Tuning the performance of a natural treatment process using metagenomics for improved trace organic chemical attenuation.

By utilizing high-throughput sequencing and metagenomics, this study revealed how the microbial community characteristics including composition, diversity, as well as functional genes in managed aquifer recharge (MAR) systems can be tuned to enhance removal of trace organic chemicals of emerging concern (CECs). Increasing the humic content of the primary substrate resulted in higher microbial diversity. Lower concentrations and a higher humic content of the primary substrate promoted the attenuation of biodegradable CECs in laboratory and field MAR systems. Metagenomic results indicated that the metabolic capabilities of xenobiotic biodegradation were significantly promoted for the microbiome under carbon-starving conditions.

Multisensory cues improve sensorimotor synchronisation.

Synchronising movements with events in the surrounding environment is an ubiquitous aspect of everyday behaviour. Often, information about a stream of events is available across sensory modalities. While it is clear that we synchronise more accurately to auditory cues than other modalities, little is known about how the brain combines multisensory signals to produce accurately timed actions. Here, we investigate multisensory integration for sensorimotor synchronisation. We extend the prevailing linear phase correction model for movement synchronisation, describing asynchrony variance in terms of sensory, motor and timekeeper components. Then we assess multisensory cue integration, deriving predictions based on the optimal combination of event time, defined across different sensory modalities. Participants tapped in time with metronomes presented via auditory, visual and tactile modalities, under either unimodal or bimodal presentation conditions. Temporal regularity was manipulated between modalities by applying jitter to one of the metronomes. Results matched the model predictions closely for all except high jitter level conditions in audio-visual and audio-tactile combinations, where a bias for auditory signals was observed. We suggest that, in the production of repetitive timed actions, cues are optimally integrated in terms of both sensory and temporal reliability of events. However, when temporal discrepancy between cues is high they are treated independently, with movements timed to the cue with the highest sensory reliability.

Ceratoscopelus maderensis: peculiar sound-scattering layer identified with this myctophid fish.

A sound-scattering layer, composed of discrete hyperbolic echosequences and apparently restricted to the Slope Water region of the western North Atlantic, has been identified from the Deep Submergence Research Vehicle Alvin with schools of the meyctophid fish Ceratoscopelus maderensis. By diving into the layer and using Alvin's echo-ranging sonar, we approached and visually identified the sound scatterers. The number of echo sequences observed with the surface echo-soutnder (1/23.76 x 10(5) cubic meters of water) checked roughly with the number of sonar targets observed from the submarine (1/7.45 x 105 cubic meters). The fish schools appeared to be 5 to 10 meters thick, 10 to 100 meters in diameter, and on centers 100 to 200 meters apart. Density within schools was estimated at 10 to 15 fish per cubic meter.

Being discrete helps keep to the beat.

Synchronizing our actions with external events is a task we perform without apparent effort. Its foundation relies on accurate temporal control that is widely accepted to take one of two different modes of implementation: explicit timing for discrete actions and implicit timing for smooth continuous movements. Here we assess synchronisation performance for different types of action and test the degree to which each action supports corrective updating following changes in the environment. Participants performed three different finger actions in time with an auditory pacing stimulus allowing us to assess synchronisation performance. Presenting a single perturbation to the otherwise regular metronome allowed us to examine corrections supported by movements varying in their mode of timing implementation. We find that discrete actions are less variable and support faster error correction. As such, discrete actions may be preferred when engaging in time-critical adaptive behaviour with people and objects in a dynamic environment.

Multiple sclerosis and faecal microbiome transplantation: are you going to eat that?

Gut microbiome interaction goes beyond commensal function as vitamin production or support nutrients digestion. It also interplays with the host immune system and may be related to the development of immune-mediated diseases. Multiple sclerosis patients have dysbiosis compared to healthy individuals. But how this relates to disease development and severity is still uncertain. Dietary change including probiotic mixtures or ketogenic regimen has proven to change microbiome in multiple sclerosis (MS) subjects to one similar to healthy controls. However, proof of clinical benefits is lacking. We dissert on current knowledge about immune system and gut bacteria interactions. We discuss faecal microbial transplantation as a potential intervention to ameliorate gut dysbiosis in MS as well as the caveats of a clinical trial design.

Motor control: Mechanisms of motor equivalence in handwriting.

