients undergoing chemotherapy: a cross sectional study of oncologists' practices.

PURPOSE: Neither the United States nor the European oncology guidelines include details for appropriate management of hyperglycemia in cancer patients. The aim was to identify fasting and random blood glucose thresholds, and hemoglobin A1c (HbA1c) targets used by oncologists in clinical practice when managing hyperglycemia in patients with cancer undergoing chemotherapy. METHODS: This national, cross sectional study utilized a questionnaire to collect oncologists' perceptions about optimal blood glucose thresholds and HbA1c targets in patients with cancer undergoing chemotherapy. Descriptive statistics were calculated to summarize glucose thresholds, HbA1c targets, and sample characteristics. Responses to an open-ended question about oncologists' approach to hyperglycemia management were analyzed via thematic analysis using an inductive approach. RESULTS: Respondents (n = 229) were on average 52.1 years of age, 67.7% men, and 91.3% White. For patients without diabetes but experiencing hyperglycemia, oncologists targeted lower and upper fasting blood glucose levels between 75-121 mg/dL and 105-135 mg/dL, respectively. For patients with diabetes, the targets for lower and upper fasting blood glucose levels ranged between 100-130 mg/dL and 128-150 mg/dL, respectively. Fasting blood glucose (95.6%) and HbA1c (78.6%) were the most commonly used clinical indicators to consider chemotherapy dose reduction, delay, or discontinuation due to hyperglycemia in patients receiving chemotherapy with curative intent. Among those receiving palliative intent chemotherapy, the preferred clinical parameters were random blood glucose (90.0%), patient-reported blood glucose readings (70.7%), continuous glucose monitoring readings (65.1%), and patient-reported symptoms of hyperglycemia (65.1%). Three main themes emerged about oncologists' approach to hyperglycemia management: 1) identification of high-risk patients; 2) need for early identification, screening, and diagnosis of hyperglycemia; and 3) multiple hyperglycemia management strategies. CONCLUSION: Oncologists reported a wide variation of target blood glucose ranges considered appropriate in patients undergoing chemotherapy. Lack of clear guidance for hyperglycemia management during chemotherapy in the United States may be contributing to a lack of consistency in clinical practice.

Gaps in Access to Medically Necessary Dental Care for Patients Living With and Beyond Cancer: We Must Do Better.

Delivery of high-quality, evidence-based oral care for those living with and beyond cancer needed!

Carious typodont teeth's effectiveness in pre-doctoral SIM lab to reinforce operative learning.

INTRODUCTION: The concept of ideal preparations in dental schools are highly emphasized during the first two years of students' learning. However, students do not have as much opportunity to practice skills that would prepare them for real-life stituations such as non-ideal preparations and caries removal. OBJECTIVE: This study aimed to determine the benefits of utilizing carious typodont teeth in the Operative curriculum for first- and second-year UCSF dental students METHODS: This study was completed by hosting a workshop in which the students performed a Class II preparation on #19 carious typodont tooth. The students filled out pre- and post-surveys with questions about their confidence with performing a preparation and their opinions on the current curriculum. RESULTS: The pre-survey responses showed that the majority of the first- and second-year students did not believe that the traditional non-carious typodont teeth were a good representation of prepping on real, carious teeth. The pre-survey responses also showed that most of the first- and second-year students thought that the addition of carious typodont teeth would improve their learning experience. The post-survey results displayed that the majority of the students thought that prepping carious typodont teeth helped to better reinforce concepts such as preparation design, taught them the difference between ideal and non-ideal preparations, and allowed them to better understand tooth anatomy with the addition of the dentin layer. CONCLUSION: The use of the carious typodont teeth in pre-clinical operative lab was found to be beneficial to first- and second-year UCSF student's learning based on the pre- and post-survey results.

Oncologists' responsibility, comfort, and knowledge managing hyperglycemia in patients with cancer undergoing chemotherapy: a cross sectional study.

