Spectroscopic identification of water emission from a main-belt comet.

Main-belt comets are small Solar System bodies located in the asteroid belt that repeatedly exhibit comet-like activity (that is, dust comae or tails) during their perihelion passages, strongly indicating ice sublimation1,2. Although the existence of main-belt comets implies the presence of extant water ice in the asteroid belt, no gas has been detected around these objects despite intense scrutiny with the world's largest telescopes3. Here we present James Webb Space Telescope observations that clearly show that main-belt comet 238P/Read has a coma of water vapour, but lacks a significant CO2 gas coma. Our findings demonstrate that the activity of comet Read is driven by water-ice sublimation, and implies that main-belt comets are fundamentally different from the general cometary population. Whether or not comet Read experienced different formation circumstances or evolutionary history, it is unlikely to be a recent asteroid belt interloper from the outer Solar System. On the basis of these results, main-belt comets appear to represent a sample of volatile material that is currently unrepresented in observations of classical comets and the meteoritic record, making them important for understanding the early Solar System's volatile inventory and its subsequent evolution.

A rapid decrease in the rotation rate of comet 41P/Tuttle-Giacobini-Kresák.

Cometary outgassing can produce torques that change the spin state of the cometary nucleus, which in turn influences the evolution and lifetime of the comet. If these torques increase the rate of rotation to the extent that centripetal forces exceed the material strength of the nucleus, the comet can fragment. Torques that slow down the rotation can cause the spin state to become unstable, but if the torques persist the nucleus can eventually reorient itself and the rotation rate can increase again. Simulations predict that most comets go through a short phase of rapid changes in spin state, after which changes occur gradually over longer times. Here we report observations of comet 41P/Tuttle-Giacobini-Kresák during its close approach to Earth (0.142 astronomical units, approximately 21 million kilometres, on 1 April 2017) that reveal a rapid decrease in rotation rate. Between March and May 2017, the apparent rotation period of the nucleus increased from 20 hours to more than 46 hours-a rate of change of more than an order of magnitude larger than has hitherto been measured. This phenomenon must have been caused by the gas emission from the comet aligning in such a way that it produced an anomalously strong torque that slowed the spin rate of the nucleus. The behaviour of comet 41P/Tuttle-Giacobini-Kresák suggests that it is in a distinct evolutionary state and that its rotation may be approaching the point of instability.

Do All X-ray Structures of Protein-Ligand Complexes Represent Functional States? EPOR, a Case Study.

Based on differences between the x-ray crystal structures of ligand-bound and unbound forms, the activation of the erythropoietin receptor (EPOR) was initially proposed to involve a cross-action scissorlike motion. However, the validity of the motions involved in the scissorlike model has been recently challenged. Here, atomistic molecular dynamics simulations are used to examine the structure of the extracellular domain of the EPOR dimer in the presence and absence of erythropoietin and a series of agonistic or antagonistic mimetic peptides free in solution. The simulations suggest that in the absence of crystal packing effects, the EPOR chains in the different dimers adopt very similar conformations with no clear distinction between the agonist and antagonist-bound complexes. This questions whether the available x-ray crystal structures of EPOR truly represent active or inactive conformations. The study demonstrates the difficulty in using such structures to infer a mechanism of action, especially in the case of membrane receptors where just part of the structure has been considered in addition to potential confounding effects that arise from the comparison of structures in a crystal as opposed to a membrane environment. The work highlights the danger of assigning functional significance to small differences between structures of proteins bound to different ligands in a crystal environment without consideration of the effects of the crystal lattice and thermal motion.

Revisiting the scissor-like mechanism of activation for the erythropoietin receptor.

An interpretation of alternative crystal structures of the erythropoietin receptor, with and without ligand, led to the proposal of a scissor-like mechanism of activation. This model has been propagated in the literature and is still being used to interpret crystal structures of related type-I cytokine receptors. Here, we assess whether the model remains compatible with current knowledge on the family of type-I cytokine receptors, and consider whether the model, as initially presented, is truly supported by the crystal structures on which it was originally based.

