Science 22 February 2008: Vol. 319. no. 5866, pp. 1022 - 1023
Once Shunned, Test for Alzheimer's Risk Headed to Market
A Pennsylvania company is preparing to market a genetic test that will tell healthy people whether they are
at risk for developing Alzheimer’s disease. It is getting a mixed response from researchers.

Science 22 February 2008: Vol. 319. no. 5866, pp. 1086 - 1089
Differential Regulation of Dynein and Kinesin Motor Proteins by Tau
Dynein and kinesin motor proteins transport cellular cargoes toward opposite ends of microtubule tracks.
In neurons, microtubules are abundantly decorated with microtubule-associated proteins (MAPs) such as tau. Motor proteins thus encounter MAPs frequently along their path. To determine the effects of tau on dynein and kinesin motility, we conducted single-molecule studies of motor proteins moving along tau-decorated microtubules. Dynein tended to reverse direction, whereas kinesin tended to detach at patches of bound tau. Kinesin was inhibited at about a tenth of the tau concentration that inhibited dynein, and the microtubule-binding domain of tau was sufficient to inhibit motor activity. The differential modulation of dynein and kinesin motility suggests that MAPs can spatially regulate the balance of microtubule-dependent axonal transport.

Science 22 February 2008: Vol. 319. no. 5866, pp. 1104 - 1107
Spine-Type-Specific Recruitment of Newly Synthesized AMPA Receptors with Learning
The stabilization of long-term memories requires de novo protein synthesis. How can proteins, synthesized
in the soma, act on specific synapses that participate in a given memory? We studied the dynamics of newly synthesized AMPA-type glutamate receptors (AMPARs) induced with learning using transgenic mice expressing the GluR1 subunit fused to green fluorescent protein (GFP-GluR1) under control of the c-fos promoter. We found learning-associated recruitment of newly synthesized GFP-GluR1 selectively to mushroom-type spines in adult hippocampal CA1 neurons 24 hours after fear conditioning.
Our results are consistent with a "synaptic tagging" model to allow activated synapses to subsequently capture newly synthesized receptor and also demonstrate a critical functional distinction in the mushroom spines with learning.

Science 22 February 2008: Vol. 319. no. 5866, pp. 1108 - 1111
Rapid Neural Coding in the Retina with Relative Spike Latencies
Natural vision is a highly dynamic process. Frequent body, head, and eye movements constantly bring new images onto the retina for brief periods, challenging our understanding of the neural code for vision.
We report that certain retinal ganglion cells encode the spatial structure of a briefly presented image in the relative timing of their first spikes. This code is found to be largely invariant to stimulus contrast and robust to noisy fluctuations in response latencies. Mechanistically, the observed response characteristics result from different kinetics in two retinal pathways ("ON" and "OFF") that converge onto ganglion cells. This mechanism allows the retina to rapidly and reliably transmit new spatial information with the very first spikes emitted by
a neural population.

Science 22 February 2008: Vol. 319. no. 5866, pp. 1111 - 1113
Predicting Human Interactive Learning by Regret-Driven Neural Networks
Much of human learning in a social context has an interactive nature: What an individual learns is affected by what other individuals are learning at the same time. Games represent a widely accepted paradigm for representing interactive decision-making. We explored the potential value of neural networks for modeling and predicting human interactive learning in repeated games. We found that even very simple learning networks, driven by regret-based feedback, accurately predict observed human behavior in different experiments on 21 games with unique equilibria in mixed strategies. Introducing regret in the feedback dramatically improved the performance of the neural network. We show that regret-based models provide better predictions of learning than established economic models.

Science 22 February 2008: Vol. 319. no. 5866, p. 1028
AAAS ANNUAL MEETING: How Human Intelligence Evolved--Is It Science or 'Paleofantasy'?
BOSTON, MASSACHUSETTS--At the AAAS annual meeting here from February 14 to 18, a panel of top researchers discussed what, if anything, scientists have learned about the evolution of human intelligence.

Science 22 February 2008: Vol. 319. no. 5866, pp. 1028 - 1029
AAAS ANNUAL MEETING: Tracking and Tackling Deprivation's Toll
BOSTON, MASSACHUSETTS--At the AAAS annual meeting here from February 14 to 18, psychologists presented a new study aimed at showing how poverty affects children's memory and language skills, and others suggested a partial remedy.

BMJ  2008;336:337-338 (16 February), doi:10.1136/bmj.39456.470880.80 (published 29 January 2008)
Functional status and long term outcome of stroke Despite undoubted progress, we still have much to do
Despite advances in prevention, acute care, and rehabilitation the prognosis after acute stroke remains poor: 20-30% of patients die within a month and 13% of survivors are discharged to institutional care. In the accompanying prospective cohort study, Bruin Slot and colleagues report that functional status at six months after stroke is associated with long term survival. The median survival of patients who were independent at this stage was 9.7 years compared with 6.0 years for those who were dependent. The effect of functional outcome at six months on mortality was independent of age and stroke subtype. The study gives no details about the causes of death or whether secondary prevention was optimised, but these survival data again emphasise the impact of stroke. They also suggest that early treatment known to reduce dependency at six months may have a substantial longer term effect.

THE EARLY ACCOUNTS OF EPIDEMIC POLIOMYELITIS.
The early accounts which tend to establish any particular disease as a definite clinical entity naturally have a peculiar interest to all who find pleJAMA. 2008;299(7):843. February 29, 1908asure in tracing the development of medical knowledge. The recent epidemics of poliomyelitis, especially in Norway, and during the past few months in various parts of this country also, have directed attention to the historical side of this disease, which no doubt occurred in the past in about the same way as it is manifesting itself in these days. At first, Bergenholtz, in Finland, was thought to have been the first to describe an epidemic of poliomyelitis, at least in Europe, his report covering 18 cases. Then it was found1 that the disease had been clearly described in 1868 by A. C. Bull, a country physician in Norway, under the title of "Meningitis Spinalis Acuta."

