Transitions between symmetrical and asymmetrical gaits: a biomechanical analysis

INTRODUCTION: Gallop is a skipping gait in which one leg (the leading leg) is continuously kept in front of the other (3). This type of locomotion occurs spontaneously in the development of locomotion in children (1) and occurs sometimes in adults when descending stairs or a slope at high speed (2). Although gallop is a naturally occurring human locomotion pattern, research on human gallop is limited. METHODS: Fifteen female subjects with homogeneous stature were selected. They were asked to walk, run and gallop at preferred speed and to perform multiple transitions from walking to running (WRT), galloping to running (GRT) and walking to galloping (WGT). Subjects were equipped with 59 reflective markers and performed the trials on an overground walkway with 6 built‐in forceplates and 12 infrared cameras (Pro Reflex, Qualisys). Kinematics and kinetics were calculated using commercial software (Visual 3D, C‐motion). RESULTS: Subjects consistently used the same leading leg during gallop. Joint kinematics and kinetics showed differences between the leading and trailing leg in gallop. Transition speed of GRT (3.83±0.34ms‐1) was significantly higher than transition speed of WGT (2.66±0.24ms‐1)(p<0.01) and WRT (2.82±0.26ms‐1)(p<0.01) but no statistical difference was found between WGT and WRT (p=0.410)(fig.1). A clear transition step was seen in the WRT and the GRT based on joint kinematics, kinetics, and patterns of mechanical energy. In the WRT, GRT and WGT the swing phase prior to the transition step showed greater (dorsi)flexion in the ankle, knee and hip in comparison with previous walking/galloping steps. In the WGT (2.66±0.24 ms‐1) also the stance phase in the step before transition showed more (dorsi)flexion in the ankle, knee and hip. When subjects initiated the WGT when the leading leg was not in front, they showed some inconsistent intermediate running/skipping steps before they started galloping. Fig.1: transition speed for WGT, WRT and GRT. *and* are significant differences between transitions (p<0,01) CONCLUSIONS: Gallop is appropriately called an asymmetrical gait pattern as the leading and trailing leg execute a different movement. Adults seldom switch spontaneously from walking to galloping so the WGT is supposed to be planned. Still the initiation of transition seems to occur spontaneously because transition sometimes initiated when the leading leg was not in front. If the transition would occur intentionally, one would expect that transition only initiates when the leading leg is in front. Transition speed is very similar for WGT and WRT so it could be that a similar mechanism (arising in the acceleration from walking) determines when the transition occurs. Transition is prepared in the same way in the WRT and the GRT. There is a limited preparation in the swing phase preceding the actual transition step. In the WGT two transition steps were seen. As both legs carry out a different movement in gallop, it seems like each leg needs a transition step to alter the new gait configuration. The transition from an asymmetrical gait pattern to a symmetrical gait pattern (GRT) seems easier to perform than a transition from a symmetrical gait pattern to an asymmetrical gait pattern (WGT) as at least two steps were necessary to make the transition in the WGT in comparison with one step in the GRT. The gait pattern before the transitions, seems to determine the instant of transition initiation (similarity between WGT and WRT). The gait pattern after transition seems to be important in the way the transition is prepared (similarity between WRT and GRT). REFERENCES 1.Clark JE, Whitall J. Changing patterns of locomotion: from walking to skipping. In: Woollacott M, Shumway‐Cook A, editors. Development of posture and gait across the life span. Columbia: University of South Carolina Press; 1989.p. 128‐51. 2.Getchell N, Whitall J. Transitions to and from asymmetrical gait patterns. Journal of Motor Behaviour. 2004; 36 (1):13‐27. 3.Minetti AE. The biomechanics of skipping gaits: a third locomotion paradigm? Proceedings of the Royal Society B: Biological Sciences. 1998;265:1227‐35

Need an expert opinion? Thoughts on the genesis of child psychiatric expertise

From the 1920s, children in Switzerland were psychiatrically examined in observation wards. In many cases, these medical reports were linked to the placement of children in homes and foster families. Focusing on a specific case study of the observation institution Stephansburg in Zurich in 1944, this paper retraces the genesis of a child psychiatric report, identifying patterns by which the experts dealt with narratives of teachers, parents or school doctors. At a closer look, tests and medical examinations were not necessarily committed to a strictly scientific approach. The case study analysed in this paper indicates that experts in child psychiatry did not always apply expert knowledge when preparing their opinion. Rather, they resorted to a selection of aspects alien to psychiatry but suitable to satisfy the interests of the contracting authority.From the 1920s, children in Switzerland were psychiatrically examined in observation wards. In many cases, these medical reports were linked to the placement of children in homes and foster families. Focusing on a specific case study of the observation institution Stephansburg in Zurich in 1944, this paper retraces the genesis of a child psychiatric report, identifying patterns by which the experts dealt with narratives of teachers, parents or school doctors. At a closer look, tests and medical examinations were not necessarily committed to a strictly scientific approach. The case study analysed in this paper indicates that experts in child psychiatry did not always apply expert knowledge when preparing their opinion. Rather, they resorted to a selection of aspects alien to psychiatry but suitable to satisfy the interests of the contracting authority