Effect of arm position and foot placement on the five times sit-to-stand test completion times of female adults older than 50 years of age.

The five times-sit-to stand test (FTSTS) is a clinical test which is commonly used to assessed the functional muscle strength of the lower limbs of older adults. The aim of this study was to examine the effect of different arm positions and foot placements on the FTSTS completion times of older female adults. [Subjects and Methods] Twenty-nine healthy female subjects, aged 63.1±5.3 years participated in this cross-sectional study. The times required to complete the FTSTS with 3 different arm positions (hands on thighs, arms crossed over chest, and an augmented arm position with the arms extended forward) and 2 foot placements (neutral and posterior) were recorded. The interaction effect and main effect of arm positions and foot placements were examined using a 3 (arm position) × 2 (foot placement) two-way repeated measures analysis of variance (ANOVA). [Results] There was no interaction effect among the 3 arm positions in the 2 foot placements. A significant main effect was identified for foot placement, but not arm position. Posterior foot placement led to a shorter FTSTS time compared to that of normal foot placement. [Conclusion] With the same arm position, FTSTS completion times with posterior foot placement tended to be shorter. Therefore, the standard foot placement should be used for FTSTS administration.

Molecular modeling correctly predicts the functional importance of Phe594 in transmembrane helix 11 of the multidrug resistance protein, MRP1 (ABCC1).

The human ATP-binding cassette (ABC) transporter, multidrug resistance protein 1 (MRP1/ABCC1), confers resistance to a broad range of anti-cancer agents and transports a variety of organic anions. At present, essentially no structural data exists for MRP1 that might be used to elucidate its mechanism of transport. Consequently, we have applied a modeling strategy incorporating crystal and indirect structural data from other ABC transporters to construct a model of the transmembrane domains of the core region of MRP1 that includes the amino acid side chains. Three conserved Trp residues and one non-conserved Tyr residue, shown previously to be of functional importance (Koike, K., Oleschuk, C. J., Haimeur, A., Olsen, S. L., Deeley, R. G., and Cole, S. P. C. (2002) J. Biol. Chem. 277, 49495-49503), were found to line the "pore" in our model proximal to the membrane cytosol interface. A fifth aromatic residue (Phe594) was identified that, with the Trp and Tyr residues, completed a ring or "basket" of aromatic amino acids and, accordingly, we postulated that it would also be of functional importance. To test this idea, MRP1-Phe594 mutants were expressed in human embryonic kidney cells, and their properties were examined using membrane vesicles. Substitution of Phe594 with Ala substantially reduced or eliminated the transport of five organic anion substrates by MRP1 and abrogated the binding of leukotriene C4. On the other hand, the conservatively substituted F594W and F594Y mutants remained transport competent, although significant substrate- and substitution-specific changes were observed. These studies provide some structural insight into a possible substrate binding/transport site of MRP1 at the beginning of a putative substrate translocation pathway and demonstrate the usefulness of modeling for directing structure-function analyses of this transporter.

Fine needle aspiration in the management of benign thyroid cysts.

BACKGROUND: Resolution of cystic thyroid lesions after aspiration occurs in 8-45% of cases, the remainder require treatment for residual tumour or recurrent cysts. The aim of this study was to identify patient characteristics that predict cyst recurrence to enable these patients to undergo early surgery. METHODS: A retrospective analysis of 123 patients with benign thyroid cysts that were suitable for conservative management was undertaken. Demographic, clinical, ultrasound and fine needle aspiration cytology data were collated for patients who underwent surgery or were managed conservatively. Univariate and multivariate analyses were performed to identify factors predictive of cyst recurrence. RESULTS: Of the 123 patients, 43 underwent surgery consequent on cyst recurrence or persistent symptoms after aspiration, and 80 were treated by aspiration alone. There were 17 males and 106 females, of mean age 45.5 years. The mean cyst size was 27 mm. Those undergoing surgery had a significantly greater mean cyst size (P = 0.001). The only factor predicting cyst recurrence on univariate analysis was absence of follicular cells on initial aspiration (P = 0.005). Multivariate analysis confirmed absence of follicular cells as an independent characteristic predicting recurrence, the odds ratios for recurrence was 3.18 (95%CI 1.39-7.29). CONCLUSION: The present study suggests consideration of early surgery for patients with thyroid cysts with absence of follicular cells on initial cytology.