Handwriting is a classic example of how the details of movement can be scale and plane invariant: letter forms reflecting personal style are unchanged, whether one is writing on a piece of paper, on a blackboard or in the sand using the foot. Recent research points to a role for the parietal cortex in such motor equivalence.

Human bipedal instability in tree canopy environments is reduced by "light touch" fingertip support.

Whether tree canopy habitats played a sustained role in the ecology of ancestral bipedal hominins is unresolved. Some argue that arboreal bipedalism was prohibitively risky for hominins whose increasingly modern anatomy prevented them from gripping branches with their feet. Balancing on two legs is indeed challenging for humans under optimal conditions let alone in forest canopy, which is physically and visually highly dynamic. Here we quantify the impact of forest canopy characteristics on postural stability in humans. Viewing a movie of swaying branches while standing on a branch-like bouncy springboard destabilised the participants as much as wearing a blindfold. However "light touch", a sensorimotor strategy based on light fingertip support, significantly enhanced their balance and lowered their thigh muscle activity by up to 30%. This demonstrates how a light touch strategy could have been central to our ancestor's ability to avoid falls and reduce the mechanical and metabolic cost of arboreal feeding and movement. Our results may also indicate that some adaptations in the hand that facilitated continued access to forest canopy may have complemented, rather than opposed, adaptations that facilitated precise manipulation and tool use.

Characteristics in youth indicative of adult-onset Hodgkin's disease.

From the college entrance health data of 50,000 male former students, the records of 45 who eventually died of Hodgkin's disease were compared with those of 180 surviving classmates with reference to certain indicator characteristics. Risk ratios of Hodgkin's disease tended to be lower for men who had experienced various common contagious diseases in childhood. This reduced incidence of clinical contagions may signify that: 1) Inadequate early challenge of immune mechanisms left subjects more susceptible to later Hodgkin's disease, whether or not it is of infectious origin; 2) heightened immune mechanisms that led to subclinical attacks of early contagious diseases promoted an autoimmune response that evolved as Hodgkin's disease; or 3) early childhood infections eliminated some subjects who otherwise would have attended college and ultimately developed adult-onset Hodgkin's disease. Also, Hodgkin's disease risk was higher for students who had reported early death of a parent, particularly from cancer. Moreover, the risk tended to be increased among collegians who were obese, heavy cigarette smokers, and coffee drinkers. None of these indicator characteristics was associated with 89 fatal lymphomas of other types that occurred in the same study population.

Calcium, vitamin D, and the occurrence of colorectal cancer among women.

BACKGROUND: Despite evidence from animal studies for a protective effect of higher calcium and possibly vitamin D intake against colorectal cancer, epidemiologic studies have been inconclusive. PURPOSE: We investigated the associations between the intake of calcium and vitamin D and the occurrence of colorectal cancer. METHODS: In a prospective study, 89 448 female registered nurses who were free of cancer responded to a mailed, semiquantitative food-frequency questionnaire in 1980; dietary information was updated in 1984 and 1986. Through 1992, 501 incident cases of colorectal cancer (396 colon and 105 rectal cancers) were documented. As measures of exposure, we used nutrient intake in 1980 and also two measures of long-term intake on the basis of the three questionnaires: the average of intakes from the three questionnaires and consistent intakes, which were defined as high if women were in the upper tertile on all questionnaires and low if they were in the lower tertile on all questionnaires. To further characterize long-term intake, we conducted analyses excluding women who reported a change in their consumption of milk (primary source of calcium and vitamin D) in the 10 years prior to 1980. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using the lowest quintile of intake as a reference. The Mantel extension test was used to evaluate linear trends across the categories of nutrient intake. In multivariate analyses, the trends were tested with use of the medians of the intake as a continuous variable in the logistic model. The P values for the trends were two-sided. RESULTS: On the basis of the data from the 1980 questionnaire alone, the multivariate RR for colorectal cancer for women in the upper versus the lower quintile were 0.80 (95% CI = 0.60-1.07) for dietary calcium, 0.84 (95% CI = 0.63-1.13) for dietary vitamin D (from foods only), and 0.88 (95% CI = 0.66-1.16) for total vitamin D (from foods and supplements). After the exclusion of women who reported a change in their milk intake, the RRs for colorectal cancer for the highest versus the lowest categories of average intake were 0.74 (95% CI = 0.36-1.50) for dietary calcium, 0.72 (95% CI = 0.34-1.54) for dietary vitamin D, and 0.42 (95% CI = 0.19-0.91) for total vitamin D. The corresponding RRs for the consistency analyses were 0.70 (95% CI = 0.35-1.39) for dietary calcium, 0.59 (95% CI = 0.30- 1.16) for dietary vitamin D, and 0.33 (95% CI = 0.16-0.70) for total vitamin D. CONCLUSIONS: These findings do not support a substantial inverse association between calcium intake and risk of colorectal cancer, but an inverse association between intake of total vitamin D and risk of colorectal cancer was suggested. IMPLICATIONS: Available evidence does not warrant an increase in calcium intake to prevent colon cancer, but longer-term studies of both calcium and especially vitamin D in relation to colorectal cancer risk are needed.