Observation of an Estuarine Turbidity Maximum in the Highly Impacted Capibaribe Estuary, Brazil

Background: Alterations in insulin-like growth factor I (IGF-I) signaling have been associated with dementia and Alzheimer's disease (AD). Studies on the association between IGF-I levels and dementia risk have been inconclusive. We reported earlier that higher levels of IGF-I receptor stimulating activity are associated with a higher prevalence and incidence of dementia. Objective: In the present study, we test the robustness of the association between IGF-I receptor stimulating activity and dementia by extending the follow-up period to 16 years and investigate possible effect modification by apolipoprotein E (ApoE). Methods: At baseline, circulating IGF-I receptor stimulating activity was determined by the IGF-I kinase receptor activation (KIRA) assay in 1,014 elderly from the Rotterdam Study. Dementia was assessed from baseline (1997-1999) to follow-up in January 2015. Associations of IGF-I receptor stimulating activity and incident dementia were assessed with Cox proportional hazards models. Results: During 10,752 person-years of follow-up, 174 people developed dementia. In the extended follow-up we no longer observed a dose-response relationship between IGF-I receptor stimulating activity and risk of dementia [adjusted odds ratio 1.11; 95% confidence interval (CI) 0.97-1.28]. Interestingly, we found evidence of an interaction between ApoE-ε4 and tertiles of IGF-I receptor stimulating activity. IGF-I receptor stimulating activity in the median and top tertiles was related to increased dementia incidence in hetero- and homozygotes of the ApoE-ε4 allele, but did not show any association with dementia risk in people without the ApoE-ε4 allele (adjusted odds ratio medium vs. low IGF-I receptor stimulating activity in ApoE-ε4 carriers: 1.45; 95% CI 1.00-2.12). These findings suggest a threshold effect in ApoE-ε4 carriers. In line with the hypothesis that downregulation of IGF-I signaling is associated with increased dementia risk, ApoE-ε4 homozygotes without prevalent dementia displayed lower levels of IGF-I receptor stimulating activity than heterozygotes and non-carriers. Conclusion: The findings shed new light on the association between IGF-I signaling and the neuropathology of dementia and ask for replication in other cohorts, using measures of IGF-I receptor stimulating activity rather than total serum levels as putative markers of dementia risk

Proton pump inhibitor use and risk of hepatic encephalopathy : a multicentre study

Background & Aims: Data on the association between proton pump inhibitor (PPI) use and hepatic encephalopathy (HE) are conflicting, and data from multicentre studies are scarce. The aim of this study was to dissect the potential association between PPI use and minimal (MHE) and overt HE (OHE). Methods: Data from patients with cirrhosis recruited at seven centres across Europe and the US were analysed. MHE was defined by the psychometric hepatic encephalopathy score (PHES). PPI use was recorded on the day of testing with PHES. Patients were followed for OHE development and death/liver transplantation. Results: A total of 1,160 patients with a median MELD of 11 were included (Child-Pugh stages: A 49%/B 39%/C 11%). PPI use was noted in 58% of patients. Median follow-up time was 18.1 months, during which 230 (20%) developed an OHE episode, and 224 (19%) reached the composite endpoint of death/liver transplantation. In multivariable analyses, PPI use was neither associated with the presence of MHE at baseline nor OHE development during follow-up. These findings were consistent in subgroup analyses of patients with Child-Pugh A or B cirrhosis and after excluding patients with a history of OHE. PPI use was also not associated with a higher risk of OHE, neither in patients with an indication for treatment nor in patients without an indication. Conclusions: PPI use is not associated with a higher risk of HE in patients with cirrhosis. Based on these findings, at present, a prescription should not be prohibited in case of a generally accepted indication. Impact and implications: Data on the association between proton pump inhibitor (PPI) use and hepatic encephalopathy (HE) are conflicting. In this study, PPI use was not associated with a higher risk of minimal HE at baseline or overt HE during follow-up in patients with cirrhosis. Based on these findings, prescription of a PPI for a generally accepted indication should not be prohibited in patients with cirrhosis

