To describe CSF biomarker profiles in posterior cortical atrophy (PCA), which induces high-order visual deficits often associated with Alzheimer disease (AD) pathology, and relate these findings to ...clinical and neuropsychological assessment.
This prospective observational study included 22 patients with PCA who underwent CSF biomarker analysis of total tau (t-tau), phosphorylated tau on amino acid 181 (p-tau181), and amyloid β (Aβ(42)). At group level, the CSF profiles of patients with PCA were compared to those of patients with typical AD and patients with other dementia (OD). Individually, the clinical presentation of patients with PCA was correlated to their CSF profile to assess the predictability of clinical features for diagnosis of underlying AD pathology.
At group level, the PCA biomarker profile was not different from that of the AD group, but very different from that of the OD group (p < 0.001). More than 90% of patients with PCA had CSF profiles consistent with AD. All patients with PCA with either isolated higher-order visual deficit (n = 8) or visual deficit associated with memory impairment (n = 11) had CSF profiles consistent with AD. Only one of the 3 patients with PCA with asymmetric motor signs fulfilled biological CSF criteria for AD.
PCA syndrome is usually associated with CSF biomarkers suggestive of AD, as shown by previous neuropathologic studies. This does not apply in case of motor signs suggesting associated corticobasal syndrome. CSF biomarkers help to discriminate AD from non-AD processes associated with this condition.
The observed summertime drying over Northern Central India (NCI) during the latter half of the twentieth century is not reproduced by the Coupled Model Intercomparison Project Phase 5 (CMIP5) model ...ensemble average. At the same time, the spread between precipitation trends from individual model realizations is large, indicating that internal variability potentially plays an important role in explaining the observed trend. Here we show that the drying is indeed related to the observed 1950–1999 positive trend of the Pacific Decadal Oscillation (PDO) index and that the relationship is even stronger for a simpler index (S1). Adjusting the CMIP5‐simulated precipitation trends to account for the difference between the observed and simulated S1 trend increases the original multimodel average NCI drying trend from −0.09 ± 0.31 mm d−1 (50 years)−1 to −0.54 ± 0.40 mm d−1 (50 years)−1. Thus, our estimate of the 1950–1999 NCI drying associated with Pacific decadal variability is of similar magnitude as our previous CMIP5‐based estimate of the drying due to anthropogenic aerosol. The drying (moistening) associated with increasing (decreasing) S1 can partially be attributed to a southeastward (northwestward) shift of the boundary between ascent and descent affecting NCI. This shift of the ascent region strongly affects NCI but not Southeast Asia and south China. The average spread between individual model realizations is only slightly reduced when adjusting for S1 as smaller‐scale variability also plays an important role.
Key Points
Multidecadal variability helps to explain 1950–1999 summertime drying over India
CMIP5 model results reconciled with observations
Drying linked to variability likely to be offset by moistening in the future
Background Isolated varus osteoarthritis of the knee is a common problem in patients engaged in sports and recreational activities.
Hypothesis Patients will be able to resume sporting activity after ...high tibial osteotomy.
Study Design Case series; Level of evidence, 4.
Methods A total of 65 patients were surveyed by postal questionnaires to determine their sporting and recreational activities at
an average of 36 ± 8.1 months (range, 14â84) after high tibial osteotomy for the treatment of medial compartment knee osteoarthritis.
The clinical evaluation included the Lysholm score, the Tegner activity scale, the Activity Rating Scale, and a visual analog
scale for pain.
Results At the time of survey, 90.9% of patients were engaged in sports and recreational activities, compared with 87.9% before surgery
( P = .182). The number of different sporting activities declined from 3.5 preoperatively to 3.0 after surgery ( P = .178). The sports frequency per week (2.1 sessions) and the activity duration per week (4.1 hours) did not significantly
change from preoperative to postoperative (2.3, P = .211; and 4.2 hours, P = .709, respectively). The Lysholm score (42.4) and the visual analog scale (6.9) illustrated significant improvements (69.6,
P = .001; and 2.9, P < .001, respectively). No patient returned to competitive sports after surgery, and declines were noted in the Tegner (4.9
± 2.3 to 4.3 ± 1.5, P < .05) and Activity Rating Scale (5.7 ± 5.2 to 3.3 ± 4.6, P = .001) scores. After surgery, many patients continued to engage in high-level activities such as downhill skiing or mountain
biking.
