A 0.6 Mpc H I structure associated with Stephan's Quintet.

Stephan's Quintet (SQ, co-moving radial distance = 85 ± 6 Mpc, taken from the NASA/IPAC Extragalactic Database (NED)1) is unique among compact groups of galaxies2-12. Observations have previously shown that interactions between multiple members, including a high-speed intruder galaxy currently colliding into the intragroup medium, have probably generated tidal debris in the form of multiple gaseous and stellar filaments6,8,13, the formation of tidal dwarfs7,14,15 and intragroup-medium starbursts16, as well as widespread intergalactic shocked gas5,10,11,17. The details and timing of the interactions and collisions remain poorly understood because of their multiple nature18,19. Here we report atomic hydrogen (H I) observations in the vicinity of SQ with a smoothed sensitivity of 1σ = 4.2 × 1016 cm-2 per channel (velocity bin-width Δv = 20 km s-1; angular resolution = 4'), which are about two orders of magnitude deeper than previous observations8,13,20,21. The data show a large H I structure (with linear scale of around 0.6 Mpc) encompassing an extended source of size approximately 0.4 Mpc associated with the debris field and a curved diffuse feature of length around 0.5 Mpc attached to the south edge of the extended source. The diffuse feature was probably produced by tidal interactions in early stages of the formation of SQ (>1 Gyr ago), although it is not clear how the low-density H I gas (NH i ≲ 1018 cm-2) can survive the ionization by the intergalactic ultraviolet background on such a long time scale. Our observations require a rethinking of properties of gas in outer parts of galaxy groups and demand complex modelling of different phases of the intragroup medium in simulations of group formation.

Comparison of outcomes of operative versus non-operative treatment of acetabular fractures in the elderly and severely comorbid patient.

BACKGROUND: Acetabular fractures in the elderly and severely comorbid patient can be associated with high morbidity and mortality; however, differences in outcomes of acute ORIF versus non-operative care of acetabular fractures in a subgroup of elderly (>75 years) and/or severely comorbid younger patients (>65) remain unclear. PATIENTS AND METHODS: A retrospective review of 243 patients who sustained an acetabular fracture between April 2005 and November 2014 was performed. Eighty-seven patients met inclusion criteria: age > 75 with or without comorbidities or age > 65 if complicated by two or more medical comorbidities. Outcomes measures evaluated were 1-year mortality, duration of hospital stay, return to pre-injury ambulation status and treatment failure marked by conversion to a total hip arthroplasty (THA) within 1 year of treatment. RESULTS: Thirty-seven patients with acetabular fractures were treated with surgical fixation, and 49 were treated non-operatively. Operative patients did not demonstrate a statistically significant difference in mortality within 1 year of treatment compared to non-operatively treated patients. Operative patients demonstrated a statistically significant increase in treatment failure marked by a conversion to a THA within 1 year when compared to conservatively treated patients. No differences in age, duration of follow-up, or ability to return to baseline at latest clinical follow-up were found between groups. However, non-operatively treated patients had a higher incidence of Alzheimer's disease/Dementia and Parkinson's compared to operatively treated patients. CONCLUSION: Analysis of our small cohort suggests that there may be a role for the non-operative treatment of acetabular fractures in this debilitated patient population despite a somewhat longer length of hospital stay at the time of injury. Conversion to THA was significantly higher at 1 year in our operated patients. No differences in mortality at 1 year were noted between patient groups. Return to baseline ambulation status was slightly higher in the non-operated group but not significantly so. However, a potential bias to more likely treat complex fractures operatively cannot be ruled out, as non-operative fractures were most often anterior column variants, usually more amenable to non-operative care. LEVEL OF EVIDENCE: Prognostic Level III.

A prospective randomised controlled trial of the fibular nail versus standard open reduction and internal fixation for fixation of ankle fractures in elderly patients.

