Strong and deep Atlantic meridional overturning circulation during the last glacial cycle.

Extreme, abrupt Northern Hemisphere climate oscillations during the last glacial cycle (140,000 years ago to present) were modulated by changes in ocean circulation and atmospheric forcing. However, the variability of the Atlantic meridional overturning circulation (AMOC), which has a role in controlling heat transport from low to high latitudes and in ocean CO2 storage, is still poorly constrained beyond the Last Glacial Maximum. Here we show that a deep and vigorous overturning circulation mode has persisted for most of the last glacial cycle, dominating ocean circulation in the Atlantic, whereas a shallower glacial mode with southern-sourced waters filling the deep western North Atlantic prevailed during glacial maxima. Our results are based on a reconstruction of both the strength and the direction of the AMOC during the last glacial cycle from a highly resolved marine sedimentary record in the deep western North Atlantic. Parallel measurements of two independent chemical water tracers (the isotope ratios of (231)Pa/(230)Th and (143)Nd/(144)Nd), which are not directly affected by changes in the global cycle, reveal consistent responses of the AMOC during the last two glacial terminations. Any significant deviations from this configuration, resulting in slowdowns of the AMOC, were restricted to centennial-scale excursions during catastrophic iceberg discharges of the Heinrich stadials. Severe and multicentennial weakening of North Atlantic Deep Water formation occurred only during Heinrich stadials close to glacial maxima with increased ice coverage, probably as a result of increased fresh-water input. In contrast, the AMOC was relatively insensitive to submillennial meltwater pulses during warmer climate states, and an active AMOC prevailed during Dansgaard-Oeschger interstadials (Greenland warm periods).

[Rotator cuff tear : Indications and pathology-specific reconstructive procedures]. / Rotatorenmanschettenruptur : Indikationen und pathologiespezifische rekonstruktive Verfahren.

Rotator cuff (RC) tears comprise a broad spectrum of lesions ranging from partial to full thickness tears of a single tendon and massive cuff tears. Both glenohumeral trauma as well as degenerative processes can result in tearing of the RC. Treatment therefore requires a meticulous diagnosis as well as a differentiated approach by careful consideration of morphological and patient-specific factors. The pathogenesis, tear morphology, clinical symptoms and functional demands of the patient determine the therapeutic approach. Despite pathological and individual patient-related factors, early surgical repair is generally recommended for traumatic RC tears in young patients and in patients with high functional demands due to the high risk of tear progression. The results of RC repair are negatively correlated with the size of the lesion, the number of tendons involved, the degree of tendon retraction, muscular alteration and patient age. This article provides an overview of the various pathogenesis, indications and surgical repair of RC tears with respect to modern pathology-specific reconstructive procedures.

How do patients trade-off surgeon choice and waiting times for total joint replacement: a discrete choice experiment.

OBJECTIVE: Patients face significant waiting times for hip and knee total joint replacement (TJR) in publicly funded healthcare systems. We aimed to assess how surgeon selection and reputation affect patients' willingness to wait for TJR. DESIGN: We assessed patient preferences using a discrete choice experiment questionnaire with 12 choice scenarios administered to patients referred for TJR. Based on qualitative research, pre- and pilot-testing, we characterized each scenario by five attributes: surgeon reputation, surgeon selection, waiting time to surgeon visit (initial consultation), waiting time to surgery, and travel time to hospital. Preferences were assessed using hierarchical Bayes (HB) analysis and evaluated for goodness-of-fit. We conducted simulation analyses to understand how patients value surgeon reputation and surgeon selection in terms of willingness to wait for surgeon visit and surgery. RESULTS: Of 422 participants, 68% were referred for knee TJR. The most important attribute was surgeon reputation followed by waiting times, surgeon selection process and travel time. Patients appear willing to wait 10 months for a visit with an excellent reputation surgeon before switching to a good reputation surgeon. Patients in the highest pain category were willing to wait 7.3 months before accepting the next available surgeon, compared to 12 months for patients experiencing the least pain. CONCLUSIONS: Our findings confirm that patients value surgeon reputation in the context of wait times and surgeon selection. We suggest opportunities to reduce wait times by explicitly offering the next available surgeon to increase patient choice, and by reporting surgeon performance to reduce potential misinformation about reputation.

