A validated preoperative risk prediction tool for extended inpatient length of stay following anatomic or reverse total shoulder arthroplasty.

BACKGROUND: Recent work has shown inpatient length of stay (LOS) following shoulder arthroplasty to hold the second strongest association with overall cost (after implant cost itself). In particular, a preoperative understanding for the patients at risk of extended inpatient stays (≥3 days) can allow for counseling, optimization, and anticipating postoperative adverse events. METHODS: A multicenter retrospective review was performed of 5410 anatomic (52%) and reverse (48%) total shoulder arthroplasties done at 2 large, tertiary referral health systems. The primary outcome was extended inpatient LOS of at least 3 days, and over 40 preoperative sociodemographic and comorbidity factors were tested for their predictive ability in a multivariable logistic regression model based on the patient cohort from institution 1 (derivation, N = 1773). External validation was performed using the patient cohort from institution 2 (validation, N = 3637), including area under the receiver operator characteristic curve (AUC), sensitivity, specificity, and positive and negative predictive values. RESULTS: A total of 814 patients, including 318 patients (18%) in the derivation cohort and 496 patients (14%) in the validation cohort, experienced an extended inpatient LOS of at least 3 days. Four hundred forty-five (55%) were discharged to a skilled nursing or rehabilitation facility. Following parameter selection, a multivariable logistic regression model based on the derivation cohort (institution 1) demonstrated excellent preliminary accuracy (AUC: 0.826), with minimal decrease in accuracy under external validation when tested against the patients from institution 2 (AUC: 0.816). The predictive model was composed of only preoperative factors, in descending predictive importance as follows: age, marital status, fracture case, ASA (American Society of Anesthesiologists) score, paralysis, electrolyte disorder, body mass index, gender, neurologic disease, coagulation deficiency, diabetes, chronic pulmonary disease, peripheral vascular disease, alcohol dependence, psychoses, smoking status, and revision case. CONCLUSION: A freely-available, preoperative online clinical decision tool for extended inpatient LOS (≥ 3 days) after shoulder arthroplasty reaches excellent predictive accuracy under external validation. As a result, this tool merits consideration for clinical implementation, as many risk factors are potentially modifiable as part of a preoperative optimization strategy.

Assessment of conditions leading to lost-to-follow-up of head and neck cancer patients.

PURPOSE: Head and neck cancer patients require close clinical follow up to monitor and address sequelae of treatment and for adequate cancer surveillance. The goal of this study is to determine barriers and risk factors for head and neck cancer patients who are lost-to-follow-up. MATERIALS AND METHODS: A chart review of the Head and Neck Cancer Registry was performed to identify patients who were lost-to-follow-up (LTF). LTF was defined as missing two consecutive appointments as recommended by their oncologic surgeon. Those identified as LTF were contacted via email and phone to complete a 16-question survey addressing possible barriers to follow up. RESULTS: Of the 353 patients reviewed, 53 met the criteria for LTF (15%). Forty-eight participants were contacted, and 23 surveys were completed (48%). Of the 23 patients that responded, 22% reported difficulty scheduling an appointment, 30% had transportation barriers, 22% had personal or work obligations that prevented follow up, 17% did not follow up because they "felt better," and 39% were following up with an otolaryngologist or oncologist closer to home. Only three participants (13%) were aware of the recommended 5-year surveillance period. CONCLUSION: Head and neck cancer patients have a variety of reasons they are lost to follow-up. Understanding these barriers is critical to creating a patient-centered model that balances both clinical surveillance needs and reasonable expectations for patients. Improvements can be made to educate patients on the recommended length of follow-up and its importance.

Appropriate patient selection for outpatient shoulder arthroplasty: a risk prediction tool.