Dietary fiber, glycemic load, and risk of NIDDM in men.

OBJECTIVE: Intake of carbohydrates that provide a large glycemic response has been hypothesized to increase the risk of NIDDM, whereas dietary fiber is suspected to reduce incidence. These hypotheses have not been evaluated prospectively. RESEARCH DESIGN AND METHODS: We examined the relationship between diet and risk of NIDDM in a cohort of 42,759 men without NIDDM or cardiovascular disease, who were 40-75 years of age in 1986. Diet was assessed at baseline by a validated semiquantitative food frequency questionnaire. During 6-years of follow-up, 523 incident cases of NIDDM were documented. RESULTS: The dietary glycemic index (an indicator of carbohydrate's ability to raise blood glucose levels) was positively associated with risk of NIDDM after adjustment for age, BMI, smoking, physical activity, family history of diabetes, alcohol consumption, cereal fiber, and total energy intake. Comparing the highest and lowest quintiles, the relative risk (RR) of NIDDM was 1.37 (95% CI, 1.02-1.83, P trend = 0.03). Cereal fiber was inversely associated with risk of NIDDM (RR = 0.70; 95% CI, 0.51-0.96, P trend = 0.007; for > 8.1 g/day vs. < 3.2 g/day). The combination of a high glycemic load and a low cereal fiber intake further increased the risk of NIDDM (RR = 2.17, 95% CI, 1.04-4.54) when compared with a low glycemic load and high cereal fiber intake. CONCLUSIONS: These findings support the hypothesis that diets with a high glycemic load and a low cereal fiber content increase risk of NIDDM in men. Further, they suggest that grains should be consumed in a minimally refined form to reduce the incidence of NIDDM.

Biotransformation of trace organic chemicals during groundwater recharge: How useful are first-order rate constants?

This study developed relationships between the attenuation of emerging trace organic chemicals (TOrC) during managed aquifer recharge (MAR) as a function of retention time, system characteristics, and operating conditions using controlled laboratory-scale soil column experiments simulating MAR. The results revealed that MAR performance in terms of TOrC attenuation is primarily determined by key environmental parameters (i.e., redox, primary substrate). Soil columns with suboxic and anoxic conditions performed poorly (i.e., less than 30% attenuation of moderately degradable TOrC) in comparison to oxic conditions (on average between 70-100% attenuation for the same compounds) within a residence time of three days. Given this dependency on redox conditions, it was investigated if key parameter-dependent rate constants are more suitable for contaminant transport modeling to properly capture the dynamic TOrC attenuation under field-scale conditions. Laboratory-derived first-order removal kinetics were determined for 19 TOrC under three different redox conditions and rate constants were applied to MAR field data. Our findings suggest that simplified first-order rate constants will most likely not provide any meaningful results if the target compounds exhibit redox dependent biotransformation behavior or if the intention is to exactly capture the decline in concentration over time and distance at field-scale MAR. However, if the intention is to calculate the percent removal after an extended time period and subsurface travel distance, simplified first-order rate constants seem to be sufficient to provide a first estimate on TOrC attenuation during MAR.

Hypertension and cardiovascular risk factors in hemodialyzed diabetic patients.