Bone-mediated anteroinferior glenohumeral instability : Current concepts.

Recurrent anterior shoulder instability is commonly associated with defects of the anterior glenoid rim. Substantial osseous defects significantly diminish the glenohumeral stability and require a bony augmentation, either by a coracoid transfer or free bone grafting procedure. Both reconstructive techniques have been applied for a long time and evaluated biomechanically and clinically. Although neither treatment option has been recognized as clearly superior, both comprise certain advantages and disadvantages. The Latarjet technique enables a biomechanically superior stabilization through the additional sling effect at time zero, but constitutes an extra-anatomical procedure with a broad spectrum and relatively high incidence of complications. Free bone grafting techniques enable an anatomical reconstruction of the glenoid concavity, offer the advantage of an unlimited graft size and show generally less severe and more easily manageable complications. The indications need to be carefully considered depending on the specific defect type, the glenoid track concept in cases of bipolar lesions as well as the individual patient characteristics. For both reconstructive procedures, open and arthroscopic approaches have been described with very good results, allowing a selection based on individual surgical skills and experience levels.

[Initial management of traumatic ventral shoulder dislocation]. / Initiales Management der traumatischen ventralen Schultererstluxation.

BACKGROUND: In the current literature a consensus on the specific management of primary anterior traumatic shoulder instability has not been reached. While the steps of the initial diagnostic and therapeutic procedures are mostly well-defined, a variety of factors need to be considered for the planning of further treatment. OBJECTIVE: This article aims at giving an overview of the essential aspects of the initial management in the rescue center, clinical and radiological diagnostic procedures and the subsequent treatment options. MATERIAL AND METHODS: The content of this article is based on our own clinical experiences in combination with a systematic literature search for relevant clinical and baseline studies. RESULTS: Besides a detailed anamnesis and clinical examination, X­rays in two planes are important for the diagnosis. Potential nerve injuries or fractures need to be borne in mind before and after reduction of the joint and documented accordingly. The Matsen's maneuver can be recommended as it enables a careful repositioning. In rare cases of an irreducible shoulder dislocation due to soft tissue or bony articular interpositions, an open reduction might be necessary. Further therapeutic concepts should be adapted to patient age, activity level and accompanying pathologies, which determine the risk of a recurrent dislocation. A surgical approach for stabilization of the shoulder is highly recommended in cases of concomitant bony defects as well as in young and physically active patients. CONCLUSION: A well-structured treatment plan is essential for the initial management of primary anterior traumatic shoulder instability. A generally applicable algorithm for further management is not yet established. The treatment should therefore be individually planned based on patient-specific characteristics.

Transfer RNA genes: landmarks for integration of mobile genetic elements in Dictyostelium discoideum.

In prokaryotes and eukaryotes mobile genetic elements frequently disrupt the highly conservative structures of chromosomes, which are responsible for storage of genetic information. The factors determining the site for integration of such elements are still unknown. Transfer RNA (tRNA) genes are associated in a highly significant manner with different putative mobile genetic elements in the cellular slime mold Dictyostelium discoideum. These results suggest that tRNA genes in D. discoideum, and probably tRNA genes generally in lower eukaryotes, may function as genomic landmarks for the integration of different transposable elements in a strictly position-specific manner.

The effect of multimorbidity on changes in health-related quality of life following hip and knee arthroplasty.