PURPOSE: To assess oncologists' responsibility, comfort, and knowledge managing hyperglycemia in patients undergoing chemotherapy. METHODS: In this cross-sectional study, a questionnaire collected oncologists' perceptions about professionals responsible for managing hyperglycemia during chemotherapy; comfort (score range 12-120); and knowledge (score range 0-16). Descriptive statistics were calculated including Student t-tests and one-way ANOVA for mean score differences. Multivariable linear regression identified predictors of comfort and knowledge scores. RESULTS: Respondents (N = 229) were 67.7% men, 91.3% White and mean age 52.1 years. Oncologists perceived endocrinologists/diabetologists and primary care physicians as those responsible for managing hyperglycemia during chemotherapy, and most frequently referred to these clinicians. Reasons for referral included lack of time to manage hyperglycemia (62.4%), belief that patients would benefit from referral to an alternative provider clinician (54.1%), and not perceiving hyperglycemia management in their scope of practice (52.4%). The top-3 barriers to patient referral were long wait times for primary care (69.9%) and endocrinology (68.1%) visits, and patient's provider outside of the oncologist's institution (52.8%). The top-3 barriers to treating hyperglycemia were lack of knowledge about when to start insulin, how to adjust insulin, and what insulin type works best. Women (ß = 1.67, 95% CI: 0.16, 3.18) and oncologists in suburban areas (ß = 6.98, 95% CI: 2.53, 11.44) had higher comfort scores than their respective counterparts; oncologists working in practices with > 10 oncologists had lower comfort scores (ß = -2.75, 95% CI: -4.96, -0.53) than those in practices with ≤ 10. No significant predictors were identified for knowledge. CONCLUSION: Oncologists expected endocrinology or primary care clinicians to manage hyperglycemia during chemotherapy, but long wait times were among the top barriers cited when referring patients. New models that provide prompt and coordinated care are needed.

Salvage Cryoablation for Local Recurrences of Thyroid Cancer Inseparable from the Trachea and Neurovascular Structures.

PURPOSE: To demonstrate safety, feasibility, and effectiveness of cryoablation of recurrent papillary thyroid cancer ineligible for reoperation because of scarring, eligible for focal ablation as defined within 2015 American Thyroid Association guideline sections C16 and C17. MATERIALS AND METHODS: With multidisciplinary consensus, cryoablation was performed with curative intent for 15 tumors in 10 patients between January 2019 and July 2021. Demographics, procedural details, and serial postprocedural imaging findings were analyzed. RESULTS: The mean age was 72.5 years (range, 57-88 years), and 80% of the patients were women. The tumors (mean size, 16 mm ± 6; range, 9-29 mm) received 1 session of cryoablation with 100% technical success. The mean and median postcryoablation tumor volumetric involution rates were 88% and 99%, respectively, with 9 (60%) of 15 tumors involuting completely or down to the scar and 6 (40%) involuting partially at the end of the study period. Tumor size did not increase after cryoablation (0% local progression rate). All tumors abutted the trachea, skin, and/or vascular structures, and hydrodissection failed in all cases because of scarring. The major adverse event rate was 20% (3/15), with 2 cases of voice change and 1 case of Horner syndrome; all resolved at 6 months with no permanent sequelae. No vascular, tracheal, dermal, or infectious adverse events occurred during a mean follow-up of 242 days (range, 114-627 days). One patient died at 386 days after cryoablation because of unrelated cholangiocarcinoma. CONCLUSIONS: Cryoablation of local recurrences of papillary thyroid cancer abutting the trachea and/or neurovascular structures in the setting of hydrodissection failure because of scarring yielded a mean volumetric involution of 88%, primary efficacy of 60%, and objective response rate of 100% with no local recurrences or permanent complications during a mean follow-up of 242 days. The secondary efficacy and longer-term outcomes remain forthcoming.

Towards De-Implementation of low-value thyroid care in older adults.

PURPOSE OF REVIEW: This review discusses the current literature regarding low-value thyroid care in older adults, summarizing recent findings pertaining to screening for thyroid dysfunction and management of hypothyroidism, thyroid nodules and low-risk differentiated thyroid cancer. RECENT FINDINGS: Despite a shift to a "less is more" paradigm for clinical thyroid care in older adults in recent years, current studies demonstrate that low-value care practices are still prevalent. Ineffective and potentially harmful services, such as routine treatment of subclinical hypothyroidism which can lead to overtreatment with thyroid hormone, inappropriate use of thyroid ultrasound, blanket fine needle aspiration biopsies of thyroid nodules, and more aggressive approaches to low-risk differentiated thyroid cancers, have been shown to contribute to adverse effects, particularly in comorbid older adults. SUMMARY: Low-value thyroid care is common in older adults and can trigger a cascade of overdiagnosis and overtreatment leading to patient harm and increased healthcare costs, highlighting the urgent need for de-implementation efforts.