BACKGROUND: The transition from inpatient to outpatient shoulder arthroplasty critically depends on appropriate patient selection, both to ensure safety and to counsel patients preoperatively regarding individualized risk. Cost and patient demand for same-day discharge have encouraged this transition, and a validated predictive tool may help decrease surgeon liability for complications and help select patients appropriate for same-day discharge. We hypothesized that an accurate predictive model could be created for short inpatient length of stay (discharge at least by postoperative day 1), potentially serving as a useful proxy for identifying patients appropriate for true outpatient shoulder arthroplasty. METHODS: A multicenter cohort of 5410 shoulder arthroplasties (2805 anatomic and 2605 reverse shoulder arthroplasties) from 2 geographically diverse, high-volume health systems was reviewed. Short inpatient stay was the primary outcome, defined as discharge on either postoperative day 0 or 1, and 49 patient outcomes and factors including the Elixhauser Comorbidity Index, sociodemographic factors, and intraoperative parameters were examined as candidate predictors for a short stay. Factors surviving parameter selection were incorporated into a multivariable logistic regression model, which underwent internal validation using 10,000 bootstrapped samples. RESULTS: In total, 2238 patients (41.4%) were discharged at least by postoperative day 1, with no difference in rates of 90-day readmission (3.5% vs. 3.3%, P = .774) between cohorts with a short length of stay and an extended length of stay (discharge after postoperative day 1). A multivariable logistic regression model demonstrated high accuracy (area under the receiver operator characteristic curve, 0.762) for discharge by postoperative day 1 and was composed of 13 variables: surgery duration, age, sex, electrolyte disorder, marital status, American Society of Anesthesiologists score, paralysis, diabetes, neurologic disease, peripheral vascular disease, pulmonary circulation disease, cardiac arrhythmia, and coagulation deficiency. The percentage cutoff maximizing sensitivity and specificity was calculated to be 47%. Internal validation showed minimal loss of accuracy after bias correction for overfitting, and the predictive model was incorporated into a freely available online tool to facilitate easy clinical use. CONCLUSIONS: A risk prediction tool for short inpatient length of stay after shoulder arthroplasty reaches very good accuracy despite requiring only 13 variables and was derived from an underlying database with broad geographic diversity in the largest institutional shoulder arthroplasty cohort published to date. Short inpatient length of stay may serve as a proxy for identifying patients appropriate for same-day discharge, although perioperative care decisions should always be made on an individualized and holistic basis.

A validated preoperative risk prediction tool for discharge to skilled nursing or rehabilitation facility following anatomic or reverse shoulder arthroplasty.

BACKGROUND: As bundled payment models continue to spread, understanding the primary drivers of cost excess helps providers avoid penalties and ensure equal health care access. Recent work has shown discharge to rehabilitation and skilled nursing facilities (SNFs) to be a primary cost driver in total joint arthroplasty, and an accurate preoperative risk calculator for shoulder arthroplasty would not only help counsel patients in clinic during shared decision-making conversations but also identify high-risk individuals who may benefit from preoperative optimization and discharge planning. METHODS: Anatomic and reverse total shoulder arthroplasty cohorts from 2 geographically diverse, high-volume centers were reviewed, including 1773 cases from institution 1 (56% anatomic) and 3637 from institution 2 (50% anatomic). The predictive ability of a variety of candidate variables for discharge to SNF/rehabilitation was tested, including case type, sociodemographic factors, and the 30 Elixhauser comorbidities. Variables surviving parameter selection were incorporated into a multivariable logistic regression model built from institution 1's cohort, with accuracy then validated using institution 2's cohort. RESULTS: A total of 485 (9%) shoulder arthroplasties overall were discharged to post-acute care (anatomic: 6%, reverse: 14%, P < .0001), and these patients had significantly higher rates of unplanned 90-day readmission (5% vs. 3%, P = .0492). Cases performed for preoperative fracture were more likely to require post-acute care (13% vs. 3%, P < .0001), whereas revision cases were not (10% vs. 10%, P = .8015). A multivariable logistic regression model derived from the institution 1 cohort demonstrated excellent preliminary accuracy (area under the receiver operating characteristic curve [AUC]: 0.87), requiring only 11 preoperative variables (in order of importance): age, marital status, fracture, neurologic disease, paralysis, American Society of Anesthesiologists physical status, gender, electrolyte disorder, chronic pulmonary disease, diabetes, and coagulation deficiency. This model performed exceptionally well during external validation using the institution 2 cohort (AUC: 0.84), and to facilitate convenient use was incorporated into a freely available, online prediction tool. A model built using the combined cohort demonstrated even higher accuracy (AUC: 0.89). CONCLUSIONS: This validated preoperative clinical decision tool reaches excellent predictive accuracy for discharge to SNF/rehabilitation following shoulder arthroplasty, providing a vital tool for both patient counseling and preoperative discharge planning. Further, model parameters should form the basis for reimbursement legislation adjusting for patient comorbidities, ensuring no disparities in access arise for at-risk populations.

