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Köhler et al. (2018, https://doi.org/10.1002/2017JF004375) deploy a high spatial and temporal resolution GEODAR radar system to reveal the inside of snow avalanches over the entire slope. They detect a rich variety of longitudinal and slope normal flow structures across a data set of 77 avalanches recorded over 6 years. Distinctive features in the radar signatures permit the definition of seven flow regimes and three distinct stopping signatures, illustrating behaviors much richer than the conventional dichotomy between dense flow avalanches and powder snow avalanches. This presents modelers with the challenge of exploring the physics of these regimes, the transitions between them and their relationship with the surrounding conditions. Köhler et al. (2018) deploy a high spatial and temporal resolution GEODAR radar system to reveal the inside of snow avalanchesThey detect a rich variety of longitudinal and slope normal flow structures across a data set of 77 avalanchesDistinctive radar signatures permit the definition of seven flow regimes and three stopping signatures which are challenging for modelers

Complete immunosuppressive drug withdrawal without subsequent rejection was accomplished in fully HLA‐matched kidney transplant patients with persistent mixed chimerism, and withdrawal is now being studied in HLA haplotype‐matched patients with persistent mixed chimerism. See editorial by Thornley and Strom on page 583.

The integrin αvβ6 activates latent transforming growth factor-β (TGF-β) within the kidney and may be a target for the prevention of chronic allograft fibrosis after kidney transplantation. However, TGF-β also has known immunosuppressive properties that are exploited by calcineurin inhibitors (CNIs); thus, the net benefit of αvβ6 inhibition remains undetermined. To assess the acute impact of interference with αvβ6 on acute rejection, we tested a humanized αvβ6-specific monoclonal antibody (STX-100) in a randomized, double-blinded, placebo-controlled nonhuman primate renal transplantation study to evaluate whether αvβ6 blockade alters the risk of acute rejection during CNI-based immunosuppression. Rhesus monkeys underwent renal allotransplantation under standard CNI-based maintenance immunosuppression; 10 biopsy-confirmed rejection-free animals were randomized to receive weekly STX-100 or placebo. Animals treated with STX-100 experienced significantly decreased rejection-free survival compared to placebo animals (p = 0.049). Immunohistochemical analysis confirmed αvβ6 ligand presence, and αvβ6 staining intensity was lower in STX-100-treated animals (p = 0.055), indicating an apparent blockade effect of STX-100. LAP, LTBP-1 and TGF-β were all decreased in animals that rejected on STX-100 compared to those that rejected on standard immunosuppression alone, suggesting a relevant effect of αvβ6 blockade on local TGF-β. These data caution against the use of αvβ6 blockade to achieve TGF-β inhibition in kidney transplantation.

The authors report on the use of an αvβ6 monoclonal antibody and its association with acute rejection when used in concert with calcineurin inhibitor–based immunosuppression in a nonhuman primate renal transplant model.

To estimate the incidence rate (IR) of progressive multifocal leukoencephalopathy (PML) in patients without HIV.

This work uses a one-dimensional, depth averaged model to compute the massbalance of a mixed flowing/powder snow avalanche. This model is comprisedof three basic components: the dense flowing avalanche, the powder cloud anda turbulent wake. The dynamics of a mixed avalanche is strongly dependent onthe interaction between the components and also on the snow cover and ambientair, in particular the exchange or entrainment of snow and air mass. Therefore, animportant first step for modelling mixed avalanches is a basic understanding of thenature of these mass exchanges. In this paper, the governing equations of mass,momentum and turbulent energy are briefly presented. Numerical simulations wererun for three avalanche tracks – Aulta, Galtür and Vallée de la Sionne – for whichdata from real snow avalanche events exist. Based on the results, conclusions weredrawn regarding the parameterisation of the mass exchanges. The mass balances forthese three contrasting avalanches are presented.

The linear mixed model is a well‐known method for incorporating heterogeneity (for example, subject‐to‐subject variation) into a statistical analysis for continuous responses. However heterogeneity cannot always be fully captured by the usual assumptions of normally distributed random effects. Latent class mixed models offer a way of incorporating additional heterogeneity which can be used to uncover distinct subpopulations, to incorporate correlated non‐normally distributed outcomes and to classify individuals. The methodology is motivated with examples in health care studies and a detailed illustration is drawn from the Nutritional Prevention of Cancer trials. Latent class models are used with longitudinal data on prostate specific antigen (PSA) as well as incidence of prostate cancer. The models are extended to accommodate prostate cancer as a survival endpoint; this is compared to treating it as a binary endpoint. Four subpopulations are identified which differ both with regard to their PSA trajectories and their incidence rates of prostate cancer. Copyright © 2002 John Wiley & Sons, Ltd.

The linear mixed model is a well-known method for incorporating heterogeneity (for example, subject-to-subject variation) into a statistical analysis for continuous responses. However heterogeneity cannot always be fully captured by the usual assumptions of normally distributed random effects. Latent class mixed models offer a way of incorporating additional heterogeneity which can be used to uncover distinct subpopulations, to incorporate correlated non-normally distributed outcomes and to classify individuals. The methodology is motivated with examples in health care studies and a detailed illustration is drawn from the Nutritional Prevention of Cancer trials. Latent class models are used with longitudinal data on prostate specific antigen (PSA) as well as incidence of prostate cancer. The models are extended to accommodate prostate cancer as a survival endpoint; this is compared to treating it as a binary endpoint. Four subpopulations are identified which differ both with regard to their PSA trajectories and their incidence rates of prostate cancer. Copyright © 2002 John Wiley & Sons, Ltd.