Artificial Intelligence-Guided Prediction of Dental Doses Before Planning of Radiation Therapy for Oropharyngeal Cancer: Technical Development and Initial Feasibility of Implementation.

Purpose: The aim was to develop a novel artificial intelligence (AI)-guided clinical decision support system, to predict radiation doses to subsites of the mandible using diagnostic computed tomography scans acquired before any planning of head and neck radiation therapy (RT). Methods and Materials: A dose classifier was trained using RT plans from 86 patients with oropharyngeal cancer; the test set consisted of an additional 20 plans. The classifier was trained to predict whether mandible subsites would receive a mean dose >50 Gy. The AI predictions were prospectively evaluated and compared with those of a specialist head and neck radiation oncologist for 9 patients. Positive predictive value (PPV), negative predictive value (NPV), Pearson correlation coefficient, and Lin concordance correlation coefficient were calculated to compare the AI predictions to those of the physician. Results: In the test data set, the AI predictions had a PPV of 0.95 and NPV of 0.88. For 9 patients evaluated prospectively, there was a strong correlation between the predictions of the AI algorithm and physician (P = .72, P < .001). Comparing the AI algorithm versus the physician, the PPVs were 0.82 versus 0.25, and the NPVs were 0.94 versus 1.0, respectively. Concordance between physician estimates and final planned doses was 0.62; this was 0.71 between AI-based estimates and final planned doses. Conclusion: AI-guided decision support increased precision and accuracy of pre-RT dental dose estimates.

Probable Delirium as a Risk Factor for Adverse Surgical Outcomes in Geriatric Patients With Acute Hip Fracture: Preoperative Assessment Using a Short Screening Tool.

Hip fractures in geriatric patients are associated with substantial morbidity and mortality including postoperative delirium. Few data are available regarding preoperative identification of patients at risk of postoperative delirium before surgical repair of hip fracture. We used the Ultrabrief Two-Item Bedside Test, a proxy for delirium, to identify patients who are likely to have adverse outcomes postoperatively. This prospective pilot study included patients 65 years and older with an acute hip fracture. The questionnaire was administered preoperatively, and patients were followed up for 30 days postoperatively. We enrolled 30 patients, with a mean age of 78 years. The 12 patients with an abnormal test result had a significantly lower body mass index, a trend in descriptive statistics for pulmonary disease, and a higher ASA physical status. In addition, hospital stay following fracture repair was longer for patients with an abnormal test result, although not significantly (mean [SD]=8.8 [4.2] days vs 6.4 [2.0] days, median=8 vs 6 days, log-rank P=.052). A 2-item questionnaire could help identify patients who have sustained hip fracture who are likely to have a longer hospitalization. Future studies are needed to confirm these findings and determine whether interventions can reduce risk.

Postoperative Surveillance in Older Adults With T1N0M0 Low-risk Papillary Thyroid Cancer.

BACKGROUND: The frequency and cost of postoperative surveillance for older adults (>65 y) with T1N0M0 low-risk papillary thyroid cancer (PTC) have not been well studied. METHODS: Using the SEER-Medicare (2006-2013) database, frequency and cost of surveillance concordant with American Thyroid Association (ATA) guidelines (defined as an office visit, ≥1 thyroglobulin measurement, and ultrasound 6- to 24-month postoperatively) were analyzed for the overall cohort of single-surgery T1N0M0 low-risk PTC, stratified by lobectomy versus total thyroidectomy. RESULTS: Majority of 2097 patients in the study were white (86.7%) and female (77.5%). Median age and tumor size were 72 y (interquartile range 68-76) and 0.6 cm (interquartile range 0.3-1.1 cm), respectively; 72.9% of patients underwent total thyroidectomy. Approximately 77.5% of patients had a postoperative surveillance visit; however, only 15.9% of patients received ATA-concordant surveillance. Patients who underwent total thyroidectomy as compared with lobectomy were more likely to undergo surveillance testing, thyroglobulin (61.7% versus 24.8%) and ultrasound (37.5% versus 29.2%) (all P < 0.01), and receive ATA-concordant surveillance (18.5% versus 9.0%, P < 0.001). Total surveillance cost during the study period was $621,099. Diagnostic radioactive iodine, ablation, and advanced imaging (such as positron emission tomography scans) accounted for 55.5% of costs ($344,692), whereas ATA-concordant care accounted for 44.5% of costs. After multivariate adjustment, patients who underwent total thyroidectomy as compared with lobectomy were twice as likely to receive ATA-concordant surveillance (adjusted odds ratio 2.0, 95% confidence interval: 1.5-2.8, P < 0.001). CONCLUSIONS: Majority of older adults with T1N0M0 low-risk PTC do not receive ATA-concordant surveillance; discordant care was costly. Total thyroidectomy was the strongest predictor of receiving ATA-concordant care.