Fine-needle aspiration cytology of thyroid nodules: how useful is it?

BACKGROUND: Thyroid nodules are common and the principal method of diagnosis is fine-needle aspiration cytology (FNAC). METHODS: To determine the value of FNAC in the diagnosis of thyroid nodules, thyroid cytology of 253 patients with definitive histology after surgery was analyzed from 1992 to 2002. FNAC was correlated with histology and the sensitivity, specificity and likelihood ratios were calculated. The method of FNAC and number of non-diagnostic aspirates were noted. The frequency of thyroid cancer was investigated in male and females who presented with a solitary thyroid nodule. RESULTS: The overall sensitivity of FNAC detecting thyroid neoplasia was 55.0%, specificity 73.7% and accuracy 67.2%. Likelihood ratios indicate that a 'malignant' or 'suspicious for malignancy' cytology dramatically increase the pretest probability of thyroid neoplasia. There were no false positive 'malignant' FNAC. Ultrasound guided FNAC had a significantly lower non-diagnostic rate compared to freehand FNAC (P < 0.02). Of 22 males, 22.7% who proceeded to surgery for their solitary nodule had thyroid carcinoma compared with 11.9% of 167 females (P = 0.02). CONCLUSIONS: FNAC was essential to management in this series of patients. 'Malignant' or 'suspicious for malignancy' cytology are absolute indicators for thyroidectomy. FNAC should be undertaken with ultrasound guidance and if possible with a pathologist in attendance to assess sample adequacy. We recommend a high index of suspicion of thyroid cancer in the male patient who presents with a solitary nodule. If solitary nodules are to be observed, repeat FNAC should be undertaken because of the high false negative rate.

Impact of core biopsy on the management of screen-detected ductal carcinoma in situ of the breast.

BACKGROUND: Screen-detected ductal carcinoma in situ (DCIS) usually presents as clinically impalpable microcalcification. Although core biopsy is well established as a diagnostic modality for invasive breast cancers, few reports address its impact on the management of screen-detected DCIS. We examined the sensitivity of core biopsy in diagnosing screen-detected DCIS, as well as its role in facilitating one-step surgery in the community, especially a breast-conserving approach. METHODS: Through the Monash BreastScreen database, we reviewed the management of 148 patients diagnosed with pure DCIS over a 4-year period. Particular attention was paid to the sensitivity and surgical margin status of 63 patients who underwent initial assessment with core biopsy, compared to patients who underwent excisional biopsy or fine needle aspiration cytology (FNAC). RESULTS: Core specimens in 63 patients yielded positive histology in 57 (90%), allowing for breast-conserving surgery in 45 and mastectomy in 12. Negative margins were obtained in 73% of those treated by breast-conserving surgery, compared to 51% negative margins among those who underwent excisional biopsy initially. Overall, 45 of 57 patients with a positive core biopsy histology (79%) underwent one-step surgery. Those assessed by FNAC had a 48% incidence of non-diagnostic/benign cytology. CONCLUSIONS: Core biopsy facilitates one-step surgery for screen-detected DCIS, and potentially reduces the number of surgical procedures. Stereotactic core biopsy for suspicious microcalcifications should replace hookwire-guided excisional biopsy and FNAC as the diagnostic modality of choice.

Does frozen section have a role in the intraoperative management of thyroid nodules?