Revisiting the Role of Insulin-Like Growth Factor-I Receptor Stimulating Activity and the Apolipoprotein E in Alzheimer’s Disease

Background: Alterations in insulin-like growth factor I (IGF-I) signaling have been associated with dementia and Alzheimer’s disease (AD). Studies on the association between IGF-I levels and dementia risk have been inconclusive. We reported earlier that higher levels of IGF-I receptor stimulating activity are associated with a higher prevalence and incidence of dementia.Objective: In the present study, we test the robustness of the association between IGF-I receptor stimulating activity and dementia by extending the follow-up period to 16 years and investigate possible effect modification by apolipoprotein E (ApoE).Methods: At baseline, circulating IGF-I receptor stimulating activity was determined by the IGF-I kinase receptor activation (KIRA) assay in 1,014 elderly from the Rotterdam Study. Dementia was assessed from baseline (1997–1999) to follow-up in January 2015. Associations of IGF-I receptor stimulating activity and incident dementia were assessed with Cox proportional hazards models.Results: During 10,752 person-years of follow-up, 174 people developed dementia. In the extended follow-up we no longer observed a dose-response relationship between IGF-I receptor stimulating activity and risk of dementia [adjusted odds ratio 1.11; 95% confidence interval (CI) 0.97–1.28]. Interestingly, we found evidence of an interaction between ApoE-ε4 and tertiles of IGF-I receptor stimulating activity. IGF-I receptor stimulating activity in the median and top tertiles was related to increased dementia incidence in hetero- and homozygotes of the ApoE-ε4 allele, but did not show any association with dementia risk in people without the ApoE-ε4 allele (adjusted odds ratio medium vs. low IGF-I receptor stimulating activity in ApoE-ε4 carriers: 1.45; 95% CI 1.00–2.12). These findings suggest a threshold effect in ApoE-ε4 carriers. In line with the hypothesis that downregulation of IGF-I signaling is associated with increased dementia risk, ApoE-ε4 homozygotes without prevalent dementia displayed lower levels of IGF-I receptor stimulating activity than heterozygotes and non-carriers.Conclusion: The findings shed new light on the association between IGF-I signaling and the neuropathology of dementia and ask for replication in other cohorts, using measures of IGF-I receptor stimulating activity rather than total serum levels as putative markers of dementia risk

Minimal hepatic encephalopathy is associated with a higher risk of overt hepatic encephalopathy and poorer survival

Background and aims Minimal hepatic encephalopathy (MHE) is a frequent complication in patients with liver cirrhosis. Its impact on predicting the development of overt hepatic encephalopathy (OHE) and survival has not been studied in large multicenter studies. Methods Data from patients recruited at eight centers across Europe and the United States were analyzed. MHE was detected using the psychometric hepatic encephalopathy score (PHES). A subset was also tested with the simplified animal naming test (S-ANT1). Patients were followed for OHE development and death/liver transplantation (LTx). Results A total of 1462 patients with a median model of end-stage liver disease of 11 were included (Child-Pugh (CP) stages: A 47%/B 41%/C 12%). Median follow-up time was 19 months, during which 336 (23%) patients developed an OHE episode and 464 (32%) reached the composite end point of death/LTx (369 deaths, 95 LTx). In multivariable analyses, MHE (defined by PHES) was associated with the development of OHE (subdistribution hazard ratio 1.74, p < 0.001) and poorer LTx-free survival (hazard ratio 1.53, p < 0.001) in the total cohort as well as in the subgroup of patients without a history of OHE. In subgroup analyses, MHE (defined by PHES) was associated with OHE development in patients with CP B, whereas there was no association in patients with CP A or C. In the subgroup of patients with available S-ANT1, MHE (defined by S-ANT1) was independently associated with OHE development. Combined testing (PHES+S-ANT1) was superior to single testing for predicting OHE and poorer LTx-free survival. Conclusions This large multicenter study demonstrates that screening for MHE is a useful tool for predicting OHE and poorer survival

Revisiting the role of insulin-like growth factor-I receptor stimulating activity and the apolipoprotein E in Alzheimer's disease