Aims: The aim of this study was to assess the effect of multimorbidity on improvements in health-related quality of life (HRQoL) following total hip arthroplasty (THA) and total knee arthroplasty (TKA). Patients and Methods: Using data from a regional joint registry for 14 573 patients, HRQoL was measured prior and one year following surgery using the Oxford Hip Score (OHS) and Oxford Knee Score (OKS), and the 12-Item Short-Form Health Survey Physical and Mental Component Summary scores (PCS and MCS, respectively). Multimorbidity was defined as the concurrence of two or more self-reported chronic conditions. A linear mixed-effects model was used to test the effects of multimorbidity and the number of chronic conditions on improvements in HRQoL. Results: Almost two-thirds of patients had multimorbidity, which adversely effected improvements in HRQoL. For THA, mean improvements in HRQoL scores were reduced by 2.21 points in OHS, 1.62 in PCS, and 4.14 in MCS; for TKA, the mean improvements were reduced by 1.71 points in OKS, 1.92 in PCS, and 3.55 in MCS (all p < 0.0001). An increase in the number of chronic conditions was associated with increasing reductions in HRQoL improvements. Conclusion: Multimorbidity adversely effects improvements in HRQoL following THA and TKA. Our findings are relevant to healthcare providers focused on the management of patients with chronic conditions and for administrators reporting and monitoring the outcomes of THA and TKA. Cite this article: Bone Joint J 2018;100-B:1168-74.

The assessment of the stability of the tibial component of a novel knee arthroplasty system using radiostereometric analysis.

AIMS: The introduction of a novel design of total knee arthroplasty (TKA) must achieve outcomes at least as good as existing designs. A novel design of TKA with a reducing radius of the femoral component and a modified cam-post articulation has been released and requires assessment of the fixation to bone. Radiostereometric analysis (RSA) of the components within the first two postoperative years has been shown to be predictive of medium- to long-term fixation. The aim of this study was to assess the stability of the tibial component of this system during this period of time using RSA. PATIENTS AND METHODS: A cohort of 30 patients underwent primary, cemented TKA using the novel posterior stabilized fixed-bearing (ATTUNE) design. There was an even distribution of men and women (15:15). The mean age of the patients was 64 years (sd 8) at the time of surgery; their mean body mass index (BMI) was 35.4 kg/m 2 (sd 7.9). RSA was used to assess the stability of the tibial component at 6, 12, and 24 months compared with a six-week baseline examination. Patient-reported outcome measures were also assessed. RESULTS: The mean maximum total point motion (MTPM) of the tibial component between 12 and 24 months postoperatively was 0.08 mm (sd 0.08), which is well below the published threshold of 0.2 mm (p < 0.001). Patient-reported outcome measures consistently improved. CONCLUSION: The tibial component of this novel design of TKA showed stability between assessment 12 and 24 months postoperatively, suggesting an acceptably low risk of medium- to long-term failure due to aseptic loosening.

Assessing the comparability of hip arthroplasty registries in order to improve the recording and monitoring of outcome.

AIMS: We aimed to assess the comparability of data in joint replacement registries and identify ways of improving the comparisons between registries and the overall monitoring of joint replacement surgery. MATERIALS AND METHODS: We conducted a review of registries that are full members of the International Society of Arthroplasty Registries with publicly available annual reports in English. Of the six registries which were included, we compared the reporting of: mean age, definitions for revision and re-operation, reasons for revision, the approach to analysing revisions, and patient-reported outcome measures (PROMs) for primary and revision total hip arthroplasty (THA) and hip resurfacing arthroplasty (HRA). RESULTS: Outcomes were infrequently reported for HRA compared with THA and all hip arthroplasties. Revisions were consistently defined, though re-operation was defined by one registry. Implant survival was most commonly reported as the cumulative incidence of revision using Kaplan-Meier survival analysis. Three registries reported patient reported outcome measures. CONCLUSION: More consistency in the reporting of outcomes for specific types of procedures is needed to improve the interpretation of joint registry data and accurately monitor safety trends. As collecting additional details of surgical and patient-reported outcomes becomes increasingly important, the experience of established registries will be valuable in establishing consistency among registries while maintaining the quality of data. TAKE HOME MESSAGE: As the volume of joint replacements performed each year continues to increase, greater consistency in the reporting of surgical and patient-reported outcomes among joint replacement registries would improve the interpretation and comparability of these data to monitor outcomes accurately.

Measurements of the neutron spectrum in transit to Mars on the Mars Science Laboratory.

