In a cluster-randomized trial conducted in five ICUs, a nurse-led family-support intervention did not affect surrogates’ scores for anxiety and depression 6 months after the patients’ ...hospitalization, but it improved surrogates’ ratings of the patient-centeredness of care.
Summary Background Paralysis or amputation of an arm results in the loss of the ability to orient the hand and grasp, manipulate, and carry objects, functions that are essential for activities of ...daily living. Brain–machine interfaces could provide a solution to restoring many of these lost functions. We therefore tested whether an individual with tetraplegia could rapidly achieve neurological control of a high-performance prosthetic limb using this type of an interface. Methods We implanted two 96-channel intracortical microelectrodes in the motor cortex of a 52-year-old individual with tetraplegia. Brain–machine-interface training was done for 13 weeks with the goal of controlling an anthropomorphic prosthetic limb with seven degrees of freedom (three-dimensional translation, three-dimensional orientation, one-dimensional grasping). The participant's ability to control the prosthetic limb was assessed with clinical measures of upper limb function. This study is registered with ClinicalTrials.gov , NCT01364480. Findings The participant was able to move the prosthetic limb freely in the three-dimensional workspace on the second day of training. After 13 weeks, robust seven-dimensional movements were performed routinely. Mean success rate on target-based reaching tasks was 91·6% (SD 4·4) versus median chance level 6·2% (95% CI 2·0–15·3). Improvements were seen in completion time (decreased from a mean of 148 s SD 60 to 112 s 6) and path efficiency (increased from 0·30 0·04 to 0·38 0·02). The participant was also able to use the prosthetic limb to do skilful and coordinated reach and grasp movements that resulted in clinically significant gains in tests of upper limb function. No adverse events were reported. Interpretation With continued development of neuroprosthetic limbs, individuals with long-term paralysis could recover the natural and intuitive command signals for hand placement, orientation, and reaching, allowing them to perform activities of daily living. Funding Defense Advanced Research Projects Agency, National Institutes of Health, Department of Veterans Affairs, and UPMC Rehabilitation Institute.
Why are
Homo sapiens
the only human species living on this planet?
Homo sapiens
have lived on this planet for about 300,000 years. During most of their existence, early modern humans shared this ...planet with other archaic humans, such as Neanderthals and Denisovans. Why did the other archaic humans become extinct? To explore this question, this study develops a Malthusian model with natural selection of human species to explore how population dynamics of one group of humans may cause the extinction of another group. In my model, different groups of humans engage in hunting-gathering. The larger group of humans can occupy more land. Therefore, the expansion of one population causes the other population to shrink in a Malthusian economy. Which human population shrinks or even becomes extinct depends on structural parameters in the Malthusian model.
The ubiquitous serine/threonine protein phosphatase 1 (PP1) regulates diverse, essential cellular processes such as cell cycle progression, protein synthesis, muscle contraction, carbohydrate ...metabolism, transcription and neuronal signaling. However, the free catalytic subunit of PP1, while an effective enzyme, lacks substrate specificity. Instead, it depends on a diverse set of regulatory proteins (≥ 200) to confer specificity towards distinct substrates. Here, we discuss recent advances in structural studies of PP1 holoenzyme complexes and summarize the new insights these studies have provided into the molecular basis of PP1 regulation and specificity.
Protein Phosphatase 1 (PP1) regulates diverse, essential cellular processes such as cell cycle progression, protein synthesis, muscle contraction, carbohydrate metabolism, transcription and neuronal signaling. We review recent advances in structural studies of PP1 holoenzyme complexes and summarize the new insights these studies have provided into the molecular basis of PP1 regulation and specificity.
Differentiating acute bacterial infection from other causes of lower respiratory tract illness is challenging. In this trial, procalcitonin was investigated as a point-of-care test to aid in ...determining whether antibiotics were needed in the treatment of these illnesses.
Reducing the global burden of sepsis, a recognized global health challenge, requires comprehensive data on the incidence and mortality on a global scale.
To estimate the worldwide incidence and ...mortality of sepsis and identify knowledge gaps based on available evidence from observational studies.
We systematically searched 15 international citation databases for population-level estimates of sepsis incidence rates and fatality in adult populations using consensus criteria and published in the last 36 years.
The search yielded 1,553 reports from 1979 to 2015, of which 45 met our criteria. A total of 27 studies from seven high-income countries provided data for metaanalysis. For these countries, the population incidence rate was 288 (95% confidence interval CI, 215-386; τ = 0.55) for hospital-treated sepsis cases and 148 (95% CI, 98-226; τ = 0.99) for hospital-treated severe sepsis cases per 100,000 person-years. Restricted to the last decade, the incidence rate was 437 (95% CI, 334-571; τ = 0.38) for sepsis and 270 (95% CI, 176-412; τ = 0.60) for severe sepsis cases per 100,000 person-years. Hospital mortality was 17% for sepsis and 26% for severe sepsis during this period. There were no population-level sepsis incidence estimates from lower-income countries, which limits the prediction of global cases and deaths. However, a tentative extrapolation from high-income country data suggests global estimates of 31.5 million sepsis and 19.4 million severe sepsis cases, with potentially 5.3 million deaths annually.