The Use of Alfaxalone in Quaker Parrots (Myiopsitta monachus).

Alfaxalone is a neurosteroid anesthetic that acts on gamma-aminobutyric acid alpha-receptors. The objective of this study was to evaluate the clinical safety and efficacy of alfaxalone (Alfaxan CD). Due to observed hyperexcitability in the subject animals when alfaxalone was the only drug used during the initial trials, premedication with midazolam was also evaluated during the final study. Ten adult Quaker parrots (Myiopsitta monachus) were assigned to 3 groups: 1) low-dose alfaxalone 10 mg/kg (LD), 2) high-dose alfaxalone 25 mg/kg (HD), and 3) alfaxalone 10 mg/ kg with midazolam 1 mg/kg premedication (AM), administered intramuscularly. Induction time, sedation quality, duration of action, and vital parameters, including heart rate, respiratory rate, and temperature, were recorded. All protocols achieved adequate sedation; however, muscle tremors and hyperexcitation were variable. The LD group had a significantly longer mean ± SD induction time (13.5 ± 4.5 minutes) as compared to the HD (6.0 ± 1.3 minutes, P = .002) and AM (6.5 ± 2.9 minutes, P = .006) groups, while recovery time was significantly longer in the HD group (86.2 ± 13.4 minutes) than the LD group (44.4 ± 10.8 minutes, P < .001). Midazolam premedication resulted in reduction of both muscle tremors and hyperexcitation associated with alfaxalone administration, but the recovery time was significantly longer (103.5 ± 15.1 minutes, P < .001) than for the LD group. Alfaxalone as a sole agent resulted in muscle tremors and hyperexcitation during induction, which was attenuated by premedication with midazolam. Further investigation is warranted to characterize the effects of alfaxalone and drugs used to premedicate Quaker parrots.

A DIRECT COMPARISON OF THE ATA AND TI-RADS ULTRASOUND SCORING SYSTEMS.

Objective: This study compares the American Thyroid Association (ATA) classification system with the 2017 American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) for predicting cancer risk in thyroid nodules. Methods: This is a retrospective review of ultrasound imaging of all adult patients with thyroid nodules >5 mm who underwent thyroidectomy at a tertiary care hospital in 2016. We assessed the ability of either system to predict malignancy based on surgical histopathology. Sensitivity, specificity, negative predictive values (NPV) and positive predictive values (PPV), and area-under-the-curve (AUC) were calculated and compared using McNemar's, Fisher exact, or DeLong's tests. Results: Three hundred and twenty-three nodules from 213 adults were included. Median patient age was 55 years; 75.6% were female. 27.2% nodules were malignant. Both ATA and ACR TI-RADS provide effective diagnostic performance, a sensitivity of 77.3% versus 78.4%, respectively, a specificity of 76.6% versus 73.2%, respectively, a PPV of 55.3% versus 52.3%, respectively, and a NPV of 90% for both. The level of agreement between the two classification systems was almost perfect (weighted Kappa statistic = 0.93, AUC 0.77 ATA versus 0.76 TI-RADS [P = .18]). However, of the 40 (TI-RADS level 3) TR3 nodules (<2.5 cm), 10% were malignant, and of the 31 (TI-RADS level 4) TR4 nodules (<1.5 cm), 38% were malignant. Conclusion: The ATA and TI-RADS classification systems appear to have similar diagnostic value for predicting thyroid cancer. However, subanalysis of TR3 and TR4 nodules with consideration of size criteria showed that there is a higher risk of missing a malignancy if the ACR TI-RADS recommendation is followed. These results should be validated in a different patient cohort with a lower incidence of cancer. Abbreviations: ACR = American College of Radiology; ATA = American Thyroid Association; FNA = Fine Needle Aspiration; κ = weighted Kappa statistic; NPV = negative predictive values; PPV = positive predictive values; TI-RADS = Thyroid Imaging Reporting and Data System; TR1 = TI-RADS level 1; TR2 = TI-RADS level 2; TR3 = TI-RADS level 3; TR4 = TI-RADS level 4; TR5 = TI-RADS level 5.