The Mars Science Laboratory spacecraft, containing the Curiosity rover, was launched to Mars on 26 November 2011. Although designed for measuring the radiation on the surface of Mars, the Radiation Assessment Detector (RAD) measured the radiation environment inside the spacecraft during most of the 253-day, 560-million-kilometer cruise to Mars. An important factor for determining the biological impact of the radiation environment inside the spacecraft is the specific contribution of neutrons with their high biological effectiveness. We apply an inversion method (based on a maximum-likelihood estimation) to calculate the neutron and gamma spectra from the RAD neutral particle measurements. The measured neutron spectrum (12-436 MeV) translates into a radiation dose rate of 3.8±1.2 µGy/day and a dose equivalent of 19±5 µSv/day. Extrapolating the measured spectrum (0.1-1000 MeV), we find that the total neutron-induced dose rate is 6±2 µGy/day and the dose equivalent rate is 30±10 µSv/day. For a 360 day round-trip from Earth to Mars with comparable shielding, this translates into a neutron induced dose equivalent of about 11±4 mSv.

A family of non-allelic tRNA(ValGUU) genes from the cellular slime mold Dictyostelium discoideum.

A haploid genome of the cellular slime mold Dictyostelium discoideum contains at least 14 non-allelic gene copies coding for a tRNA(ValGUU). The structure, genomic organization, and expression of these genes have been analyzed in relation to stages of the developmental cycle. So far, 13 tRNA(ValGUU) genes have been isolated and characterized. All genes contain identical mature tRNA-coding regions, and consequently identical gene internal promoter elements. However, different genes differ with respect to their 5'- and 3'-flanking regions, although a certain degree of sequence conservation seems apparent. Different members of this tRNA gene family appear to be randomly dispersed along the seven D. discoideum chromosomes, and not clustered at any one genomic location. In vivo expression of individual genes was studied in yeast. All but one tRNA(ValGUU) gene are actively transcribed, though with different efficiencies. There is also evidence that not all of these tRNA genes are constitutively transcribed in Dictyostelium throughout the developmental cycle. One characteristic primary transcript can only be detected in cells of the late preaggregation phase, whereas growing cells, cells in the stationary phase or cells harvested 4 h after the onset of development do not seem to carry this transcript. This product seems to be transcribed from a gene of an unusual structure. Although this particular gene has not yet been isolated, it can be predicted from the sequence of the cDNA synthesized from primary transcription products of this putative gene, that it is composed of nt 1-54 of a 3'-truncated tRNA(ValGUU) gene linked to a bona fide tRNA(ValGUU) gene.

The role of cytoplasmic (newly synthesized) dopamine for the spontaneous and electrically evoked release of dopamine and its metabolites from the isolated neurointermediate lobe of the rat pituitary gland in vitro.

Isolated rat NILs were incubated in Krebs-HEPES solution. The release of dopamine and its metabolites (DOPAC, HVA and MOPET) was determined by HPLC with electrochemical detection. The spontaneous release of the sum of metabolites was about 40 times that of dopamine. The spontaneous outflow of dopamine metabolites was unaffected after inhibition of dopamine uptake (by GBR 12921) or after pretreatment with reserpine (5 mg/kg, 12 h before the experiments), but it was reduced by 50% after preincubation with the irreversible DOPA decarboxylase inhibitor, (MFMD, 10 microM, for 10 min). The combination of pretreatment with reserpine and preincubation with MFMD resulted in an 80% inhibition of the spontaneous outflow of dopamine metabolites. Treatment with reserpine caused a 98% depletion of the dopamine tissue content, whereas 60 min after exposure to MFMD the dopamine tissue content was decreased by 40%. Electrical stimulation of the pituitary stalk (3-15 Hz, in the presence of GBR 12921) caused a frequency-dependent release of dopamine. Stimulation at 7 or 15 Hz caused also a significant release of dopamine metabolites. After pretreatment with reserpine, the release of dopamine evoked by stimulation at 15 Hz was abolished, whereas the evoked release of the metabolites was only reduced by about 55%. After MFMD, the evoked release of dopamine decreased by a percentage similar to that of dopamine tissue content, but the reduction of the evoked release of metabolites was more pronounced. In conclusion, the spontaneous release of dopamine metabolites from the dopaminergic nerve endings in the NIL largely reflects the catabolism of newly synthesized dopamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Endogenous opioids inhibit the in vitro release of endogenous dopamine preferentially in the neural lobe of the rat neurointermediate lobe.