__Background:__ Alterations in insulin-like growth factor I (IGF-I) signaling have been associated with dementia and Alzheimer's disease (AD). Studies on the association between IGF-I levels and dementia risk have been inconclusive. We reported earlier that higher levels of IGF-I receptor stimulating activity are associated with a higher prevalence and incidence of dementia. __Objective:__ In the present study, we test the robustness of the association between IGF-I receptor stimulating activity and dementia by extending the follow-up period to 16 years and investigate possible effect modification by apolipoprotein E (ApoE). __Methods:__ At baseline, circulating IGF-I receptor stimulating activity was determined by the IGF-I kinase receptor activation (KIRA) assay in 1,014 elderly from the Rotterdam Study. Dementia was assessed from baseline (1997-1999) to follow-up in January 2015. Associations of IGF-I receptor stimulating activity and incident dementia were assessed with Cox proportional hazards models. __Results:__ During 10,752 person-years of follow-up, 174 people developed dementia. In the extended follow-up we no longer observed a dose-response relationship between IGF-I receptor stimulating activity and risk of dementia [adjusted odd

Age- and Tumor Subtype-Specific Breast Cancer Risk Estimates for CHEK2*1100delC Carriers.

PURPOSE: CHEK2*1100delC is a well-established breast cancer risk variant that is most prevalent in European populations; however, there are limited data on risk of breast cancer by age and tumor subtype, which limits its usefulness in breast cancer risk prediction. We aimed to generate tumor subtype- and age-specific risk estimates by using data from the Breast Cancer Association Consortium, including 44,777 patients with breast cancer and 42,997 controls from 33 studies genotyped for CHEK2*1100delC. PATIENTS AND METHODS: CHEK2*1100delC genotyping was mostly done by a custom Taqman assay. Breast cancer odds ratios (ORs) for CHEK2*1100delC carriers versus noncarriers were estimated by using logistic regression and adjusted for study (categorical) and age. Main analyses included patients with invasive breast cancer from population- and hospital-based studies. RESULTS: Proportions of heterozygous CHEK2*1100delC carriers in controls, in patients with breast cancer from population- and hospital-based studies, and in patients with breast cancer from familial- and clinical genetics center-based studies were 0.5%, 1.3%, and 3.0%, respectively. The estimated OR for invasive breast cancer was 2.26 (95%CI, 1.90 to 2.69; P = 2.3 × 10(-20)). The OR was higher for estrogen receptor (ER)-positive disease (2.55 [95%CI, 2.10 to 3.10; P = 4.9 × 10(-21)]) than it was for ER-negative disease (1.32 [95%CI, 0.93 to 1.88; P = .12]; P interaction = 9.9 × 10(-4)). The OR significantly declined with attained age for breast cancer overall (P = .001) and for ER-positive tumors (P = .001). Estimated cumulative risks for development of ER-positive and ER-negative tumors by age 80 in CHEK2*1100delC carriers were 20% and 3%, respectively, compared with 9% and 2%, respectively, in the general population of the United Kingdom. CONCLUSION: These CHEK2*1100delC breast cancer risk estimates provide a basis for incorporating CHEK2*1100delC into breast cancer risk prediction models and into guidelines for intensified screening and follow-up.NIH

Genome-wide association study of germline variants and breast cancer-specific mortality.

BackgroundWe examined the associations between germline variants and breast cancer mortality using a large meta-analysis of women of European ancestry.MethodsMeta-analyses included summary estimates based on Cox models of twelve datasets using ~10.4 million variants for 96,661 women with breast cancer and 7697 events (breast cancer-specific deaths). Oestrogen receptor (ER)-specific analyses were based on 64,171 ER-positive (4116) and 16,172 ER-negative (2125) patients. We evaluated the probability of a signal to be a true positive using the Bayesian false discovery probability (BFDP).ResultsWe did not find any variant associated with breast cancer-specific mortality at P &lt; 5 × 10-8. For ER-positive disease, the most significantly associated variant was chr7:rs4717568 (BFDP = 7%, P = 1.28 × 10-7, hazard ratio [HR] = 0.88, 95% confidence interval [CI] = 0.84-0.92); the closest gene is AUTS2. For ER-negative disease, the most significant variant was chr7:rs67918676 (BFDP = 11%, P = 1.38 × 10-7, HR = 1.27, 95% CI = 1.16-1.39); located within a long intergenic non-coding RNA gene (AC004009.3), close to the HOXA gene cluster.ConclusionsWe uncovered germline variants on chromosome 7 at BFDP &lt; 15% close to genes for which there is biological evidence related to breast cancer outcome. However, the paucity of variants associated with mortality at genome-wide significance underpins the challenge in providing genetic-based individualised prognostic information for breast cancer patients