BACKGROUND: Frozen section in thyroid surgery is used to make an intraoperative pathological diagnosis of malignancy in a thyroid nodule at the time of hemithyroidectomy. A positive diagnosis allows completion of thyroidectomy, thus avoiding reoperation. However, the use of fine needle aspiration cytology in making a preoperative diagnosis of cancer has resulted in the lack of a defined role for frozen section. We examined the role of frozen section as an adjunct to fine needle aspiration cytology in determining which cytological subset will benefit from frozen section. METHODS: All patients who underwent thyroidectomy between 1992 and 2000 by a single endocrine surgeon were reviewed. RESULTS: Two hundred and nine frozen sections were performed, of which 144 underwent preoperative fine needle aspiration cytology. Frozen sections reported 135 benign nodules, 59 follicular neoplasms, five specimens with suspicious histology and 10 cancers. Ten out of 20 thyroid cancers were correctly identified by frozen section (sensitivity: 50%; specificity: 100%), eight cancers were reported on frozen section as indeterminate and two benign. Of 144 fine needle aspiration cytological procedures, frozen section on seven suspicious aspirates identified two cancers, and frozen section on 70 follicular aspirates identified four cancers, allowing intraoperative conversions to total thyroidectomy. Frozen section on seven malignant aspirates confirmed four cancers but resulted in reoperation for three because of the indeterminate frozen section reports. There were no cancers found on 135 benign aspirates. CONCLUSIONS: Frozen section on benign aspirates is unhelpful in the management of thyroid nodules. It need not be performed for cytologically proven malignant thyroid nodules. Selective use of frozen section complements fine needle aspiration cytology findings of suspicious or follicular lesions, especially in the subset with papillary cancer, allowing one-stage total thyroidectomy.

Anatomy and kinematics of the lateral collateral ligament of the knee.

The anatomy and kinematics of the lateral collateral ligament were studied in 10 unembalmed limbs and 20 isolated femurs and fibulas. The ligament's average overall length was 66 mm (range, 59 to 74) and the average greatest dimension of its thin middle portion was the anteroposterior dimension of 3.4 mm (range, 3 to 4). The center of the femoral attachment site was 3.7 mm posterior to the ridge of the lateral epicondyle, not at it apex. A potential radiographic technique for operatively locating the femoral attachment site to within 3 mm is described. During knee flexion in neutral rotation the distance between the femoral and fibular attachment sites of the lateral collateral ligament decreased to 88% of its value in full extension. With 6.5 N x m of applied external rotation force, beyond 30 degrees of flexion the attachment sites rapidly approximated. With the same internal rotation force, beyond 15 degrees of flexion the attachment sites separated. From 60 degrees to 105 degrees they were greater than 100% of the value in full extension, suggesting significant distraction between the attachment sites. These changes correlated well with the ligament's change from an 11 degrees posterior slope in extension to a 19 degrees anterior slope in flexion with no applied rotation.

Localization of the ulnar nerve during percutaneous wiring of supracondylar fractures in children.

Injury of the ulnar nerve may occur when using percutaneous Kirschner wires (K-wires) in the treatment of supracondylar humeral fractures of the elbow especially in children whose bony landmarks are masked by swelling. We describe a technique in which this complication can be avoided during the procedure. The nerve is located first using a needle attached to a nerve stimulator. The K-wire is then inserted 0.5 to 0.75 mm anterior and parallel to the needle. Ten supracondylar fractures of the humerus were stabilized using this procedure and there were no ulnar nerve complications.

The diagnostic yield of only one occipito-mental radiograph in cases of suspected midfacial trauma--or is one enough?

The number of radiographic examinations should be reduced to clinical needs. Often in cases of suspected midfacial injury three views comprise a routine 'facial view' survey. A reduction in patient radiation exposure and X-ray costs would be achieved if only one occipito-mental radiograph was used. In this study the ability of Accident and Emergency staff to diagnose the presence of fractures using the standard occipito-mental view was assessed. The specificity value was 90% and the sensitivity was 75%. Few fractures were missed on initial scrutiny and in cases of doubt further views would be requested. Therefore the findings would suggest that only one view is sufficient for routine assessment.