Relationship of Hip and Trunk Muscle Function with Single Leg Step-Down Performance: Implications for Return to Play Screening and Rehabilitation

ObjectivesEvaluate the relationship of hip and trunk muscle function with the Single Leg Step-Down test (SLSD).Study designLaboratory study.SettingBiomechanics Laboratory.Participants71 healthy participants with no history of anterior cruciate ligament (ACL) or lower extremity injury in the last 3 months completed this study (38 males, 33 females; mean 25.49 ± 0.62 years).Main outcomesHip abduction (HABD), external rotation (HER), and extension (HEXT) peak isometric force were measured. Trunk endurance was measured with plank (PL) and side plank (SPL) tests. SLSD repetitions in 60-s and dynamic knee valgus (VAL) were recorded.ResultsPL, SPL, HABD, HER, and HEXT were positively correlated with SLSD repetitions. PL (r = 0.598, p < 0.001) was most correlated with SLSD repetitions, and regression demonstrated that PL (p = 0.001, R² = 0.469) was a predictor of SLSD repetitions. VAL trended toward negative correlation with PL and SPL. Sex-specific differences were present, with PL, SPL, HABD, and HER showing stronger relationships with SLSD in females.ConclusionHip and trunk muscle function were positively correlated with SLSD performance, and these relationships were strongest in females. PL predicted performance on the SLSD. Further research is needed to investigate the utility of SLSD as a screening or return-to-play test for lower extremity conditions such as ACL injury and patellofemoral pain.     

Top–down signal transmission and global hyperconnectivity in auditory‐visual synesthesia: Evidence from a functional EEG resting‐state study

Auditory‐visual (AV) synesthesia is a rare phenomenon in which an auditory stimulus induces a “concurrent” color sensation. Current neurophysiological models of synesthesia mainly hypothesize “hyperconnected” and “hyperactivated” brains, but differ in the directionality of signal transmission. The two‐stage model proposes bottom–up signal transmission from inducer‐ to concurrent‐ to higher‐order brain areas, whereas the disinhibited feedback model postulates top–down signal transmission from inducer‐ to higher‐order‐ to concurrent brain areas. To test the different models of synesthesia, we estimated local current density, directed and undirected connectivity patterns in the intracranial space during 2 min of resting‐state (RS) EEG in 11 AV synesthetes and 11 nonsynesthetes. AV synesthetes demonstrated increased parietal theta, alpha, and lower beta current density compared to nonsynesthetes. Furthermore, AV synesthetes were characterized by increased top–down signal transmission from the superior parietal lobe to the left color processing area V4 in the upper beta frequency band. Analyses of undirected connectivity revealed a global, synesthesia‐specific hyperconnectivity in the alpha frequency band. The involvement of the superior parietal lobe even during rest is a strong indicator for its key role in AV synesthesia. By demonstrating top–down signal transmission in AV synesthetes, we provide direct support for the disinhibited feedback model of synesthesia. Finally, we suggest that synesthesia is a consequence of global hyperconnectivity. Hum Brain Mapp 39:522–531, 2018. © 2017 Wiley Periodicals, Inc.     

Treatment algorithms in Crohn's – Up,down or something else?

Crohn's disease is a chronic, progressive and disabling condition. New therapeutic goals have emerged in Crohn's disease such as the need to look beyond symptoms by achieving mucosal healing that is known to be associated with better outcomes. Anti-TNF (Tumour Necrosis Factor) therapy is the most potent drug class to induce and maintain mucosal healing in Crohn's disease. Recent evidence indicates that the efficacy profile of thiopurines has been overestimated while the increased risk of malignancies (lymphoma, non-melanoma skin cancers, myeloid disorders) has been underestimated. Methotrexate is well-tolerated, but its potential for disease modification is unknown. Achieving mucosal healing in patients with early Crohn's disease might be the best way to change disease course and patients' life. In 2014, anti-TNF treatment should be the first-line therapy in patients with Crohn's disease who suffer from severe and/or complicated disease and in those with poor prognostic factors. In the remaining patients, a rapid step-up approach based on a tight monitoring is recommended.     

Slowing down as an early warning signal for abrupt climate change

In the Earth's history, periods of relatively stable climate have often been interrupted by sharp transitions to a contrasting state. One explanation for such events of abrupt change is that they happened when the earth system reached a critical tipping point. However, this remains hard to prove for events in the remote past, and it is even more difficult to predict if and when we might reach a tipping point for abrupt climate change in the future. Here, we analyze eight ancient abrupt climate shifts and show that they were all preceded by a characteristic slowing down of the fluctuations starting well before the actual shift. Such slowing down, measured as increased autocorrelation, can be mathematically shown to be a hallmark of tipping points. Therefore, our results imply independent empirical evidence for the idea that past abrupt shifts were associated with the passing of critical thresholds. Because the mechanism causing slowing down is fundamentally inherent to tipping points, it follows that our way to detect slowing down might be used as a universal early warning signal for upcoming catastrophic change. Because tipping points in ecosystems and other complex systems are notoriously hard to predict in other ways, this is a promising perspective.     