The release of endogenous dopamine (DA) from the in vitro incubated combined neurointermediate lobe (NIL) or isolated neural lobe (NL) was studied. In the presence of the DA uptake inhibitor GBR 12921 (200 nM), electrical stimulation of the pituitary stalk caused an increase of the outflow of DA from the NIL in a frequency-dependent manner. Naloxone (1 microM) enhanced the DA release from the NIL evoked by electrical stimulation at 7 or 15 Hz by about 40%, but had no effect on DA release evoked by stimulation at 3 Hz. When the electrical stimulation was carried out at 15 Hz, the evoked DA release (expressed as fraction of the DA tissue content) from the NL amounted to only 15% of that from the combined NIL. Naloxone (1 microM) increased the evoked DA release from the isolated NL by 242%. Thus, the effect of naloxone on DA release from the combined NIL may be confined mainly to the NL. In conclusion, DA release from the NL is under inhibitory control of endogenous opioids released from the NL during stimulation at 7 or 15 Hz. Beta-Endorphin, known to be released spontaneously at a high rate from in vitro incubated NILs, appears to lack inhibitory effects on DA release from the NIL.

What's new in exogenous osteomyelitis?

By the increase in road and occupational accidents during the past few decades posttraumatic osteomyelitis has become not only the most important type of exogenous but of all inflammatory bone processes. The major morphologic, bacteriologic and immunologic studies about posttraumatic bone inflammation will be outlined in this survey. The histologic classification of chronic osteomyelitis has proved useful for the observation of the course and for the selection of the treatment in 1,500 patients. Detailed morphological studies have shown that posttraumatic osteomyelitis often begins with a necrosis of the outer tangential lamella of the tubular bone partly promoted by partial periosteal retrogression, possibly followed by a necrosis of the fracture ends caused by a disturbance of the medullary blood circulation. Type and extent of osteomyelitis are determined by several traumatic, therapeutic and endogenous factors. Bacteriologically an infection with staphylococcus aureus is still prevailing. Comparative studies about the causative agents shortly after the trauma and during the following osteomyelitis have basically shown an identical range of causative agents. Immunologic studies with monoclonal antibodies in the actual site of inflammation have on the one hand found a decrease in the number of T-lymphocytes and the T-helper cells and on the other hand an increase in the T-suppressor cells, natural killer cells, macrophages in the osteomyelitic site. The impact of these findings on the therapy of osteomyelitis can presently not be estimated. However, they will become important after immunohistochemical studies of the bone and soft tissue Lager in osteosynthetic material after aseptic bone surgery have been carried out.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative osteological-angiological investigations of non-decalcified bony tissue.

A method of investigation on non-decalcified bony tissue is discussed. This method combines the advantages of micro-angiological procedures with those of osteological investigations. By use of this method, a good assignment of angiological results to the differential interference contrast film is possible. The application is indicated for particular osteomyelitis types that are rich in blood vessels, and for some bone tumours.

[Arteriographic features of rare skin complications of chronic osteomyelitis]. / Arteriographische Charakteristika seltener Hautkomplikationen der chronischen Osteomyelitis.

In the period between 1970 and 1982, 6 carcinomas in scar tissue and 2 pseudocarcinomatous skin papillomatosis were found on the basis of chronic osteomyelitides. Amputation specimens of two carcinomas and one papillomatosis were examined by arteriography. Macroscopically carcinomas in scar tissue showed an unspecific appearance and microscopically a scarefied and partly pathological vascular appearance. Pseudocarcinomatous skin papillomatosis was distinctly hypervascular. Therefore, indications with regard to the localisation of an required exploratory excision can only be obtained from the vascular appearance of papillomatosis but not in case of a scar tissue carcinoma after osteomyelitis. Due to the overall bad blood circulation osteomyelitic scar tissue carcinoma scarcely reacts positively to a chemotherapeutic treatment.

[Studies on the angioarchitecture of polypoid colonic processes]. / Untersuchungen zur Angioarchitektur polypöser Kolonprozesse.

