The 'problem' with automation: inappropriate feedback and interaction, not 'over-automation'

As automation increasingly takes its place in industry, especially high risk industry, it is often blamed for causing harm and increasing the chance of human error when failures do occur. I propose that the problem is not the presence of automation, but rather its inappropriate design. The problem is that the operations under normal operating conditions are performed appropriately, but there is inadequate feedback and interaction with the humans who must control the overall conduct of the task. When the situations exceed the capabilities of the automatic equipment, then the inadequate feedback leads to difficulties for the human controllers. The problem, I suggest, is that the automation is at an intermediate level of intelligence, powerful enough to take over control that used to be done by people, but not powerful enough to handle all abnormalities. Moreover, its level of intelligence is insufficient to provide the continual, appropriate feedback that occurs naturally among human operators. This is the source of the current difficulties. To solve this problem, the automation should either be made less intelligent or more so, but the current level is quite inappropriate. The overall message is that it is possible to reduce error through appropriate design considerations. Appropriate design should assume the existence of error, it should continually provide feedback, it should continually interact with operators in an effective manner, and it should allow for the worst situations possible. What is needed is a soft, compliant technology, not a rigid, formal one.     

Assigning pathogenicity to mitochondrial tRNA mutations: when "definitely maybe" is not good enough

Some mutations in mitochondrial tRNA (mt-tRNA) genes cause devastating disease, whereas others have no clinical consequences. We understand little of the factors determining the pathogenicity of specific mt-tRNA mutations, making prediction of clinical outcome extremely difficult. Using extensive sequence databases, we compared the characteristics of neutral variations with those of pathogenic mutations. We recommend that the location of the proposed mutation within the secondary structure of the mt-tRNA molecule and the disruption it causes to Watson-Crick base pairing should be considered when assessing the pathological significance of a novel mt-tRNA mutation.     

Sympathetic input modulates, but does not determine, phase of peripheral circadian oscillators

The circadian clock in the suprachiasmatic nucleus (SCN) maintains phase synchrony among circadian oscillators throughout the organism. Environmental light signals entrain the SCN, but timed, limited meal access acts as an overriding time cue for several peripheral tissues. We present data from a peripheral oscillator, the submaxillary salivary gland, in which temporal restriction of meals fails to entrain gene expression. In day-fed rats, submaxillary gland rhythms in expression of the clock gene Period1 (Per1) stay entrained to the light cycle (peaking at night) or become arrhythmic. This result suggests that feeding cues compete weakly with light cycle cues to set the phase of clock genes in this tissue. Since the submaxillary glands receive sympathetic innervation originating in the SCN, which relays light cycle cues to other oscillators, we attempted to assess the role of this neural input in phase control of submaxillary Per1 expression. We sympathetically denervated the submaxillary glands before subjecting rats to daytime-restricted feeding. After denervation, Per1 rhythms in all submaxillary glands shifted phase 180 degrees and entrained to daytime feeding. These results support the hypothesis that peripheral oscillators may receive multiple signals contributing to their phase of entrainment. Sympathetic efferents from the SCN can relay light cycle information, while other external cues may reach tissues through other efferents or nonneural pathways. In an abnormal, disruptive regimen such as daytime-restricted feeding, these different signals compete. Arrhythmicity may result if one signal is not clearly dominant. Elimination of the dominant signal (e.g., surgical sympathectomy) may allow a secondary signal to control phase.     

Difficult phylogenetic questions: more data, maybe; better methods, certainly

The combination of molecular sequence data and bioinformatics has revolutionized phylogenetic inference over the past decade, vastly increasing the scope of the evolutionary trees that we are able to infer. A recent paper in BMC Biology describing a new phylogenomic pipeline to help automate the inference of evolutionary trees from public sequence databases provides another important tool in our efforts to derive the Tree of Life. See research article: http://www.biomedcentral.com/1741-7007/9/55     

Location, location, location..

Intra-abdominal fat is an established risk factor for the metabolic syndrome. In this issue of Cell Metabolism, Tran et al. (2008) test the cell-autonomous and location-related properties of transplanted intra-abdominal and subcutaneous fat depots. While subcutaneous fat seems to confer metabolic benefits, species differences in adipose biology justify caution in interpreting the results.     

安全第一

人们通常都关注胚胎干细胞研究中的伦理道德问题,而忽略了再生医学中使用这些细胞时的实际困难。2006年,Yamanaka和他的同事们报告了完全用体细胞诱导形成的多能干细胞（iPSCs）与胚胎干细胞在功能上的相似性。这个重大突破为解决使用人类胚胎的争议提供了一种新的可能,同时也让病人可以得到来自于自身的干细胞,从而减少了排异反应。     

Multiple neural oscillators and muscle feedback are required for the intestinal fed state motor program

After a meal, the gastrointestinal tract exhibits a set of behaviours known as the fed state. A major feature of the fed state is a little understood motor pattern known as segmentation, which is essential for digestion and nutrient absorption. Segmentation manifests as rhythmic local constrictions that do not propagate along the intestine. In guinea-pig jejunum in vitro segmentation constrictions occur in short bursts together with other motor patterns in episodes of activity lasting 40-60 s and separated by quiescent episodes lasting 40-200 s. This activity is induced by luminal nutrients and abolished by blocking activity in the enteric nervous system (ENS). We investigated the enteric circuits that regulate segmentation focusing on a central feature of the ENS: a recurrent excitatory network of intrinsic sensory neurons (ISNs) which are characterized by prolonged after-hyperpolarizing potentials (AHPs) following their action potentials. We first examined the effects of depressing AHPs with blockers of the underlying channels (TRAM-34 and clotrimazole) on motor patterns induced in guinea-pig jejunum, in vitro, by luminal decanoic acid. Contractile episode durations increased markedly, but the frequency and number of constrictions within segmenting bursts and quiescent period durations were unaffected. We used these observations to develop a computational model of activity in ISNs, excitatory and inhibitory motor neurons and the muscle. The model predicted that: i) feedback to ISNs from contractions in the circular muscle is required to produce alternating activity and quiescence with the right durations; ii) transmission from ISNs to excitatory motor neurons is via fast excitatory synaptic potentials (EPSPs) and to inhibitory motor neurons via slow EPSPs. We conclude that two rhythm generators regulate segmentation: one drives contractions within segmentation bursts, the other the occurrence of bursts. The latter depends on AHPs in ISNs and feedback to these neurons from contraction of the circular muscle.