Critical slowing down suggests that the western Greenland Ice Sheet is close to a tipping point

The Greenland Ice Sheet (GrIS) is a potentially unstable component of the Earth system and may exhibit a critical transition under ongoing global warming. Mass reductions of the GrIS have substantial impacts on global sea level and the speed of the Atlantic Meridional Overturning Circulation, due to the additional freshwater caused by increased meltwater runoff into the northern Atlantic. The stability of the GrIS depends crucially on the positive melt-elevation feedback (MEF), by which melt rates increase as the overall ice sheet height decreases under rising temperatures. Melting rates across Greenland have accelerated nonlinearly in recent decades, and models predict a critical temperature threshold beyond which the current ice sheet state is not maintainable. Here, we investigate long-term melt rate and ice sheet height reconstructions from the central-western GrIS in combination with model simulations to quantify the stability of this part of the GrIS. We reveal significant early-warning signals (EWS) indicating that the central-western GrIS is close to a critical transition. By relating the statistical EWS to underlying physical processes, our results suggest that the MEF plays a dominant role in the observed, ongoing destabilization of the central-western GrIS. Our results suggest substantial further GrIS mass loss in the near future and call for urgent, observation-constrained stability assessments of other parts of the GrIS.

During the last century, the Greenland Ice Sheet (GrIS) has lost mass at an accelerating rate (1, 2). The mass loss is caused by solid ice discharge into the North Atlantic and surface melting due to increasing temperatures. The relative contribution of the latter has increased from 42% before 2005 to 68% between 2009 and 2012, and surface runoff caused 84% of the increase in mass reduction since 2009 (3). The complete melting of the GrIS would cause a global sea level rise of more than 7 m (4, 5). Continued melting of the GrIS has been suggested to potentially lead to a collapse of the Atlantic Meridional Overturning Circulation via increased freshwater flux into the North Atlantic (6, 7), which may, in turn, trigger a cascade of transitions in additional tipping elements such as the Amazon rainforest and the tropical monsoon systems (6, 8–10).In addition to the centennial-scale variability associated with the increasing trend in mean temperatures related to anthropogenic climate change, the pace of mass loss has decadal-scale fluctuations caused by natural variations in external oceanic and atmospheric forcing. The imprints of these natural, decadal-scale fluctuations are spatially heterogeneous across the GrIS. Since the early 2000s, periods of persistently negative phases of the North Atlantic Oscillation (NAO) and a positive phase of the East Atlantic Pattern (11) have led to a weakening and southward shift of the jet stream, and more persistent blocking (12) over Greenland during summer, resulting in overall increased mass reduction rates (2, 13). On the other hand, a slowing down of mass loss since 2013—which inverted again in 2019—was caused by more periods with a persistent positive NAO (14). Moreover, recent observations show that the Jakobshavn glacier has been advancing again since 2016 due to anomalous wintertime heat loss in the boundary current around southern Greenland (15). However, these natural fluctuations do not have a sustained impact on melt rates comparable to the longer-term trend toward overall increasing melt rates caused by anthropogenic global warming (Fig. 1A).Open in a separate windowFig. 1.(A) Summer sea level temperatures from the Ilulissat station in CWG (25) (blue curves) and Arctic temperature anomalies (26) (red curves). The linear trend of the station data (dashed blue curve) corresponds to 1.3 °C warming per century. Arctic temperature anomalies are shown only for comparison; only the station data (blue curves) are used for our analysis. (B) Melt rates from the CWG ice core stack (blue curve) and the NU peninsula core (red curve), given as z scores with respect to a normal distribution (18). (C) Detrended logarithmic CWG (blue curve) and NU (red curve) melt rates. A Gaussian filter with bandwidth σ=30 y was used for detrending. The runoff and melt time series are preprocessed in this way before computing the EWS indicators to exclude potential biases by underlying trends; in particular, we take the logarithm of the melt rates in order to account for skewed data distributions. (D) The variance of the CWG (blue curves) and NU (red curves) melt rates. (E) The AC1 of the CWG (blue curves) and NU (red curves) melt rates. Note that the AC1, despite a significantly positive trend, appears to have at least temporarily stabilized in the last few decades. It should be noted, however, that the AC1 is generally influenced by (multi)decadal variability (27). The window size for computing the variance and the AC1 is w=70 y, and values are plotted at the windows’ endpoints. Data for the first w=70 y are omitted to ensure that all windows contain the same number of data points. The dashed lines in D and E indicate linear trends of the variance and AC1, and P values for positive slopes as determined from a phase surrogate test are indicated in the legend (see Materials and Methods). The statistical significance of the positive trends is robust across wide ranges of the bandwidth σ and the sliding window size (SI Appendix, Fig. S1).Early model simulations suggest that melting of the GrIS is inevitable beyond a critical global mean temperature threshold of 0.8 °C to 3.2 °C above preindustrial levels, with a best estimate of 1.6 °C (16). More recent comprehensive modeling results show that, for the representative concentration pathway 8.5 (RCP8.5), the GrIS melts entirely until AD 3000 (5). Arctic temperatures have increased more than the global average (17) (Fig. 1A), and the nonlinear increase in GrIS melt rates and runoff that have recently been detected (18) (Fig. 1B) suggests that the critical temperature threshold may be closer than previously thought. We emphasize that the surface mass balance turning negative is not a necessary condition for stability loss, and the temperature may reach a critical threshold years before a turning point in the mass balance (16).Idealized models of critical transitions in natural systems suggest that the loss of stability of an equilibrium (fixed point) is observable before the abrupt transition (19). In dynamical systems with random forcing, one can show that, if a system approaches a bifurcation where an equilibrium point loses its stability, the variance of the fluctuations around the equilibrium will increase, as will the characteristic decay time of the autocorrelation function of these fluctuations. The change in dynamics that occurs as stability is lost is often called critical slowing down, and the associated statistical precursor signs in terms of rising variance and lag-one autocorrelation (AC1) are called early-warning signals (EWS) (19). Such statistical EWS associated with critical slowing down are, for example, detectable in the temperature proxy from the North Greenland Ice Core Project before several of the Dansgaard–Oeschger events of the last glacial interval (20, 21), as well as before other abrupt transitions in past climates (22). In the context of anthropogenic global warming, EWS are expected to precede potential abrupt transitions in the Earth system’s major tipping elements, such as the polar ice sheets, the Atlantic Meridional Overturning Circulation, or the tropical monsoon systems (23). We investigate here a possible tipping point for the GrIS based on the theory of critical slowing down.In the following, we will first show that central-western Greenland (CWG) melt rates exhibit robust and significant EWS. We then reconstruct the corresponding CWG ice sheet height changes and show that they can be captured well by a simple model focusing on the melt elevation feedback (MEF). We then demonstrate that pronounced EWS can also be found in the fluctuations of the reconstructed ice sheet height around the equilibrium of the model and show that these EWS are consistent with the theoretical expectations provided by the MEF model.     