Circulating tumor DNA guided adjuvant chemotherapy in stage II colon cancer (MEDOCC-CrEATE): study protocol for a trial within a cohort study.

BACKGROUND: Accurate detection of patients with minimal residual disease (MRD) after surgery for stage II colon cancer (CC) remains an urgent unmet clinical need to improve selection of patients who might benefit form adjuvant chemotherapy (ACT). Presence of circulating tumor DNA (ctDNA) is indicative for MRD and has high predictive value for recurrent disease. The MEDOCC-CrEATE trial investigates how many stage II CC patients with detectable ctDNA after surgery will accept ACT and whether ACT reduces the risk of recurrence in these patients. METHODS/DESIGN: MEDOCC-CrEATE follows the 'trial within cohorts' (TwiCs) design. Patients with colorectal cancer (CRC) are included in the Prospective Dutch ColoRectal Cancer cohort (PLCRC) and give informed consent for collection of clinical data, tissue and blood samples, and consent for future randomization. MEDOCC-CrEATE is a subcohort within PLCRC consisting of 1320 stage II CC patients without indication for ACT according to current guidelines, who are randomized 1:1 into an experimental and a control arm. In the experimental arm, post-surgery blood samples and tissue are analyzed for tissue-informed detection of plasma ctDNA, using the PGDx elio™ platform. Patients with detectable ctDNA will be offered ACT consisting of 8 cycles of capecitabine plus oxaliplatin while patients without detectable ctDNA and patients in the control group will standard follow-up according to guideline. The primary endpoint is the proportion of patients receiving ACT when ctDNA is detectable after resection. The main secondary outcome is 2-year recurrence rate (RR), but also includes 5-year RR, disease free survival, overall survival, time to recurrence, quality of life and cost-effectiveness. Data will be analyzed by intention to treat. DISCUSSION: The MEDOCC-CrEATE trial will provide insight into the willingness of stage II CC patients to be treated with ACT guided by ctDNA biomarker testing and whether ACT will prevent recurrences in a high-risk population. Use of the TwiCs design provides the opportunity to randomize patients before ctDNA measurement, avoiding ethical dilemmas of ctDNA status disclosure in the control group. TRIAL REGISTRATION: Netherlands Trial Register: NL6281/NTR6455 . Registered 18 May 2017, https://www.trialregister.nl/trial/6281.

Correction to: Neurological Symptoms in Hypophosphatasia.

Due to a typesetting error the title of the article was published wrongly.

Neurological symptoms in Hypophosphatasia.

Hypophosphatasia (HPP) typically manifests with fractures, tooth loss, and muscle pain. Although mental health diagnoses and neurological symptoms have not been previously well documented in HPP, they occur commonly. The recognition of non-traditional symptoms may improve patient satisfaction, preempt costly evaluation and misdiagnosis, and lead to further treatment options. INTRODUCTION: Hypophosphatasia (HPP) is an inborn error of metabolism due to deficiency of tissue non-specific alkaline phosphatase (TNSALP). It is traditionally characterized by rickets in children and osteomalacia in adults, along with fractures, tooth loss, and muscle pain. Neurological symptoms and mental health diagnoses have not been widely reported, and we therefore report their prevalence in a cohort of patients with HPP. METHODS: A retrospective chart review was performed on a series of 82 HPP patients. Patient charts were reviewed to identify the possible presence and onset of 13 common neurological symptoms. RESULTS: Median age was 36 years (2 to 79). Seventeen had adult onset HPP (> 18 years) and 65 had pediatric onset HPP (< 18 years). Median time from symptom onset to HPP diagnosis was 8 years (0 to 67). Seventy-four percent had a family history of bone disease, while 17% had a family history of neurologic disease. Bone problems occurred in 89%, dental problems in 77%, and muscle problems in 66%. Fatigue occurred in 66%, headache in 61%, sleep disturbance in 51%, gait change in 44%, vertigo in 43%, depression in 39%, anxiety in 35%, neuropathy in 35%, and hearing loss in 33%. CONCLUSIONS: The extra-skeletal manifestations of HPP, specifically neurological symptoms, have not been previously well documented. However, mental health diagnoses and neurological symptoms such as headache and sleep disturbance occur commonly in patients with HPP. The recognition of non-traditional symptoms in HPP may improve patient satisfaction, preempt costly evaluation and misdiagnosis, and may lead to further treatment options.

