Functional principles of steerable multi‐element probes in insects

Hemipterans, mosquitoes, and parasitic wasps probe in a variety of substrates to find hosts for their larvae or food sources. Probes capable of sensing and precise steering enable insects to navigate through solid substrates without visual information and to reach targets that are hidden deep inside the substrate. The probes belong to non‐related taxa and originate from abdominal structures (wasps) or mouthparts (hemipterans and mosquitoes), but nevertheless share several morphological characteristics. Although the transport function clearly differs (egg laying and acquisition of liquid food), the functional demands on the mechanical behaviour of the probe within the substrate tend to be similar. The probe needs to be thin to limit substrate deformation, and long, in order to attain substantial path lengths or depths. We linked the morphology across taxa to the different functional requirements, to provide insights into the biology of probing insects and the evolution of their probes. Current knowledge of insect probes is spread over many taxa, which offers the possibility to derive general characteristics of insect probing. Buckling during initial puncturing is limited by external support mechanisms. The probe itself consist of multiple (3–6) parts capable of sliding along one another. This multi‐part construction presumably enables advancement and precise three‐dimensional steering of the probe through the substrate with very low net external pushing forces, preventing buckling during substrate penetration. From a mechanical viewpoint, a minimum of three elements is required for 3D steering and volumetric exploration, as realised in the ovipositors of wasps. More elements, such as in six‐element probes of mosquitoes, may enhance friction in soft substrates. Alternatively, additional elements can have functions other than ‘drilling’, such as saliva injection in mosquitoes. Despite the gross similarities, probes show differences in their cross sections, tip morphologies, relative lengths of their elements, and the shape of their interconnections. The hypothesis is that the probe morphology is influenced by the substrate properties, which are mostly unknown. Correlating the observed diversity to substrate‐specific functional demands is therefore currently impossible. We conclude that a multipart probe with sliding elements is highly effective for volumetric substrate probing. Shared functional demands have led to an evolutionary convergence of slender multi‐element probes in disparate insect taxa. To fully understand 3D probing, it is necessary to study the sensory and material properties, as well as the detailed kinematics and dynamics of the various probes in relation to the nature of the selective pressure originating from the species‐specific substrates. Such knowledge will deepen our understanding of probing mechanisms and may support the development of slender, bio‐inspired probes.     

Handgrip strength and mortality in the oldest old population: the Leiden 85-plus study

Background

Poor muscular strength has been shown to be associated with increased morbidity and mortality in diverse samples of middle-aged and elderly people. However, the oldest old population (i.e., over 85 years) is underrepresented in such studies. Our objective was to assess the association between muscular strength and mortality in the oldest old population.

Methods

We included 555 participants (65% women) from the Leiden 85-plus study, a prospective population-based study of all 85-year-old inhabitants of Leiden, Netherlands. We measured the handgrip strength of participants at baseline and again at age 89 years. We collected baseline data on comorbidities, functional status, levels of physical activity, and adjusted for potential confounders. During the follow-up period, we collected data on mortality.

Results

During a follow-up period of 9.5 years (range 8.5–10.5 years), 444 (80%) participants died. Risk for all-cause mortality was elevated among participants in the lowest tertile of handgrip strength at age 85 years (hazard ratio [HR] 1.35, 95% confidence interval [CI] 1.00–1.82, p = 0.047) and the lowest two tertiles of handgrip strength at age 89 years (HR 2.04, CI 1.24–3.35, p = 0.005 and HR 1.73, CI 1.11–2.70, p = 0.016). We also observed significantly increased mortality among participants in the tertile with the highest relative loss of handgrip strength over four years (HR 1.72, CI 1.07–2.77, p = 0.026).