Conclusion High tibial osteotomy for the treatment of medial compartment knee osteoarthritis in the active patient demonstrated favorable
clinical results and allowed patients to return to sports and recreational activities similar to the preoperative level.
A new stratiform cloud scheme including a two-moment bulk microphysics module, a cloud cover parameterization allowing ice supersaturation, and an ice nucleation parameterization has been implemented ...into the recently developed GFDL AM3 general circulation model (GCM) as part of an effort to treat aerosol-cloud-radiation interactions more realistically. Unlike the original scheme, the new scheme facilitates the study of cloud-ice-aerosol interactions via influences of dust and sulfate on ice nucleation. While liquid and cloud ice water path associated with stratiform clouds are similar for the new and the original scheme, column integrated droplet numbers and global frequency distributions (PDFs) of droplet effective radii differ significantly. This difference is in part due to a difference in the implementation of the Wegener-Bergeron-Findeisen (WBF) mechanism, which leads to a larger contribution from super-cooled droplets in the original scheme. Clouds are more likely to be either completely glaciated or liquid due to the WBF mechanism in the new scheme. Super-saturations over ice simulated with the new scheme are in qualitative agreement with observations, and PDFs of ice numbers and effective radii appear reasonable in the light of observations. Especially, the temperature dependence of ice numbers qualitatively agrees with in-situ observations. The global average long-wave cloud forcing decreases in comparison to the original scheme as expected when super-saturation over ice is allowed. Anthropogenic aerosols lead to a larger decrease in short-wave absorption (SWABS) in the new model setup, but outgoing long-wave radiation (OLR) decreases as well, so that the net effect of including anthropogenic aerosols on the net radiation at the top of the atmosphere (netradTOA = SWABS-OLR) is of similar magnitude for the new and the original scheme.
The pattern of lateral meniscus tears observed in anterior cruciate ligament (ACL)-injured subjects varies greatly and determines subsequent management. Certain tear patterns with major biomechanical ...consequences should be repaired in a timely manner. Knowledge about risk factors for such tears may help to identify patients in the early posttraumatic phase and subsequently may improve clinical results.
A database of 268 patients undergoing primary ACL reconstruction was used to identify all patients with isolated ACL tears and patients with an associated tear of the lateral meniscus. Patients who underwent surgery >6 months after the injury were excluded. Based on the arthroscopic appearance of the lateral meniscus, patients were assorted to one of three groups: 'no tear,' 'minor tear,' and 'major tear.' Tear patterns defined as major included root tears, complete radial tears, and unstable longitudinal tears including bucket-handle tears. Univariate analysis was performed by comparing the three groups with regard to gender, age, height, weight, BMI, type of injury (high-impact sport, low-impact sport, and not sports related), and mechanism of injury (non-contact vs. contact). Multivariate logistic regression was carried out to identify independent risk factors for minor and major meniscal tears and to calculate odds ratios (OR).
Two hundred fifteen patients met the inclusion and exclusion criteria. Of those, 56% had isolated ACL tears, 27% had associated minor tears, and 17% had associated major tears of the lateral meniscus. Univariate analysis revealed significant differences between the three groups for gender (p = 0.002), age groups (p = 0.026), and mechanism of injury (p < 0.001). A contact injury mechanism was a risk factor for minor tears (OR: 4.28) and major tears (OR: 18.49). Additional risk factors for major tears were male gender (OR: 7.38) and age <30 years (OR: 5.85).
Male patients, patients <30 years, and particularly patients who sustained a contact injury have a high risk for an associated major lateral meniscus tear. Special attention is therefore necessary in those patients and early referral to magnetic resonance imaging and/or arthroscopy is recommended to allow meniscus repair in a timely manner.