AIMS: The fundamental concept of open reduction and internal fixation (ORIF) of ankle fractures has not changed appreciably since the 1960s and, whilst widely used, is associated with complications including wound dehiscence and infection, prominent hardware and failure. Closed reduction and intramedullary fixation (CRIF) using a fibular nail, wires or screws is biomechanically stronger, requires minimal incisions, and has low-profile hardware. We hypothesised that fibular nailing in the elderly would have similar functional outcomes to standard fixation, with a reduced rate of wound and hardware problems. PATIENTS AND METHODS: A total of 100 patients (25 men, 75 women) over the age of 65 years with unstable ankle fractures were randomised to undergo standard ORIF or fibular nailing (11 men and 39 women in the ORIF group, 14 men and 36 women in the fibular nail group). The mean age was 74 years (65 to 93) and all patients had at least one medical comorbidity. Complications, patient related outcome measures and cost-effectiveness were assessed over 12 months. RESULTS: Significantly fewer wound infections occurred in the fibular nail group (p = 0.002). At one year, there was no evidence of difference in mean functional scores (Olerud and Molander Scores 63; 30 to 85, versus 61; 10 to 35, p = 0.61) or scar satisfaction. The overall cost of treatment in the fibular nail group was £91 less than in the ORIF group despite the higher initial cost of the implant. CONCLUSION: We conclude that the fibular nail allows accurate reduction and secure fixation of ankle fractures, with a significantly lower rate of soft-tissue complications, and is more cost-effective than ORIF. Cite this article: Bone Joint J 2016;98-B:1248-52.

Increased variability in Apc(Min)/+ intestinal tissue can be measured with microultrasound.

Altered tissue structure is a feature of many disease states and is usually measured by microscopic methods, limiting analysis to small areas. Means to rapidly and quantitatively measure the structure and organisation of large tissue areas would represent a major advance not just for research but also in the clinic. Here, changes in tissue organisation that result from heterozygosity in Apc, a precancerous situation, are comprehensively measured using microultrasound and three-dimensional high-resolution microscopy. Despite its normal appearance in conventionally examined cross-sections, both approaches revealed a significant increase in the variability of tissue organisation in Apc heterozygous tissue. These changes preceded the formation of aberrant crypt foci or adenoma. Measuring these premalignant changes using microultrasound provides a potential means to detect microscopically abnormal regions in large tissue samples, independent of visual examination or biopsies. Not only does this provide a powerful tool for studying tissue structure in experimental settings, the ability to detect and monitor tissue changes by microultrasound could be developed into a powerful adjunct to screening endoscopy in the clinic.

Combined changes in Wnt signaling response and contact inhibition induce altered proliferation in radiation-treated intestinal crypts.

Curative intervention is possible if colorectal cancer is identified early, underscoring the need to detect the earliest stages of malignant transformation. A candidate biomarker is the expanded proliferative zone observed in crypts before adenoma formation, also found in irradiated crypts. However, the underlying driving mechanism for this is not known. Wnt signaling is a key regulator of proliferation, and elevated Wnt signaling is implicated in cancer. Nonetheless, how cells differentiate Wnt signals of varying strengths is not understood. We use computational modeling to compare alternative hypotheses about how Wnt signaling and contact inhibition affect proliferation. Direct comparison of simulations with published experimental data revealed that the model that best reproduces proliferation patterns in normal crypts stipulates that proliferative fate and cell cycle duration are set by the Wnt stimulus experienced at birth. The model also showed that the broadened proliferation zone induced by tumorigenic radiation can be attributed to cells responding to lower Wnt concentrations and dividing at smaller volumes. Application of the model to data from irradiated crypts after an extended recovery period permitted deductions about the extent of the initial insult. Application of computational modeling to experimental data revealed how mechanisms that control cell dynamics are altered at the earliest stages of carcinogenesis.

The treatment of unstable fractures of the ankle using the Acumed fibular nail: development of a technique.