Interpretation

Handgrip strength, a surrogate measurement of overall muscular strength, is a predictor of all-cause mortality in the oldest old population and may serve as a convenient tool for prognostication of mortality risk among elderly people.The fastest growing segment of the elderly population is the group older than 85 years, which is classified as the oldest old age group.^1,2 The average rate of growth of this group is reported to be 3.8% annually at a global level. By 2050, the oldest old age group will account for one-fifth of all older persons.²Inactivity is a major problem in this age group, owing to an increased prevalence of medical comorbidities and physical disability with age. Age-related stereotypes and misconceptions (e.g., that older people are invariably unhealthy), coupled with a perceived lack of benefits provided by physical activity, can also represent obstacles to exercise among the oldest old population.The predisposing influence of a sedentary lifestyle on age-related cardiometabolic diseases (i.e., obesity, type 2 diabetes mellitus, hypertension and coronary artery disease) is well established. Evidence of the protective effects of physical activity against certain cancers, falls and mental health problems is accumulating.^3,4 Lack of exercise is also a significant risk factor for sarcopenia,^5,6 a progressive loss of skeletal muscle mass and strength with aging.⁷ Sarcopenia is highly prevalent among those aged 80 years and older, with reported rates exceeding 50%.⁸ Reduced muscular strength is associated in turn with outcomes such as physical disability,^9,10 cognitive decline¹¹ and mortality.^12,13Handgrip strength, a simple bedside tool, has been shown to be a valid surrogate measurement of overall muscular strength.^14,15 A recent systematic review has shown that low handgrip strength is associated consistently with premature mortality, disability and other health-related complications among various samples of middle-aged and older people.¹⁶ Despite its prognostic value, handgrip dynamometry is rarely used in routine geriatric assessment. Epidemiologic studies evaluating the relation in the population of the oldest old are also lacking. We tested the association between handgrip strength and mortality in a prospective population-based study of the oldest old age group. We obtained approval for our study from the Medical Ethical Committee of the Leiden University Medical Center, and informed consent from all participants.     

NT-proBNP Best Predictor of Cardiovascular Events and Cardiovascular Mortality in Secondary Prevention in Very Old Age: The Leiden 85-Plus Study

Background

In the aging population cardiovascular disease (CVD) is highly prevalent. Identification of very old persons at high risk of recurrent CVD is difficult, since traditional risk markers loose predictive value with age.

Methods

In a population-based sample of 282 85-year old participants with established CVD from the Leiden 85-plus Study, we studied predictive values of traditional cardiovascular risk markers, a history of major CVD (myocardial infarction, stroke or arterial surgery), and new cardiovascular biomarkers (estimated glomerular filtration rate (MDRD), C-reactive protein (CRP), homocysteine and N-terminal pro B-type natriuretic peptide (NT-proBNP)) regarding 5-year risk of recurrent cardiovascular events and mortality (composite endpoint).

Results

During complete 5-year follow-up 157 (56%) participants died. 109 (39%) had a cardiovascular event or died from cardiovascular causes. Individually related to the composite endpoint were: a history of major CVD (HR 1.5 (95%CI 1.03-2.3)), CRP (HR 1.3 (95%CI 1.03-1.5)), homocysteine (HR 1.4 (95%CI 1.2-2.6)) and NT-proBNP (HR 1.7 (95%CI 1.4-2.1)). A prediction model including all traditional risk markers yielded a C-statistic of 0.59 (95%CI 0.52-0.66). Of all five new markers only addition of NT-proBNP improved the C-statistic (0.67 (95%CI 0.61-0.74, p=0.023)). The categoryless net reclassification improvement for NT-proBNP was 39% (p=0.001), for a history of major CVD 27.2% (p=0.03) and for homocysteine 24.7% (p=0.04).

Conclusions

Among very old subjects with established CVD, NT-proBNP was the strongest risk marker for cardiovascular events and cardiovascular mortality. When estimating risk in secondary prevention in very old age, use of NT-proBNP should be considered.     

Level of Satisfaction of Older Persons with Their General Practitioner and Practice: Role of Complexity of Health Problems

Background

Satisfaction is widely used to evaluate and direct delivery of medical care; a complicated relationship exists between patient satisfaction, morbidity and age. This study investigates the relationships between complexity of health problems and level of patient satisfaction of older persons with their general practitioner (GP) and practice.