In a retrospective study, the cause of death and the cardiovascular risk conferred by hypertension and other risk factors were analyzed in 200 diabetic and 200 nondiabetic patients who were matched for age, sex, year of admission, and center of treatment. Total and cardiovascular mortality were considerably higher in diabetics, cardiovascular mortality being 4.8 times higher in patients with type I and 3.0 times higher in those with type II diabetes compared to matched controls. Cardiovascular mortality progressively increased with age and had not improved in recent years. In both types I and II diabetes, the rate (58%) and proportion (38%) of deaths from cardiovascular causes were significantly higher in diabetics than in matched controls. Myocardial infarction (13%) and stroke (7%) accounted only for a minority of cardiovascular mortality, the majority (80%) being due to "sudden death of unknown cause." Autopsy was carried out in 33% of patients with sudden death. A documented history of long-standing hypertension increased cardiovascular death in diabetic more than in nondiabetic patients. Diabetic retinopathy (an index of microangiopathy) and absence of peripheral pulses, amputation, or history of myocardial infarction, stroke, or transient ischemic attacks (as evidence of macroangiopathy) caused surprisingly little increase in relative risk for cardiovascular death. In diabetics but not in nondiabetics, cardiomegaly, particularly in association with electrocardiographic abnormalities, was a strong predictor of cardiovascular death.

Pharmacokinetics and concentration-effect relationships of intervenous and oral clonidine.

The kinetics of the disposition of intravenous and oral clonidine in five normotensive subjects have been determined. It is proposed that a two-compartment model adequately describes the disposition of the drug. The drug is rapidly distributed (t1/2alpha = 10.8 +/- 4.7 min) but slowly elimainated (t1/2beta = 8.5 +/- 0.9 hr). The bioavailability of oral clonidine in the tablets tested averaged 75.2% and 40 to 50% of the bioavailable dose is excreted unchanged in urine. Renal clearance of the drug showed considerable intersubject variation (1.82 +/- 0.34 ml/min/kg) and exceed the calculated glomerular filtration rate in some subjects. Oral and intravenous clonidine induced significant falls in blood pressure (greater than 20/15 mm Hg) in our normotensive subjects and consistently caused marked sedation and dryness of the mouth. Sedation and salivary flow correlated with plasma clonidine concentration over the range 0 to 4 ng/ml. Falls in blood pressure were related to plasma concentration to 1.5 to 2 ng/ml but at higher concentrations the hypotensive effect was attenuated.

A prospective study of diet and the risk of symptomatic diverticular disease in men.

To examine the association between dietary fiber, sources of fiber, other nutrients, and the diagnosis of symptomatic diverticular disease, we analyzed data from a prospective cohort of 47,888 US men. During 4 y of follow-up we documented 385 new cases of symptomatic diverticular disease. Total dietary fiber intake was inversely associated with the risk of diverticular disease after adjustment for age, energy-adjusted total fat intake, and physical activity [relative risk (RR) 0.58; 95% CI 0.41, 0.83; P for trend = 0.01 for men in the highest as compared with the lowest quintile of dietary fiber]. This inverse association was primarily due to fruit and vegetable fiber. For men on a high-total-fat, low-fiber diet, the RR was 2.35 (95% CI 1.38, 3.98) compared with those on a low-total-fat, high-fiber diet, and for men on a high-red-meat, low-fiber diet the RR was 3.32 (95% CI 1.46, 7.53) compared with those on a low-red-meat, high-fiber diet. These prospective data support the hypothesis that a diet low in total dietary fiber increases the incidence of symptomatic diverticular disease. They also provide evidence that the combination of high intake of total fat or red meat and a diet low in total dietary fiber particularly augments the risk.

The role of physical exercise in the occurrence of Parkinson's disease.

A case-control study of Parkinson's disease and physical exercise was conducted in a cohort of 50,002 men who attended Harvard College (Cambridge, Mass) or the University of Pennsylvania (Philadelphia) between 1916 and 1950 and were followed up in adulthood for morbidity and mortality data. Cases of Parkinson's disease were identified from responses to mailed questionnaires and death certificates through 1978. Four controls from the same population were selected for each case. The association between physical activity at the time of college and subsequent risk of Parkinson's disease was evaluated for 137 cases and 548 controls, whereas the data on physical activity in adulthood before the disease occurrence was available only for 94 of these cases. Having belonged to a varsity team or having done regular physical exercise in college was associated with a lower nonsignificant risk of Parkinson's disease. In adulthood, practice of moderate or heavy sports was linked to a reduced risk, although more precise analysis revealed that there was only a modest nonsignificant reduction in risk for subjects who do a moderate amount of physical exercise, but this negative association disappears at higher levels of physical expenditure. These results, which require further confirmation, are compatible with a slight protective effect of physical exercise on the risk of Parkinson's disease, although the lack of association cannot be refuted.