Techniques for fixation of fractures of the lateral malleolus have remained essentially unchanged since the 1960s, but are associated with complication rates of up to 30%. The fibular nail is an alternative method of fixation requiring a minimal incision and tissue dissection, and has the potential to reduce the incidence of complications. We reviewed the results of 105 patients with unstable fractures of the ankle that were fixed between 2002 and 2010 using the Acumed fibular nail. The mean age of the patients was 64.8 years (22 to 95), and 80 (76%) had significant systemic medical comorbidities. Various different configurations of locking screw were assessed over the study period as experience was gained with the device. Nailing without the use of locking screws gave satisfactory stability in only 66% of cases (4 of 6). Initial locking screw constructs rendered between 91% (10 of 11) and 96% (23 of 24) of ankles stable. Overall, seven patients had loss of fixation of the fracture and there were five post-operative wound infections related to the distal fibula. This lead to the development of the current technique with a screw across the syndesmosis in addition to a distal locking screw. In 21 patients treated with this technique there have been no significant complications and only one superficial wound infection. Good fracture reduction was achieved in all of these patients. The mean physical component Short-Form 12, Olerud and Molander score, and American Academy of Orthopaedic Surgeons Foot and Ankle outcome scores at a mean of six years post-injury were 46 (28 to 61), 65 (35 to 100) and 83 (52 to 99), respectively. There have been no cases of fibular nonunion. Nailing of the fibula using our current technique gives good radiological and functional outcomes with minimal complications, and should be considered in the management of patients with an unstable ankle fracture.

Defining the role of APC in the mitotic spindle checkpoint in vivo: APC-deficient cells are resistant to Taxol.

Mutations in the adenomatous polyposis coli (APC) tumour suppressor are the key initiating event of colorectal cancer. Although the control of WNT signalling is well established as a central tumour-suppressive function, the significance of APC in regulating chromosome instability is less well established. In this study, we test whether APC-deficient cells have a functional spindle assembly checkpoint (SAC) in vivo by examining the response of these cells to Taxol and Vinorelbine. We also show for the first time that APC deficiency compromises the arrest response to Taxol in vivo. This effect is independent of the role that APC has in WNT signalling. At higher levels of Taxol, APC-deficient cells arrest as efficiently as wild-type cells. Importantly, this dose of Taxol strongly suppresses intestinal tumourigenesis in models of benign (APC(Min/+) mouse) and invasive (AhCreER(+)APC(fl/+)PTEN(fl/fl)) cancer. In contrast to intestinal enterocytes with a general SAC defect because of Bub1 (budding uninhibited by benzimidazole 1) deletion, APC-deficient enterocytes arrest equivalently to wild type when treated with Vinorelbine. This suggests that the failed arrest in response to Taxol is because of a specific defect in microtubule stabilization following Taxol treatment rather than a general role of the APC protein in the mitotic spindle checkpoint. In summary, this study clarifies the role of APC as a mitotic spindle checkpoint protein in vivo and shows that APC-deficient cells have a compromised response to Taxol.

Preparation of wholemount mouse intestine for high-resolution three-dimensional imaging using two-photon microscopy.

Visualizing overall tissue architecture in three dimensions is fundamental for validating and integrating biochemical, cell biological and visual data from less complex systems such as cultured cells. Here, we describe a method to generate high-resolution three-dimensional image data of intact mouse gut tissue. Regions of highest interest lie between 50 and 200 mum within this tissue. The quality and usefulness of three-dimensional image data of tissue with such depth is limited owing to problems associated with scattered light, photobleaching and spherical aberration. Furthermore, the highest-quality oil-immersion lenses are designed to work at a maximum distance of

Distal femoral fractures treated by hinged total knee replacement in elderly patients.

Although the use of constrained cemented arthroplasty to treat distal femoral fractures in elderly patients has some practical advantages over the use of techniques of fixation, concerns as to a high rate of loosening after implantation of these prostheses has raised doubts about their use. We evaluated the results of hinged total knee replacement in the treatment of 54 fractures in 52 patients with a mean age of 82 years (55 to 98), who were socially dependent and poorly mobile. Within the first year after implantation 22 of the 54 patients had died, six had undergone a further operation and two required a revision of the prosthesis. The subsequent rate of further surgery and revision was low. A constrained knee prosthesis offers a useful alternative treatment to internal fixation in selected elderly patients with these fractures, and has a high probability of surviving as long as the patient into whom it has been implanted.