Best Practices in Transgender Health: A Clinician's Guide.

Providing culturally competent and medically knowledgeable care to the transgender community is increasingly falling within the realms of practice for primary care providers. The purpose of this article is to provide an overview of best practices as they relate to transgender care. This article is by no means a comprehensive guide, but rather a starting point for clinicians as they provide high-quality care to their transgender patients.

Arachnoid diverticulum diagnosis following treatment of cryptococcal meningitis in a dog.

Successful long-term treatment of cryptococcal meningitis in dogs is clinically challenging. In humans, there are only rare case reports of complications post-treatment including arachnoid diverticula. Combination antifungal therapy is standard of practice in human medicine and should be considered in veterinary patients.

Lobectomy for treatment of differentiated thyroid cancer: can patients avoid postoperative thyroid hormone supplementation and be compliant with the American Thyroid Association guidelines?

BACKGROUND: The American Thyroid Association recommended thyroid lobectomy as an alternative for low-risk differentiated thyroid cancer. One hypothetical benefit includes avoiding lifelong thyroid hormone supplementation; however, guidelines recommend maintaining the thyroid-stimulating hormone <2 mIU/L postoperatively in low-risk patients. Our hypothesis is that most patients will require hormone supplementation to maintain thyroid-stimulating hormone <2 mIU/L, minimizing this advantage of lobectomy. The goal of this study is to determine how often patients have thyroid-stimulating hormone <2 mIU/L after lobectomy without thyroid hormone supplementation. METHODS: A retrospective review of 555 consecutive patients who underwent thyroid lobectomy was performed. Thyroid hormone supplementation was documented, along with thyroid-stimulating hormone levels preoperatively, 7 to 10 days, and 2 to 12 months postoperatively. RESULTS: In the study, 478/555 (86%) patients did not take thyroid hormone before thyroidectomy; 394/478 (82%) had thyroid-stimulating hormone levels available at 7 to 10 days postoperatively, and of these, 218 (55%) had thyroid-stimulating hormone >2 mIU/L. From 2 to 12 months postoperatively, of the 225 patients who continued to remain off thyroid hormone supplementation, 132 (59%) experienced a thyroid-stimulating hormone increase to >2 mIU/L; therefore, 350/478 (73%) patients after thyroid lobectomy had thyroid-stimulating hormone levels >2 mIU/L within a year. CONCLUSION: It is important to counsel patients that to be compliant with the American Thyroid Association guidelines for differentiated thyroid cancer, the majority of patients undergoing thyroid lobectomy may require thyroid hormone supplementation to maintain a thyroid-stimulating hormone level <2 m IU/L.

A practical method of I-131 thyroid cancer therapy dose optimization using estimated effective renal clearance.

In thyroid cancer patients with renal impairment or other complicating factors, it is important to maximize I-131 therapy efficacy while minimizing bone marrow and lung damage. We developed a web-based calculator based on a modified Benua and Leeper method to calculate the maximum I-131 dose to reduce the risk of these toxicities, based on the effective renal clearance of I-123 as measured from two whole-body I-123 scans, performed at 0 and 24 h post-administration.

The Impact of Pathologically Positive Lymph Nodes in the Clinically Negative Neck: An Analysis of 39,301 Patients with Papillary Thyroid Cancer.

PURPOSE: Management of patients with low-risk papillary thyroid cancer (PTC) with clinically uninvolved lymph nodes (cN0 LNs), but who harbor metastatic central LNs (pN1a), remains unclear. The number of central LNs examined, radioactive iodine (RAI) utilization, and survival were compared across cN0 patients based on pN stage: pN0 (negative) versus pNx (unknown) versus pN1a (pathologically positive). METHODS: Adults with a PTC ≥1 cm who were cN0 preoperatively were compared based on surgical pathology using the National Cancer Data Base (NCDB; 2003-2011), after univariate and multivariate adjustment. Overall survival (OS) was examined using Kaplan-Meier curves, the log-rank test, and Cox proportional hazards modeling. RESULTS: Overall, 39,301 patients were included; median tumor size was 1.9 cm. More LNs were examined for pN1a versus pN0 diagnosis (pN1a median = 5 LNs vs. pN0 median = 2 LNs; p < 0.0001), with a median of two central LNs found to be positive on surgical resection. Compared with pN0, pN1a patients were 78% more likely to receive RAI (odds ratio 1.78, 95% confidence interval [CI] 1.65-1.91; p < 0.0001). After adjusting for receipt of RAI, no difference in OS was observed for pN1a versus pN0 or pNx patients (p = 0.72). Treatment with RAI was associated with improved OS (hazard ratio 0.78, 95% CI 0.62-0.98, p = 0.03), but the effect of RAI did not differ based on pN stage (interaction p = 0.67). CONCLUSION: More LNs were examined for positive versus negative pN diagnosis in patients with cN0 PTC. Unsuspected central neck nodal metastases in cN0 PTC patients are associated with increased RAI utilization, but no survival difference.