The Lancet, Volume 371, Issue 9612, 16 February 2008-22 February 2008, Pages 597-607
Management of acute organophosphorus pesticide poisoning
Organophosphorus pesticide self-poisoning is an important clinical problem in rural regions of the developing world, and kills an estimated 200 000 people every year. Unintentional poisoning kills far fewer people but is a problem in places where highly toxic organophosphorus pesticides are available. Medical management is difficult, with case fatality generally more than 15%. We describe the limited evidence that
can guide therapy and the factors that should be considered when designing further clinical studies.
50 years after first use, we still do not know how the core treatments—atropine, oximes,
and diazepam—should best be given. Important constraints in the collection of useful data have included the late recognition of great variability in activity and action of the individual pesticides, and the care needed cholinesterase assays for results to be comparable between studies. However, consensus suggests that early resuscitation with atropine, oxygen, respiratory support, and fluids is needed to improve oxygen delivery to tissues.
The role of oximes is not completely clear; they might benefit only patients poisoned by specific pesticides or patients with moderate poisoning. Small studies suggest benefit from new treatments such as magnesium sulphate, but much larger trials are needed. Gastric lavage could have a role but should only be undertaken once the patient is stable. Randomised controlled trials are underway in rural Asia to assess the effectiveness of these therapies. However, some organophosphorus pesticides might prove very difficult to treat with current therapies, such that bans on particular pesticides could be the only method to substantially reduce the case fatality after poisoning. Improved medical management of organophosphorus poisoning should result in
a reduction in worldwide deaths from suicide.

Volume 358:794-810  February 21, 2008  Number 8
 Surgical versus Nonsurgical Therapy for Lumbar Spinal Stenosis
Background Surgery for spinal stenosis is widely performed, but its effectiveness as compared with nonsurgical treatment has not been shown in controlled trials.
Methods Surgical candidates with a history of at least 12 weeks of symptoms and spinal stenosis without spondylolisthesis (as confirmed on imaging) were enrolled in either a randomized cohort or an observational cohort at 13 U.S. spine clinics. Treatment was decompressive surgery or usual nonsurgical care.
The primary outcomes were measures of bodily pain and physical function on the Medical Outcomes Study 36-item Short-Form General Health Survey (SF-36) and the modified Oswestry Disability Index at 6 weeks,
3 months,
6 months, and 1 and 2 years.
Results A total of 289 patients were enrolled in the randomized cohort, and 365 patients were enrolled in the observational cohort. At 2 years, 67% of patients who were randomly assigned to surgery had undergone surgery, whereas 43% of those who were randomly assigned to receive nonsurgical care had also undergone surgery. Despite the high level of nonadherence, the intention-to-treat analysis of the randomized cohort showed a significant treatment effect favoring surgery on the SF-36 scale for bodily pain, with a mean difference in change from baseline of 7.8 (95% confidence interval, 1.5 to 14.1); however, there was no significant difference in scores on physical function or on the Oswestry Disability Index. The as-treated analysis, which combined both cohorts and was adjusted for potential confounders, showed a significant advantage for surgery by 3 months for all primary outcomes; these changes remained significant at 2 years.
Conclusions In the combined as-treated analysis, patients who underwent surgery showed significantly more improvement in all primary outcomes than did patients who were treated nonsurgically.
(ClinicalTrials.gov number, NCT00000411 [ClinicalTrials.gov] .)

Volume 358:818-825  February 21, 2008  Number 8
Lumbar Spinal Stenosis
This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist.
The article ends with the authors' clinical recommendations. A 72-year-old woman with hypertension presents with a 4-month history of lower back discomfort that radiates to both buttocks and lateral thighs. Previously, she had walked 2 miles (3.2 km) a day; now she has difficulty walking 2 blocks and standing up for more than 15 minutes at a time. Her physical examination is notable only for a slightly stooped posture and a reduction of vibratory sensibility in both great toes. How should she be evaluated and treated?

Volume 358:853-855  February 21, 2008  Number 8
Incidental Findings on Brain MRI
To the Editor: Vernooij et al. (Nov. 1 issue)1 have contributed valuable knowledge about the prevalence
of asymptomatic intracranial lesions. However, we disagree with their statement that many incidental lesions
do not merit further evaluation or treatment.
The authors cite results of the International Study of Unruptured Intracranial Aneurysms (ISUIA) to justify not further evaluating small aneurysms, but conventional magnetic resonance sequences used in this study are unreliable in characterizing aneurysms. Digital subtraction angiography or computed tomographic
or magnetic resonance angiography is a superior diagnostic technique. Furthermore, a significant proportion of subarachnoid hemorrhages result from small aneurysms, mandating careful risk assessment based
on individual factors.

Volume 358:855-856  February 21, 2008  Number 8
Visualizing Out-of-Body Experience in the Brain
To the Editor: The single-subject study design used by De Ridder et al. (Nov. 1 issue)1 makes it difficult to conclude whether the changes seen on positron-emission tomography (PET) were due to out-of-body experiences or simply to the differential effects of stimulation at 3.7 V in 40-Hz burst mode as compared with other modes, a confounder that has not been controlled for. A more robust approach would be to compare this patient with a group of patients with tinnitus, but without the out-of-body experiences, receiving the same stimulation.