Step‐down approach using either cyclosporin A or methotrexate as maintenance therapy in early rheumatoid arthritis

Objective

To evaluate the feasibility and outcome of the step‐down approach using either cyclosporin A (CSA) or methotrexate (MTX) as maintenance therapy following 6 months treatment with these 2 agents in combination in early, nonerosive rheumatoid arthritis (RA).

Methods

Fifty‐seven patients younger than 65 years with early, nonerosive RA were first treated with CSA and MTX in combination for 6 months. They were then randomly stepped down to single‐agent maintenance treatment for another 18 months. Safety, clinical efficacy, survival on treatment, and radiographic progression were evaluated.

Results

When being treated with combination therapy, 7 of the 57 patients (12.3%) withdrew because of adverse events. Of the remaining 50 patients, 42 (84.0%) were American College of Rheumatology (ACR) 20% responders, 30 (60.0%) were ACR 50% responders, and 23 (46.0%) were ACR 70% responders. At month 6, 22 patients were randomized to CSA and 27 to MTX. During this trial period, the treatment was discontinued by 16 patients taking CSA (mainly because of loss of efficacy) and by 4 taking MTX. At month 24, the probability (± SEM) of survival on treatment was 0.273 ± 0.09 for CSA and 0.852 ± 0.07 for MTX. Of the 6 CSA patients who completed the trial, 4 (66.7%) were ACR 20% responders, and 3 (50%) were both ACR 50% and ACR 70% responders. Of the 23 completers in the MTX arm, 21 (91.3%) were ACR 20% responders, 18 (78.3%) were ACR 50%, and 10 (43.5%) were ACR 70% responders. The treatment was not responsible for severe adverse events. Radiography showed a slow progression in the damage score and number of eroded joints in both treatment groups.

Conclusion

Stepping down to single agent maintenance therapy following 6 months of combination treatment with CSA and MTX in early RA was only successful with MTX. Because this treatment did not prevent some radiographic progression, other approaches (e.g., step‐up approach) may be more appropriate in early RA.

     

Unusual cause of lung and renal disease in a baby with trisomy 21

We describe a case of right thoracic ectopic kidney in a 13-month-old boy with trisomy 21. We think an intrathoracic kidney should be considered in the differential diagnosis of a thoracic mass.     

Attentional capture during visual search is attenuated by target predictability: Evidence from the N2pc,Pd, and topographic segmentation

Attentional capture by salient distractors has been confirmed by the occurrence of an N2pc to the salient distractor. To clarify some failures to replicate this finding, we varied target predictability to induce different search modes. In the unpredictable target condition, the target shape varied randomly from trial to trial, favoring singleton detection mode. In the predictable target condition, the target shape remained the same in a block of trials, favoring feature search mode. With unpredictable targets, we observed an N2pc toward the salient color distractor, confirming attentional capture in singleton search mode. With predictable targets, there was no N2pc to the salient distractor, but a distractor positivity (Pd), suggesting distractor suppression. Also, differences emerged in the topographic segmentation of N2pc and Pd. Further, the amplitude of the N2pc toward the target was larger with predictable than with unpredictable targets.