In patients with osteoarthritis (OA), intraarticular injection of hyaluronic acid (HA) frequently results in reduced pain and improved function for prolonged periods of time, i.e. more than 6 months. ...However, the mechanisms underlying these effects are not fully understood. Our underlying hypothesis is that HA modifies the enzymatic breakdown of joint tissues.
To test this hypothesis, we examined osteochondral cylinders from 12 OA patients. In a bioreactor, these samples were stimulated by interleukin 1β (Il1ß) (2 ng/ml) plus mechanical load (2.0 Mpa at 0.5 Hz horizontal and 0.1 Hz vertical rotation), thus the experimental setup recapitulated both catabolic and anabolic clues of the OA joint.
Upon addition of HA at either 1 or 3 mg/ml, we observed a significant suppression of expression of metalloproteinase (MMP)-13. A more detailed analysis based on the Kellgren and Lawrence (K&L) OA grade, showed a much greater degree of suppression of MMP-13 expression in grade IV as compared to grade II OA. In contrast to the observed MMP-13 suppression, treatment with HA resulted in a suppression of MMP-1 expression only at 1 mg/ml HA, while MMP-2 expression was not significantly affected by either HA concentration.
Together, these data suggest that under concurrent catabolic and anabolic stimulation, HA exhibits a pronounced suppressive effect on MMP-13. In the long-run these findings may benefit the development of treatment strategies aimed at blocking tissue degradation in OA patients.
The current gold standard to treat large cartilage defects is autologous chondrocyte transplantation (ACT). As a new surgical method of cartilage regeneration, minced cartilage implantation (MCI) is ...increasingly coming into focus. The aim of this study is to investigate the influence of chondrogenesis between isolated and cultured chondrocytes compared to cartilage chips in a standardized inflammation model with the proinflammatory cytokine TNFα. Articular chondrocytes from bovine cartilage were cultured according to the ACT method to passage 3 and transferred to spheroid culture. At the same time, cartilage was fragmented (<1 mm
) to produce cartilage chips. TNFα (20 ng/mL) was supplemented to simulate an inflammatory process. TNFα had a stronger influence on the passaged chondrocytes compared to the non-passaged ones, affecting gene expression profiles differently between isolated chondrocytes and cartilage chips. MCI showed less susceptibility to TNFα, with reduced IL-6 release and less impact on inflammation markers. Biochemical and histological analyses supported these findings, showing a greater negative influence of TNFα on the passaged pellet cultures compared to the unpassaged cells and MCI constructs. This study demonstrated the negative influence of TNFα on chondrogenesis in a chondrocyte spheroid culture and cartilage fragment model. Passaged chondrocytes are more sensitive to cytokine influences compared to non-passaged cells and chondrons. This suggests that MCI may have superior regeneration potential in osteoarthritic conditions compared to ACT. Further investigations are necessary for the translation of these findings into clinical practice.
Motion capture analysis (MCA) has the advantage of providing a static and dynamic leg axis analysis without radiation. Nevertheless, there is a lack of evidence regarding the accuracy of this ...technique. To test whether mechanical femorotibial axis angle (MAA) measurement recorded with a non-invasive MCA system is equal to the gold standard static long-standing full-leg radiographs (LSX) and if the degree of malalignment or other parameters (BMI, body mass, height, age) influence the accuracy, a total of 102 consecutive patients were examined using LSX and MCA. Static as well as all gait motion phases at 3 km/h were analyzed regarding the difference between the two angles. There was no statistical difference for MAA between LSX (MAArad) and MCA (MAAstat) (p = 0.091). There was a strong correlation (rs = 0.858, p < 0.001) between the two methods. The highest accuracy was detected for values of standing MCA. Also, the gait MCA values showed strong correlation with LSX but weaker correlation compared to standing MCA (initial swing rs = 0.549; terminal stance rs = 0.815; p < 0.001). BMI, body mass, and height did not influence the accuracy of MCA. MCA enables frontal alignment analysis with high accuracy and without the side effect of radiation.