Histological effects in the iris after 3 months of latanoprost therapy: the Mainz 1 study.

OBJECTIVE: To determine whether 3 months of topical latanoprost treatment caused proliferative or degenerative effects on the peripheral iris of patients with glaucoma. METHODS: Seventeen patients requiring filtering surgery for primary open-angle glaucoma or pseudoexfoliation glaucoma were randomized to receive topical latanoprost for 3 months (n = 8) or alternative medication (n = 9) before surgery. A trabeculectomy and a peripheral iridectomy specimen was obtained from each patient during surgery. The tissue was subjected to histological and immunohistochemical evaluation using 2 cell cycle markers: proliferating cell nuclear antigen and nuclear-associated protein (Ki-67). RESULTS: No degenerative or pathological changes were seen in the latanoprost-treated irides, including the one specimen in this series in which there was an eye color change. Proliferating cell nuclear antigen and nuclear-associated protein markers were negative for changes in all the test specimens. CONCLUSION: Short-term treatment with latanoprost does not produce morphological changes or cellular proliferation changes in the iris.

Apoptosis in multinucleated skeletal muscle myotubes.

Several recent studies report endonuclease-mediated DNA degradation as evidence of apoptotic degeneration of skeletal muscle in the muscular dystrophies and other muscle disorders. Interpretation of the results of such studies is complicated by the ubiquitous presence of non-muscle cells within muscle in vivo and by a lack of knowledge concerning the nature of the process of apoptosis in postmitotic, multinucleated skeletal muscle and the potential mechanisms involved. Staurosporine treatment of C2C12 skeletal muscle myotubes induced several classic features of apoptosis, including cell and nuclear shrinkage with initial preservation of cellular membranes. Externalization of phosphatidylserine occurred within 2 hours of treatment, and myotubes contained procaspase 3, which seemed to be activated within 4 hours. DNA degradation was identified by transferase uridine triphosphate nick-end labeling within 4 hours, and DNA ladders were identified on agarose electrophoresis of genomic DNA within 8 hours. Thus, the process of apoptosis in postmitotic multinucleated skeletal muscle shares many of the characteristics of apoptosis in mononuclear mitotic cells. However, the pattern of degeneration does not seem to be compatible with that seen in the muscular dystrophies.

A case of ventricular fibrillation in the prone position during back stabilisation surgery in a boy with Duchenne's muscular dystrophy.

A 15-year-old boy with Duchenne's muscular dystrophy experienced prolonged cardiac arrest whilst in the prone position for spinal surgery. He was successfully resuscitated without apparent neurological sequelae by internal cardiac massage via a thoracotomy and external and internal direct current cardioversion. Recommendations are suggested for the pre- and peroperative management of such cases.

Stress and avoidance in Pseudoseizures: testing the assumptions.

Twenty women and 10 men with Pseudoseizures were matched by age and gender with an epilepsy- and a healthy-control group. In response to clinical and research evidence of a relationship between Pseudoseizures and the experience of stress, it was hypothesised that people with Pseudoseizures would perceive their ongoing lives as more stressful, and use more avoidant and distancing coping, and less problem-focused coping, than people in the two control groups. Using the Perceived Stress Scale (Cohen et al., J. Health Soc. Behav. 24, 1983, 385-396) and the Ways of Coping, revised version (Folkman and Lazarus, Manual for Ways of Coping Questionnaire, Consulting Psychologist Press, Paola Alto, CA, 1988) the study found that people with Pseudoseizures: (1) perceived their ongoing lives as significantly more stressful; (2) were significantly more likely to use a maladaptive (escape-avoidant) coping strategy; and (3) were significantly less likely to use an adaptive (planful problem solving) approach to coping than healthy controls. The study findings indicate that people with Pseudoseizures experience lives as stressful as do people with epilepsy, and are likely to employ maladaptive coping responses. Implications for diagnosis, intervention and future research are discussed.

Edible mushroom (Agaricus bisporus) lectin, which reversibly inhibits epithelial cell proliferation, blocks nuclear localization sequence-dependent nuclear protein import.