Dynamic gut microbiome changes following regional intestinal lymphatic obstruction in primates.

The pathogenesis of inflammatory bowel disease (IBD) has been linked with lymphostasis, but whether and how lymphatic obstruction might disturb the intestinal microbiome in the setting of Crohn's Disease (CD) is currently unknown. We employed a new model of CD in African Green monkeys, termed 'ATLAS' (African green monkey truncation of lymphatics with obstruction and sclerosis), to evaluate how gut lymphatic obstruction alters the intestinal microbiome at 7, 21 and 61 days. Remarkable changes in several microbial sub- groupings within the gut microbiome were observed at 7 days post-ATLAS compared to controls including increased abundance of Prevotellaceae and Bacteroidetes-Prevotella-Porphyromonas (BPP), which may contribute to disease activity in this model of gut injury. To the best of our knowledge, these findings represent the first report linking lymphatic structural/gut functional changes with alterations in the gut microbiome as they may relate to the pathophysiology of CD.

Direct visualization of particle attachment to a pendant drop.

An experimental investigation is carried out into the attachment of a single particle to a liquid drop. High-speed videography is used to directly visualize the so-called 'snap-in' effect which occurs rapidly over sub-millisecond timescales. Using high-magnification, the evolution of the contact line around the particle is tracked and dynamic features such as the contact angle, wetted radius and force are extracted from these images to help build a fundamental understanding of the process. By examining the wetted length in terms of an arc angle, ϕ, it is shown that the early wetting stage is an inertial-dominated process and best described by a power law relation, i.e. ϕ ∼ (t/τ)α, where τ is an inertial timescale. For the subsequent lift-off stage, the initial particle displacement is matched with that predicted using a simple balance between particle weight and capillary force with reasonable agreement. The lift-off force is shown to be on the order of 1-100 µN, whilst the force of impacting droplets is known to be on the order of 10-1000 mN. This explains the ease in which liquid marbles are formed during impact experiments.

Progressive structural modification to a zinc-actuated photoinduced electron transfer (PeT) switch in the context of intracellular zinc imaging.

Photoinduced electron transfer (PeT)-type fluorescent molecular switches are often applied in ion-selective sensors. Zinc-targeting sensors that contain an anilino-based electron donor (aka, the PeT 'switch') have multiple advantages over those with an aliphatic amino switch. In addition to the lower pKa value of an aniline than that of a comparably substituted aliphatic amine, which reduces the interference of pH on the spectral properties of the attached fluorophore, the oxidation potentials of anilino groups are lower than those of aliphatic amino counterparts, which make them better electron donors in PeT. The effectiveness of anilino as a PeT switch is evaluated in a series of zinc-sensitive sensors that contain different fluorophores, zinc-binding ligands, and alkyl linkers between ligand and fluorophore. The abilities of these compounds to distinguish high and low intracellular zinc concentrations in living cells are demonstrated.

Feline Mammary Cancer.