In the past few years, autologous chondrocyte implantation has been shown to be the most suitable cartilage reconstructive technique with the best tissue quality. Although this method is part of the ...standard surgical repertoire in the knee joint, it has so far not been an established method in the ankle because there are no prospective randomized controlled studies to prove a significant advantage over alternative methods of cartilage repair. The methods most frequently used in this context (e.g., marrow stimulation techniques) can, however, at most generate hyaline-like and thus biomechanically inferior regenerates. Minced cartilage implantation, on the other hand, is a relatively simple and cost-effective 1-step procedure with promising biological potential and—at least in the knee joint—satisfactory clinical results. We present an arthroscopic surgical technique by which the surgeon can apply autologous chondrocytes in a 1-step procedure (AutoCart; Arthrex, Munich, Germany) to treat articular cartilage defects in the ankle joint.
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The Hamburg Aerosol Module version 2.3 (HAM2.3) from the ECHAM6.3‐HAM2.3 global atmosphere‐aerosol model is coupled to the recently developed icosahedral nonhydrostatic ICON‐A (icon‐aes‐1.3.00) ...global atmosphere model to yield the new ICON‐A‐HAM2.3 atmosphere‐aerosol model. The ICON‐A and ECHAM6.3 host models use different dynamical cores, parameterizations of vertical mixing due to sub‐grid scale turbulence, and parameter settings for radiation balance tuning. Here, we study the role of the different host models for simulated aerosol optical thickness (AOT) and evaluate impacts of using HAM2.3 and the ECHAM6‐HAM2.3 two‐moment cloud microphysics scheme on several meteorological variables. Sensitivity runs show that a positive AOT bias over the subtropical oceans is remedied in ICON‐A‐HAM2.3 because of a different default setting of a parameter in the moist convection parameterization of the host models. The global mean AOT is biased low compared to MODIS satellite instrument retrievals in ICON‐A‐HAM2.3 and ECHAM6.3‐HAM2.3, but the bias is larger in ICON‐A‐HAM2.3 because negative AOT biases over the Amazon, the African rain forest, and the northern Indian Ocean are no longer compensated by high biases over the sub‐tropical oceans. ICON‐A‐HAM2.3 shows a moderate improvement with respect to AOT observations at AERONET sites. A multivariable bias score combining biases of several meteorological variables into a single number is larger in ICON‐A‐HAM2.3 compared to standard ICON‐A and standard ECHAM6.3. In the tropics, this multivariable bias is of similar magnitude in ICON‐A‐HAM2.3 and in ECHAM6.3‐HAM2.3. In the extra‐tropics, a smaller multivariable bias is found for ICON‐A‐HAM2.3 than for ECHAM6.3‐HAM2.3.
Plain Language Summary
Aerosols are tiny particles in the air which are either emitted into the atmosphere directly or formed from precursor gases such as sulfur dioxide. Aerosols reflect and absorb solar radiation and affect the radiative properties of clouds. In order to estimate how changing emissions of aerosol precursor gases and aerosols affect the radiation budget of the atmosphere, aerosol models are coupled to global atmosphere models. Here, an aerosol model that has already been part of a well‐established coupled model is coupled to a recently developed atmosphere model. The reasons for differences between the original and the new model are investigated and simulated aerosol optical thickness is evaluated against observations. The aerosol optical thickness over subtropical oceans is lower in the new model, which is in better agreement with estimates from satellite observations. This better agreement is traced back to a parameter setting in the cloud description part in the new model. However, because cancellation of positive and negative biases is reduced in the new model, the global mean aerosol optical thickness is biased lower the new model. A bias score based on several meteorological variables is lower in the new model because of lower biases in the extra‐tropics.
Key Points
The new ICON‐A‐Hamburg Aerosol Module version 2.3 (HAM2.3) global atmosphere‐aerosol model is introduced
The sensitivity of simulated aerosol optical thickness (AOT) to using two different host models but the same aerosol module is investigated
A positive AOT bias over subtropical oceans is remedied in ICON‐A‐HAM2.3 because of a different parameter setting in the host model
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