Methods and Findings

This study is embedded in the ISCOPE (Integrated Systematic Care for Older Persons) study. Enlisted patients aged ≥75 years from 59 practices received a written questionnaire to screen for complex health problems (somatic, functional, psychological and social). For 2664 randomly chosen respondents (median age 82 years; 68% female) information was collected on level of satisfaction (satisfied, neutral, dissatisfied) with their GP and general practice, and demographic and clinical characteristics including complexity of health problems. Of all participants, 4% was dissatisfied with their GP care, 59% neutral and 37% satisfied. Between these three categories no differences were observed in age, gender, country of birth or education level. The percentage of participants dissatisfied with their GP care increased from 0.4% in those with 0 problem domains to 8% in those with 4 domains, i.e. having complex health problems (p<0.001). Per additional health domain with problems, the risk of being dissatisfied increased 1.7 times (95% CI 1.4–2.14; p<0.001). This was independent of age, gender, and demographic and clinical parameters (adjusted OR 1.4, 95% CI 1.1–1.8; p = 0.021).

Conclusion

In older persons, dissatisfaction with general practice is strongly correlated with rising complexity of health problems, independent of age, demographic and clinical parameters. It remains unclear whether complexity of health problems is a patient characteristic influencing the perception of care, or whether the care is unable to handle the demands of these patients. Prospective studies are needed to investigate the causal associations between care organization, patient characteristics, indicators of quality, and patient perceptions.     

Variability in Vulnerability Assessment of Older People by Individual General Practitioners: A Cross-Sectional Study

Background

In clinical practice, GPs appeared to have an internalized concept of “vulnerability.” This study investigates the variability between general practitioners (GPs) in their vulnerability-assessment of older persons.

Methods

Seventy-seven GPs categorized their 75-plus patients (n = 11392) into non-vulnerable, possibly vulnerable, and vulnerable patients. GPs personal and practice characteristics were collected. From a sample of 2828 patients the following domains were recorded: sociodemographic, functional [instrumental activities in daily living (IADL), basic activities in daily living (BADL)], somatic (number of diseases, polypharmacy), psychological (Mini-Mental State Examination, 15-item Geriatric Depression Scale; GDS-15) and social (De Jong-Gierveld Loneliness Scale; DJG). Variability in GPs'' assessment of vulnerability was tested with mixed effects logistic regression. P-values for variability (p_var) were calculated by the log-likelihood ratio test.

Results

Participating GPs assessed the vulnerability of 10,361 patients. The median percentage of vulnerable patients was 32.0% (IQR 19.5 to 40.1%). From the somatic and psychological domains, GPs uniformly took into account the patient characteristics ‘total number of diseases’ (OR 1.7, 90% range  = 0, p_var = 1), ‘polypharmacy’ (OR 2.3, 90% range  = 0, p_var = 1) and ‘GDS-15’ (OR 1.6, 90% range  = 0, p_var = 1). GPs vary in the way they assessed their patients'' vulnerability in the functional domain (IADL: median OR 2.8, 90% range 1.6, p_var<0.001, BADL: median OR 2.4, 90% range 2.9, p_var<0.001) and the social domain (DJG: median OR 1.2, 90% range  = 1.2, p_var<0.001).

Conclusions

GPs seem to share a medical concept of vulnerability, since they take somatic and psychological characteristics uniformly into account in the vulnerability-assessment of older persons. In the functional and social domains, however, variability was found. Vulnerability assessment by GPs might be a promising instrument to select older people for geriatric care if more uniformity could be achieved.

Trial Registration

Netherlands Trial Register NTR1946     

Blood Pressure Variability and Cardiovascular Risk in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER)