Feline mammary carcinoma (FMC) is similar to human breast cancer in the late age of onset, incidence, histopathologic features, biological behavior, and pattern of metastasis. Therefore, FMC has been proposed as a relevant model for aggressive human breast cancer. The goals of this study were to develop a nude mouse model of FMC tumor growth and metastasis and to measure the expression of genes responsible for lymphangiogenesis, angiogenesis, tumor progression, and lymph node metastasis in FMC tissues and cell lines. Two primary FMC tissues were injected subcutaneously, and 6 FMC cell lines were injected into 3 sites (subcutaneous, intratibial, and intracardiac) in nude mice. Tumors and metastases were monitored using bioluminescent imaging and characterized by gross necropsy, radiology, and histopathology. Molecular characterization of invasion and metastasis genes in FMC was conducted using quantitative real-time reverse transcription polymerase chain reaction in 6 primary FMC tissues, 2 subcutaneous FMC xenografts, and 6 FMC cell lines. The histologic appearance of the subcutaneous xenografts resembled the primary tumors. No metastasis was evident following subcutaneous injection of tumor tissues and cell lines, whereas lung, brain, liver, kidney, eye, and bone metastases were confirmed following intratibial and intracardiac injection of FMC cell lines. Finally, 15 genes were differentially expressed in the FMC tissues and cell lines. The highly expressed genes in all samples were PDGFA, PDGFB, PDGFC, FGF2, EGFR, ERBB2, ERBB3, VEGFD, VEGFR3, and MYOF. Three genes ( PDGFD, ANGPT2, and VEGFC) were confirmed to be of stromal origin. This investigation demonstrated the usefulness of nude mouse models of experimental FMC and identified molecular targets of FMC progression and metastasis.

Study protocol: families and childhood transitions study (FACTS) - a longitudinal investigation of the role of the family environment in brain development and risk for mental health disorders in community based children.

BACKGROUND: Extant research has demonstrated that parenting behaviour can be a significant contributor to the development of brain structure and mental health during adolescence. Nonetheless, there is limited research examining these relationships during late childhood, and particularly in the critical period of brain development occurring between 8 and 10 years of age. The effects of the family environment on the brain during late childhood may have significant implications for later functioning, and particularly mental health. The Families and Childhood Transitions Study (FACTS) is a multidisciplinary longitudinal cohort study of brain development and mental health, with two waves of data collection currently funded, occurring 18-months apart, when child participants are aged approximately 8- and 10-years old. METHODS/DESIGN: Participants are 163 children (M age [SD] = 8.44 [0.34] years, 76 males) and their mothers (M age [SD] = 40.34 [5.43] years). Of the 163 families who consented to participate, 156 completed a video-recorded and observer-coded dyadic interaction task and 153 completed a child magnetic resonance imaging brain scan at baseline. Families were recruited from lower socioeconomic status (SES) areas to maximise rates of social disadvantage and variation in parenting behaviours. All experimental measures and tasks completed at baseline are repeated at an 18-month follow-up, excluding the observer coded family interaction tasks. The baseline assessment was completed in October 2015, and the 18-month follow up will be completed May 2017. DISCUSSION: This study, by examining the neurobiological and mental health consequences of variations in parenting, has the potential to significantly advance our understanding of child development and risk processes. Recruitment of lower SES families will also allow assessment of resilience factors given the poorer outcomes often associated with this population.

Noise interference with echo delay discrimination in bat biosonar.

Echolocating big brown bats (Eptesicus fuscus) were trained in a two-choice task to discriminate differences in the delay of electronic echoes at 1.7 ms delay (30 cm simulated range). Difference thresholds (∼45 µs) were comparable to previously published results. At selected above-threshold differences (116 and 232 µs delay), performance was measured in the presence of wideband random noise at increasing amplitudes in 10-dB steps to determine the noise level that prevented discrimination. Performance eventually failed, but the bats increased the amplitude and duration of their broadcasts to compensate for increasing noise, which allowed performance to persist at noise levels about 25 dB higher than without compensation. In the 232-µs delay discrimination condition, echo signal-to-noise ratio (2E/N0) was 8-10 dB at the noise level that depressed performance to chance. Predicted echo-delay accuracy using big brown bat signals follows the Cramér-Rao bound for signal-to-noise ratios above 15 dB, but worsens below 15 dB due to side-peak ambiguity. At 2E/N0 = 7-10 dB, predicted Cramér-Rao delay accuracy would be about 1 µs; considering side-peak ambiguity it would be about 200-300 µs. The bats' 232 µs performance reflects the intrusion of side-peak ambiguity into delay accuracy at low signal-to-noise ratios.