A comparison of the rate of pinch grip force increases and decreases in parkinsonian bradykinesia.

Two cases of untreated patients with asymmetric bradykinetic symptoms are described. In the more affected hand, the production of decreases in isometric pinch grip force is slowed more than increases.

Coordination of aimed movements in a case of unilateral cerebellar damage.

We have studied multi-joint arm movements in a patient with right cerebellar damage. Our patient's kinetic tremor was reduced in the absence of visual feedback, but increased when performing a concurrent cognitive task. We suggest that her kinetic tremor reflects use of a slow cortical feedback circuit for error-corrections during movement. Analysing the spatial relation between hand aperture and hand transport in prehensile movements, we found preserved strategic, trial-to-trial coordination, but impaired reactive, within-trial coordination. We conclude that the proprioceptive representations provided by the normal cerebellum play an important role in coordinating multi-joint movement.

Brain activity correlates differentially with increasing temporal complexity of rhythms during initialisation, synchronisation, and continuation phases of paced finger tapping.

Activity in parts of the human motor system has been shown to correlate with the complexity of performed motor sequences in terms of the number of limbs moved, number of movements, and number of trajectories. Here, we searched for activity correlating with temporal complexity, in terms of the number of different intervals produced in the sequence, using an overlearned tapping task. Our task was divided into three phases: movement selection and initiation (initiate), synchronisation of finger tapping with an external auditory cue (synchronise), and continued tapping in absence of the auditory pacer (continue). Comparisons between synchronisation and continuation showed a pattern in keeping with prior neuroimaging studies of paced finger tapping. Thus, activation of bilateral SMA and basal ganglia was greater in continuation tapping than in synchronisation tapping. Parametric analysis revealed activity correlating with temporal complexity during initiate in bilateral supplementary and pre-supplementary motor cortex (SMA and preSMA), rostral dorsal premotor cortex (PMC), basal ganglia, and dorsolateral prefrontal cortex (DLPFC), among other areas. During synchronise, correlated activity was observed in bilateral SMA, more caudal dorsal and ventral PMC, right DLPFC and right primary motor cortex. No correlated activity was observed during continue at P<0.01 (corrected, cluster level), though left angular gyrus was active at P<0.05. We suggest that the preSMA and rostral dorsal PMC activities during initiate may be associated with selection of timing parameters, while activation in centromedial prefrontal cortex during both initiate and synchronise may be associated with temporal error monitoring or correction. The absence of activity significantly correlated with temporal complexity during continue suggests that, once an overlearned timed movement sequence has been selected and initiated, there is no further adjustment of the timing control processes related to its continued production in absence of external cues.

A recruitment theory of force-time relations in the production of brief force pulses: the parallel force unit model.

A theory, the parallel force unit model, is advanced in which the buildup and decline of force in rapid responses of short duration are assumed to reflect variability in timing of several parallel force units. Response force is conceived of as being a summation of a large number of force units, each acting independently of one another. Force is controlled by either the number of recruited force units or the duration each unit contributes its force. Several predictions are derived on the basis of this theory and are shown to be in qualitative agreement with empirical findings about both the mean and variability of brief force impulses. The model also has consequences for the temporal properties of a response. For example, under certain circumstances, it predicts a reciprocal relation between reaction time and response force. Although the theory is proposed as a psychological account, relations between the assumptions and basic principles in neurophysiology are considered. Possible future applications and generalizations of the theory are discussed.

Effects of sleep deprivation on short duration performance measures compared to the Wilkinson auditory vigilance task.

The effects of one night's total sleep deprivation were examined using the Wilkinson vigilance task and four 10 min duration performance tests. A repeated measures design was used in which eight male subjects experienced one night of sleep loss, the order of sleep loss being balanced across subjects. The four short duration performance tests consisted of choice reaction time, simple reaction time, short-term memory, and a motor task, handwriting. The results confirm the effects of one night's sleep deprivation on the vigilance task and also show that performance on the two reaction time tests was significantly impaired by the loss of sleep, but not at such a high level as for the vigilance. The short-term memory test failed to show any adverse effects of sleep loss and similarly for the handwriting. The experiment shows that two portable and brief (10 min) performance tests are sensitive indices of sleep loss and should be particularly useful for assessing levels of alertness in the field.