Population-level epidemiologic data for sepsis are scarce and nonexistent for low- and middle-income countries. Our analyses underline the urgent need to implement global strategies to measure sepsis morbidity and mortality, particularly in low- and middle-income countries.
A signature trait of neurotropic α-herpesviruses (α-HV) is their ability to establish stable non-productive infections of peripheral neurons termed latency. This specialized gene expression program ...is the foundation of an evolutionarily successful strategy to ensure lifelong persistence in the host. Various physiological stresses can induce reactivation in a subset of latently-infected neurons allowing a new cycle of viral productive cycle gene expression and synthesis of infectious virus. Recurring reactivation events ensure transmission of the virus to new hosts and contributes to pathogenesis. Efforts to define the molecular basis of α-HV latency and reactivation have been notoriously difficult because the neurons harboring latent virus in humans and in experimentally infected live-animal models, are rare and largely inaccessible to study. Increasingly, researchers are turning to cultured neuron infection models as simpler experimental platforms from which to explore latency and reactivation at the molecular level. In this review, I reflect on the strengths and weaknesses of existing neuronal models and briefly summarize the important mechanistic insights these models have provided. I also discuss areas where prioritization will help to ensure continued progress and integration.
Before the invention of electric lighting, humans were primarily exposed to intense (>300 lux) or dim (<30 lux) environmental light—stimuli at extreme ends of the circadian system’s dose–response ...curve to light. Today, humans spend hours per day exposed to intermediate light intensities (30–300 lux), particularly in the evening. Interindividual differences in sensitivity to evening light in this intensity range could therefore represent a source of vulnerability to circadian disruption by modern lighting. We characterized individual-level dose–response curves to light-induced melatonin suppression using a within-subjects protocol. Fifty-five participants (aged 18–30) were exposed to a dim control (<1 lux) and a range of experimental light levels (10–2,000 lux for 5 h) in the evening. Melatonin suppression was determined for each light level, and the effective dose for 50% suppression (ED50) was computed at individual and group levels. The group-level fitted ED50 was 24.60 lux, indicating that the circadian system is highly sensitive to evening light at typical indoor levels. Light intensities of 10, 30, and 50 lux resulted in later apparent melatonin onsets by 22, 77, and 109 min, respectively. Individual-level ED50 values ranged by over an order of magnitude (6 lux in the most sensitive individual, 350 lux in the least sensitive individual), with a 26% coefficient of variation. These findings demonstrate that the same evening-light environment is registered by the circadian system very differently between individuals. This interindividual variability may be an important factor for determining the circadian clock’s role in human health and disease.
Context:
Late adolescence is marked by a delay in sleep timing, which is partly driven by a delay shift of the circadian timing system. This study examined whether the sensitivity of the circadian ...system to light—the primary entraining stimulus to the circadian system—differs between pre- to mid-pubertal and late to postpubertal adolescents.
Objective:
The study was designed to determine the influence of puberty on the sensitivity of the circadian system to light in humans.
Methods:
Melatonin suppression to low and moderate light levels was assessed in 38 pre- to mid-pubertal (9.1–14.7 years) and 29 late to postpubertal (11.5–15.9 years) adolescents. They received 1 hour of four light levels on consecutive nights: approximately 0.1 (near-dark baseline condition), 15, 150, and 500 lux. One group received evening light beginning at 11:00 pm (n = 39); a second group received morning light beginning at 3:00 am (n = 28). Salivary melatonin was sampled every 30 minutes. Melatonin suppression for 15, 150, and 500 lux was calculated relative to unsuppressed baseline levels in the 0.1 lux setting, within individuals.
Results:
The pre- to mid-pubertal group showed significantly greater melatonin suppression to 15 lux (9.2 ± 20.5%), 150 lux (26.0 ± 17.7%), and 500 lux (36.9 ± 11.4%) during evening light exposure compared to the late to postpubertal group (−5.3 ± 17.7%, 12.5 ± 17.3%, and 23.9 ± 21.7%, respectively; P < .05). No significant differences were seen between developmental groups in morning melatonin suppression.
Conclusion:
These results indicate support for a greater sensitivity to evening light in early pubertal children. The increased sensitivity to light in younger adolescents suggests that exposure to evening light could be particularly disruptive to sleep regulation for this group.
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