The Galbeta1-3GalNAcalpha (TF antigen)-binding lectin (ABL) from the common edible mushroom (Agaricus bisporus) has a potent anti-proliferative effect without any apparent cytotoxicity. This unusual combination of properties prompted investigation of its mechanism of action. In contrast to soluble lectin, agarose-immobilized, and hence noninternalizable ABL had no effect on proliferation of HT29 colon cancer cells. Electron microscopy of HT29 cells incubated with fluorescein- and gold-conjugated ABL showed internalization of the lectin into endocytotic vesicles and multivesicular bodies. Confocal microscopy showed perinuclear accumulation of fluorescein isothiocyanate-conjugated lectin, which also inhibits HT29 cell proliferation, raising the possibility that the lectin might interfere with nuclear pore function. Transport of heat shock protein 70 into the nucleus in response to heat shock was blocked by preincubation of HT29 cells for 6 h with 40 micrograms/ml ABL. In digitonin-permeabilized cells, nuclear uptake of bovine albumin conjugated to a nuclear localization sequence (NLS)-containing peptide was also inhibited by a 15-min preincubation with 40-100 micrograms/ml ABL. In contrast, serum-stimulated nuclear translocation of mitogen-activated protein kinase, which is NLS-independent, was not affected by pretreatment of cells with the lectin. These results suggest that the anti-proliferative effect of ABL is likely to be a consequence of the lectin trafficking to the nuclear periphery, where it blocks NLS-dependent protein uptake into the nucleus.

In vitro cultivation and developmental cycle in culture of a parasitic dinoflagellate (Hematodinium sp.) associated with mortality of the Norway lobster (Nephrops norvegicus) in British waters.

Dinoflagellates are common and often important parasites of aquatic organisms, but their developmental cycles are poorly known and have not been established in in vitro culture. The parasitic dinoflagellate (Hematodinium sp.) associated with mortality of the Norway lobster (Nephrops norvegicus) in British waters has been cultivated in vitro in 10% foetal calf serum in a balanced Nephrops saline. In culture the parasite undergoes a characteristic cycle of development. Circulating sporoblasts from the host's haemolymph in vitro generate 2 kinds of flagellated uninucleate dinospore, macrospores and microspores, either of which will, after 5 weeks in fresh medium, germinate to produce multinucleate unattached filamentous trophonts. These trophonts multiply by fragmentation and growth and may be serially subcultured in this form, at 2 week intervals, indefinitely. If not subcultured, the filamentous trophonts give rise to colonies of radiating filaments ('gorgonlocks') which subsequently attach to the substratum to form flattened web-like 'arachnoid' multinucleate trophonts. Arachnoid trophonts become arachnoid sporonts when they synthesize trichocysts and flagellar hairs and may give rise to secondary arachnoid sporonts or to dinospores which initiate a new cycle.

Beyond child development centres: care coordination for children with disabilities.

A specific model of care coordination for children with disabilities is described, comprising parental empowerment, a defined client population, individual tailoring of service based on assessment of need, inter-agency collaboration beyond existing team boundaries, continuity of named professional contact across transitions important to families, and a named care coordinator. The first stages of local implementation of the model are described for children with a disability making the transition into nursery school provision. Qualitative findings from interviews with families and care coordinators are presented, and the possibility of care coordinators providing a Named Person function is examined.

Depressive symptoms and self-concept in young people with spina bifida.

Examined self-reported depressive symptoms in 72 young people with spina bifida, ages 9 to 18:11, and matched able-bodied comparison subjects, using the Dimensions of Depression Profile for Children and Adolescents (Harter & Nowakowski, 1987). Independent variables included gender, self-perceptions (including physical appearance), and perceived social support. Young people with spina bifida were at greater risk of depressive mood, low self-worth, and suicidal ideation. Girls, independent of disability, were at greater risk of depressive mood, low self-worth, and self-blame. Multiple regression analyses suggest that global self-worth serves as a mediating variable for the effect of physical appearance self-concept on depressed mood (particularly in young people with spina bifida), and that perceived parental social support has a direct effect on depressed mood (particularly in girls).