Variability in blood pressure predicts cardiovascular disease in young- and middle-aged subjects, but relevant data for older individuals are sparse. We analysed data from the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) study of 5804 participants aged 70–82 years with a history of, or risk factors for cardiovascular disease. Visit-to-visit variability in blood pressure (standard deviation) was determined using a minimum of five measurements over 1 year; an inception cohort of 4819 subjects had subsequent in-trial 3 years follow-up; longer-term follow-up (mean 7.1 years) was available for 1808 subjects. Higher systolic blood pressure variability independently predicted long-term follow-up vascular and total mortality (hazard ratio per 5 mmHg increase in standard deviation of systolic blood pressure = 1.2, 95% confidence interval 1.1–1.4; hazard ratio 1.1, 95% confidence interval 1.1–1.2, respectively). Variability in diastolic blood pressure associated with increased risk for coronary events (hazard ratio 1.5, 95% confidence interval 1.2–1.8 for each 5 mmHg increase), heart failure hospitalisation (hazard ratio 1.4, 95% confidence interval 1.1–1.8) and vascular (hazard ratio 1.4, 95% confidence interval 1.1–1.7) and total mortality (hazard ratio 1.3, 95% confidence interval 1.1–1.5), all in long-term follow-up. Pulse pressure variability was associated with increased stroke risk (hazard ratio 1.2, 95% confidence interval 1.0–1.4 for each 5 mmHg increase), vascular mortality (hazard ratio 1.2, 95% confidence interval 1.0–1.3) and total mortality (hazard ratio 1.1, 95% confidence interval 1.0–1.2), all in long-term follow-up. All associations were independent of respective mean blood pressure levels, age, gender, in-trial treatment group (pravastatin or placebo) and prior vascular disease and cardiovascular disease risk factors. Our observations suggest variability in diastolic blood pressure is more strongly associated with vascular or total mortality than is systolic pressure variability in older high-risk subjects.     

Predictive Value of a Profile of Routine Blood Measurements on Mortality in Older Persons in the General Population: The Leiden 85-Plus Study

BackgroundVarious questionnaires and performance tests predict mortality in older people. However, most are heterogeneous, laborious and a validated consensus index is not available yet. Since most older people are regularly monitored by laboratory tests, we compared the predictive value of a profile of seven routine laboratory measurements on mortality in older persons in the general population with other predictors of mortality; gait speed and disability in instrumental activities of daily living (IADL).Conclusions/SignificanceIn the general population of oldest old, the number of abnormalities in seven routine laboratory measurements predicts five-year mortality as accurately as gait speed and IADL disability.     

The relevance of tissue thiol histochemistry to diagnostic hematopathology

Expression analyses suggest that alterations of the antioxidant state of some diffuse large B-cell lymphomas can assist prognosis; reversibly oxidized thiols may serve as a surrogate marker for identifying such cases. Little is known about the distribution of free thiols and reversibly oxidized thiols in human tissues. We developed a staining technique that enables visualization of tissue thiols in situ using bright field microscopy and validated it using gastrointestinal tissue specimens. We used our thiol staining technique to assess benign tonsillectomy and diffuse large B-cell lymphoma specimens. The gastrointestinal series revealed the presence of free thiols within epithelial cells and cells of the lamina propria. Staining for reversibly oxidized thiols was robust in gastric foveolar cells, intestinal goblet cells and the mucus they produce. Tonsillectomy specimens exhibited diffuse presence of free thiols. Staining for reversibly oxidized thiols was confined to germinal center macrophages and sinus histiocytes. Among the diffuse large B-cell lymphoma specimens, we observed strong staining for free thiols within malignant cells. By contrast to benign B-cells, the malignant cells demonstrated pronounced and diffuse staining for reversibly oxidized thiols. We demonstrated intrinsic differences between benign and malignant cells.     

A single camera roentgen stereophotogrammetry method for static displacement analysis

A new method to quantify motion or deformation of bony structures has been developed, since quantification is often difficult due to overlaying tissue, and the currently used roentgen stereophotogrammetry method requires significant investment. In our method, a single stationary roentgen source is used, as opposed to the usual two, which, in combination with a fixed radiogram cassette holder, forms a camera with constant interior orientation. By rotating the experimental object, it is possible to achieve a sufficient angle between the various viewing directions, enabling photogrammetric calculations. The photogrammetric procedure was performed on digitised radiograms and involved template matching to increase accuracy. Co-ordinates of spherical markers in the head of a bird (Rhea americana), were calculated with an accuracy of 0.12mm. When these co-ordinates were used in a deformation analysis, relocations of about 0.5mm could be accurately determined.     

微机在牙形刺研究中的应用

该文对微机在牙形刺研究中的应用方法上进行了探索,在大量原始资料和数据的基础上,采用了模糊聚类分析和CAI计算机程序系统的研究,在地层划分,化石组合,沉积环境分析及生油气评价等方面都取得了一定的成果。