Portions of the colon removed at operation were studied angiographically after arterial or venous injection with a barium-gelatin mixture. The aims of the investigation were: To study the differences between tumour and inflammatory angiographic appearances and the clinical value of in vivo angiography of the mesenteric arteries. A comparison of the micro-angiographic appearances of benign and malignant polypoid lesions of the colon. Adenomas and carcinomas showed patterns which are easy to distinguish and permit classification in uncertain lesions. Pseudopolyps in Crohn's disease resemble adenomas in the early stages, but later assume features characteristic of tumours.

Pharmacokinetics of the thioether phospholipid analogue BM 41.440 in rats.

BM 41.440 (1-hexadecylmercapto-2-methoxymethyl-rac-glycero-3-phosphocholine) is a cytotoxic thioether phospholipid analogue that recently has entered phase I trials in cancer patients. The objective of this study was to evaluate the pharmacokinetics of this compound in female rats after administration of a single oral dose (15 mg/kg body weight [bw] ). Furthermore, BM 41.440 serum concentrations were determined under a daily oral treatment of up to 13 weeks. Blood samples were obtained via permanent catheters from the femoral arteries before and after drug administration for a total of 120 hr. Urine was collected in 24 hr-intervals for 120 hr; the volume was measured, and aliquots were stored at -20 C until analytical determination of the thioether derivative. BM 41.440 was assayed in serum and urine by means of a specific, newly developed reverse-phase high pressure liquid chromatography technique. Mean maximum serum concentrations (1.7 micrograms/ml, n = 4 animals) were attained after seven hr. A terminal half-life of ca. 27 hr was calculated from the rate constant for the terminal elimination phase (lambda z approximately 0.026/hr). The mean serum BM 41.440 concentration-time-area-under-the-curve was 52.9 mg X hr/l. The ratio of total body clearance to absorption fraction was 4.7 ml/min X kg bw. Only a small amount of the drug was found in the urine. The quantity excreted in the urine during a 24 hr-interval never exceeded 1.5% of the administered dose.(ABSTRACT TRUNCATED AT 250 WORDS)

[Structural principles of hemostatic processes]. / Strukturierende prinzipien hämostatischer prozesse.

The formation of the hemostatic plug on areas of skin injury is characterized as a sequence of structure-forming processes ending in the formation of an impenetrable barrier. The morphology of this barrier is further elucidated by means of scanning- and transmission electron microscopy. Especially the fibrin coating of the injury shows a completely different formation than is deducible from the solely hemostaseologically orientated view of the formation of the hemostatic plug. These structure-forming processes are: activation of the intrinsic clotting system by means of explosion-like destruction of thrombocytes with an immediate formation of a fibrin clot within seconds after the injury. Later during the process the fibrin clot is then condensed and as a function of thrombocyte dependent retraction receives its final fibrin stabilisation and modellation towards an occluding plug. The very narrow net formation of fibrin fibers is interpreted as dependent on the destruction of thrombocyte pseudopodia using their round shape as a rail for fibrin fiber formation. Disturbances of clot formation of postmortal clots compared to vital clots are interpreted as functional thrombocytic distortions, especially of the thrombocytic energy metabolism. Extracorporal clotting of blood drops after extreme ischemia resemble fibrin structures and fibrin structure formation distortions of postmortal origin.

[Ultrastructure of intravital, postmortem and autolysed fibrin]. / Zur Ultrastruktur vitaler, postmortaler und autolysierter Gerinnsel.

Investigations on animal experimental and human tissue material (skin, musculature, liver) with the scanning electron microscope are reported. These studies were carried out to clarify open questions on extravascular fibrin structures after blunt and sharp traumatization of vital and postmortem nature. The network formation which was already characterized earlier as typically vital and the irregular structure of postmortem coagula could be demonstrated even with modification of the traumatization, especially in tissue hematomas. Experimental investigations on autolysis revealed an exceedingly good preservation of the structure of vital coagulum material with massive damage and granular decomposition of fibrin fiber structures produced postmortem. The structural differences in the mode of interlinking of the fibrin was shown up especially clearly by the autolysis, which suggests an application as preparation technique for the question specified. Special modifications of the preparation technique (fixation according to Karnovsky, critical-point drying) did not provide such substantial advantages for routine investigations that they might be generally recommended.