Comparative effects of acute hypoglycemia and hyperglycemia on pro-atherothrombotic biomarkers and endothelial function in non-diabetic humans.

BACKGROUND: The comparative effects of acute moderate hyperglycemia and hypoglycemia on in vivo endothelial function together with pro-inflammatory and pro-atherothrombotic responses in healthy individuals have not been determined. METHODS: To investigate this question, 45 healthy subjects were compared during glucose clamp studies consisting of euinsulinemic hyperglycemia and hyperinsulinemic hyperglycemia (plasma glucose 11.1mmol/L, both with pancreatic clamps) and hyperinsulinemic euglycemia and hyperinsulinemic hypoglycemia (plasma glucose 5.1 and 2.9mmol/L, respectively). Two-dimensional Doppler ultrasound was used to determine brachial artery endothelial function. RESULTS: Insulin levels during euinsulinemia hyperglycemia were 194±23 and (850±49-988±114) pmol/L during all hyperinsulinemic protocols. Responses of VCAM-1, ICAM-1, E-selectin, P-selectin, PAI-1, and IL-6 were increased (p<0.05-0.0001) during euinsulinemic hyperglycemia or hypoglycemia as compared to hyperinsulinemic euglycemia or hyperinsulinemic hyperglycemia. PAI-1 was increased (p<0.04) during hypoglycemia as compared to euinsulinemic hyperglycemia, and TNF-α responses were also increased during hypoglycemia as compared to hyperinsulinemic euglycemia or hyperinsulinemic hyperglycemia (p<0.05). In vivo endothelial function was similarly blunted by acute moderate hyperglycemia or hypoglycemia. CONCLUSION: In summary, acute moderate hypoglycemia and euinsulinemic hyperglycemia can result in similar endothelial dysfunction and pro-atherothrombotic responses. Fibrinolytic balance was reduced by a greater extent by hypoglycemia as compared to moderate hyperglycemia. Acutely, hyperinsulinemia can prevent the acute pro-atherothrombotic and pro-inflammatory effects of moderate hyperglycemia but not hypoglycemia.

Modular elements of the TPR domain in the Mps1 N terminus differentially target Mps1 to the centrosome and kinetochore.

Faithful segregation of chromosomes to two daughter cells is regulated by the formation of a bipolar mitotic spindle and the spindle assembly checkpoint, ensuring proper spindle function. Here we show that the proper localization of the kinase Mps1 (monopolar spindle 1) is critical to both these processes. Separate elements in the Mps1 N-terminal extension (NTE) and tetratricopeptide repeat (TPR) domains govern localization to either the kinetochore or the centrosome. The third TPR (TPR3) and the TPR-capping helix (C-helix) are each sufficient to target Mps1 to the centrosome. TPR3 binds to voltage-dependent anion channel 3, but although this is sufficient for centrosome targeting of Mps1, it is not necessary because of the presence of the C-helix. A version of Mps1 lacking both elements cannot localize to or function at the centrosome, but maintains kinetochore localization and spindle assembly checkpoint function, indicating that TPR3 and the C-helix define a bipartite localization determinant that is both necessary and sufficient to target Mps1 to the centrosome but dispensable for kinetochore targeting. In contrast, elements required for kinetochore targeting (the NTE and first two TPRs) are dispensable for centrosomal localization and function. These data are consistent with a separation of Mps1 function based on localization determinants within the N terminus.

Comparison of Outcomes: Nurse-Driven vs. Physician-Driven Weight-Based Intravenous Heparin Protocol.

The transition from a physician-driven heparin protocol to a nurse- driven heparin protocol at one institution resulted in shorter times to therapeutic activated partial thromboplastin time (aPTT), increased time within goal aPTT range, and an increased percent- age of patients who ultimately achieved a therapeutic aPTT.