A Case of Early Neurosyphilis.

INTRODUCTION: Neurosyphilis is an infection of the central nervous system by Treponema pallidum, which can occur after the initial syphilis infection. Although commonly associated with late stage disease, patients with early neurosyphilis may present with acute syphilitic meningitis, meningovascular syphilis, or uveitis. CASE: A 28 year old man with a past medical history of HIV (CD4 364);, and recent diagnosis of uveitis presented to the Emergency Department with a positive RPR result. His visual acuity had been gradually declining over the past few months. He denied painless or painful ulcerating lesions on his penis, or scrotum, difficulty concentrating, dermatitis on the soles/palms, or difficulty with proprioception. Physical exam was notable for atrophic hyperpigmented polycyclic, annular plaques and patches along the hairline as well as several areas of confluent hyperpigmented polycyclic plaques and nodules on the patient's face, back, left arm, and right posterior leg. Fundoscopic exam revealed bilateral posterior uveitis and chorioretinitis. Evaluation of cerebrospinal fluid revealed a lymphocytic pleocytosis with a positive VDRL and FTA-ABS. Aqueous crystalline penicillin G was initiated for treatment of early neurosyphilis. Within six hours of beginning the infusion, the patient had a documented temperature of 101.8°F, heart rate of 128 beats per minute, blood pressure 142/84, with generalized malaise and headache. Fever and tachycardia resolved over the next 12 hours, with weakness and headache resolving within 1-2 days. His symptom complex was consistent with the Jarisch-Herxheimer reaction. Histopathology of skin biopsy of the back showed perivascular inflammation and rare spirochetes, consistent with secondary syphilis. The patient completed 14 days of aqueous crystalline penicillin G and was discharged after receiving the first of three benzathine penicillin injections. DISCUSSION: The initial manifestations of syphilis in this patient were posterior uveitis and pruritic skin plaques. His diagnosis should be appropriately classified as secondary syphilis with concomitant symptomatic early neurosyphilis, requiring 14 days of aqueous crystalline penicillin G. This type of presentation is not specific to immunocompromised populations and must be considered even in the general population. Making the diagnosis of early neurosyphilis, regardless of stage, is critical, as it necessitates a longer duration of treatment. Furthermore, clinicians should be reminded of the profound immunologic reaction, Jarisch-Herxheimer, which may occur when treating any treponemal disease.

Acute traumatic coagulopathy: pathophysiology and resuscitation.

Acute Traumatic Coagulopathy occurs immediately after massive trauma when shock, hypoperfusion, and vascular damage are present. Mechanisms for this acute coagulopathy include activation of protein C, endothelial glycocalyx disruption, depletion of fibrinogen, and platelet dysfunction. Hypothermia and acidaemia amplify the endogenous coagulopathy and often accompany trauma. These multifactorial processes lead to decreased clot strength, autoheparinization, and hyperfibrinolysis. Furthermore, the effects of aggressive crystalloid administration, haemodilution from inappropriate blood product transfusion, and prolonged surgical times may worsen clinical outcomes. We review normal coagulation using the cell-based model of haemostasis and the pathophysiology of acute traumatic coagulopathy. Developed trauma systems reduce mortality, highlighting critical goals for the trauma patient in different phases of care. Once patients reach a trauma hospital, certain triggers reliably indicate when they require massive transfusion and specialized trauma care. These triggers include base deficit, international normalized radio (INR), systolic arterial pressure, haemoglobin concentration, and temperature. Early identification for massive transfusion is critically important, as exsanguination in the first few hours of trauma is a leading cause of death. To combat derangements caused by massive haemorrhage, damage control resuscitation is a technique that addresses each antagonist to normal haemostasis. Components of damage control resuscitation include damage control surgery, permissive hypotension, limited crystalloid administration, haemostatic resuscitation, and correction of hyperfibrinolysis.

Functional brain-imaging correlates of negative affectivity and the onset of first-episode depression.

BACKGROUND: The amygdala and subgenual anterior cingulate cortex (sACC) are key brain regions for the generation of negative affect. In this longitudinal fMRI study of adolescents we investigated how amygdala-sACC connectivity was correlated with negative affectivity (NA) both cross-sectionally and longitudinally, and examined its relationship to the onset of first-episode depression. METHOD: Fifty-six adolescents who were part of a larger longitudinal study of adolescent development were included. They had no history of mental illness at the time of their baseline scan (mean age 16.5 years) and had a follow-up scan 2 years later (mean age 18.8 years). We used resting-state functional-connectivity MRI to investigate whether cross-sectional and change measures of amygdala-sACC connectivity were (i) correlated with NA and its change over time, and (ii) related to the onset of first-episode depression. RESULTS: The magnitude of amygdala connectivity with sACC showed significant positive correlation with NA at both time-points. Further analysis confirmed that change in amygdala-sACC connectivity between assessments was correlated with change in NA. Eight participants developed a first episode of depression between the baseline and follow-up assessments: they showed increased amygdala-sACC connectivity at follow-up. CONCLUSIONS: Amygdala-sACC connectivity is associated with NA in adolescence, with change in connectivity between these regions showing positive correlation with change in NA. Our observation that the onset of depression was associated with an increase in connectivity between the regions provides support for the neurobiological 'scar' hypothesis of depression.

Animal Models of Bone Metastasis.

Bone is one of the most common sites of cancer metastasis in humans and is a significant source of morbidity and mortality. Bone metastases are considered incurable and result in pain, pathologic fracture, and decreased quality of life. Animal models of skeletal metastases are essential to improve the understanding of the molecular pathways of cancer metastasis and growth in bone and to develop new therapies to inhibit and prevent bone metastases. The ideal animal model should be clinically relevant, reproducible, and representative of human disease. Currently, an ideal model does not exist; however, understanding the strengths and weaknesses of the available models will lead to proper study design and successful cancer research. This review provides an overview of the current in vivo animal models used in the study of skeletal metastases or local tumor invasion into bone and focuses on mammary and prostate cancer, lymphoma, multiple myeloma, head and neck squamous cell carcinoma, and miscellaneous tumors that metastasize to bone.

Development, reliability and validity of the queensland evaluation of wheelchair skills (QEWS).

STUDY DESIGN: Psychometric studyObjectives:To develop and test a valid and reliable assessment of wheelchair skills for individuals with spinal cord injuries (SCI); the Queensland Evaluation of Wheelchair Skills (QEWS). SETTING: Hospital, Australia. METHODS: Phase 1: Four Delphi panel rounds with clinical experts were used to develop the QEWS. Phase 2: Intra-rater and inter-rater reliability of the QEWS items were examined in 100 people with SCI. Phase 3a: Concurrent validity was investigated by examining the association between QEWS total scores and physiotherapists' global ratings of wheelchair skill performance. Phase 3b: Construct validity was tested in 20 people with recent SCI by examining change in QEWS total scores between when they first mobilised in a wheelchair and scores obtained 10 weeks later. RESULTS: Phase 1: The QEWS was developed. Phase 2: The intra-class correlation coefficients reflecting the intra-rater reliability and the inter-rater reliability for the QEWS total score were 1.00 and 0.98, with scores being within one point of each other 96 and 91% of the time, respectively. Phase 3a: The QEWS total scores were comparable with the global rating of wheelchair skill performance (r2=0.93). Phase 3b: The QEWS scores changed by a median (interquartile range (IQR)) of 4 (1 to 6) points over the 10-week period following first wheelchair mobilisation. CONCLUSION: The QEWS is a valid and reliable tool for measuring wheelchair skills in individuals with SCI. The QEWS is efficient and practical to administer and does not require specialised equipment.

Fused polycyclic compounds via cycloaddition of 4-(1'-cyclohexenyl)-5-iodo-1,2,3-triazoles with 4-phenyl-1,2,4-triazoline-3,5-dione: the importance of a sacrificial iodide leaving group.

4-(1'-Cyclohexenyl)-5-iodo-1,2,3-triazole and 4-phenyl-1,2,4-triazoline-3,5-dione undergo a formal Diels-Alder reaction, which following an S(N)2' solvolysis process to displace the iodo group affords a fused polycyclic compound.