A new disease, angiomatosis, was recognized in 25 of 54 (46.3%) Atlantic bottlenose dolphins (Tursiops truncatus) necropsied after being stranded along the Texas Gulf coast during 1991-1996. Angiomatosis was first recognized by the authors in 1992 and has increased in incidence and severity, affecting 100% of juveniles and adults. This disease is characterized by proliferation of small, thick-walled blood vessels diffusely throughout the lungs, without inflammation, exudation, or alveolar hemorrhage. The vascular proliferation also occurs in lung-associated and other visceral lymph nodes. Hemangiomas frequently occur in affected lymph nodes and occasionally in the lungs. The vascular proliferation reduces airspace and may occlude small airways. Angiomatosis appears to be a broad-field defect of vascular endothelium. Although this process appears to be an increasingly important factor in the morbidity of T. truncatus, its etiology has not been determined.

The immediate effects of total or partial denervation of single digits (0-16 hr after nerve transection) on primary somatosensory cortex were studied electrophysiologically. Comparisons of response properties and cortical somatotopy were made between intact raccoons and four groups of raccoons with transection of some or all of the nerves innervating the fourth or fifth digit. Animals with all four digital nerves cut (amputation of the digit) were most different from normal. Approximately half of the penetrations in the affected cortical region showed inhibitory responses to stimulation of adjacent skin regions. These consisted of a strong response to stimulus offset and/or a suppression of spontaneous activity during indentation. Since these responses were substantially different from those recorded several months after digit amputation, additional changes in connectivity and synaptic strength must occur with chronic denervation. These inhibitory responses were not seen in animals with one, two, or three nerves cut per digit.In the animals with partial denervation of a digit, the greatest disruption occurred when both ventral nerves to the glabrous skin were transected. This yielded cell clusters with abnormally large receptive fields, disruptions in somatotopic organization, and a decreased occurrence of low-threshold responses. If only one nerve to glabrous skin was transected, there was less change, even if it was combined with transection of both nerves to hairy skin. These results suggest that the release of inhibitory responses in a cortical digital region by amputation is prevented by the retention of even one ventral nerve. None of the denervation conditions produced large nonresponsive areas of cortex, which would have indicated a loss of all inputs.

Physiological recordings were made from 136 slowly adapting (SA) fibers in the median and ulnar nerves that innervate the glabrous skin of the raccoon. It was found that wetting the skin produced large increases in fiber responsiveness and decreases in threshold. Their responses decreased rapidly with slight displacements of the stimulus away from the center of the receptive field. Responses also decreased with increases in the diameter of the tip of the stimulus probe. The length of time that an SA fiber responded to a prolonged indentation was related to the magnitude of the indentation, and was greater after wetting of the skin. The absence of any clear and consistent grouping of fibers into moderately SA (MSA) and very SA (VSA) units argues against the existence of two types of SA receptors differing in this property. However, the distinction between SA I and SA II fibers that has been made in other species was confirmed in the raccoon.

Electrophysiological recordings were made from the median, ulnar, radial, and dorsal ulnar nerves to determine the types of mechanosensory receptors serving glabrous and hairy skin surfaces of the raccoon forepaw. In addition to the cutaneous mechanoreceptors, fibers innervating deep tissues were also recorded from each of these nerves. These included sensory fibers innervating muscles, joints, claws, and the subcutaneous pulp.The array of receptors serving raccoon glabrous skin was the same as found in monkeys and humans: Rapidly adapting (RA), slowly adapting (SA), and Pacinian (Pc) fibers were characterized. Pacinian fibers have been rarely described in previous physiological studies of the raccoon peripheral nerves, but in the present study they composed between 14% and 18% of the glabrous skin mechanoreceptors recorded. A distal-proximal gradient in the density of skin innervation was evident for all three types of receptors.Receptors characterized in the hairy skin of the dorsal paw were similar to those described in other mammals, and included both down and guard hair afferents, non-hair-associated RA fibers, and SA I and SA II fibers. The relative proportions of these fibers differed from those generally reported for the hairy skin of other mammals. SA hair-associated afferent fibers, which have been reported previously only in primate hairy skin, were also found in large numbers in the raccoon. Similarities and differences in the frequency and types of receptors innervating the raccoon forepaw, the forepaws of other mammals, and the hands of primates (including humans) are discussed.

1. Influence of temperature on electrically evoked twitch contractions and maximal voluntary contractions was studied in human first dorsal interosseus muscle. The range of the muscle temperature was 35‐12 degrees C. 2. The maximal twitch tension decreased by about 50% in cooling from 35‐12 degrees C; the tension decrease was more pronounced below 25 degrees C. The temperature coefficients (Q10 values) estimated for muscle temperatures of 35‐25 degrees C were 1.43 for time‐to‐peak and 1.7 for half‐time of relaxation. 3. The maximum voluntary tension remained relatively constant on cooling to 25 degrees C but decreased by about 30% on cooling to 12‐15 degrees C. The normalized rate of tension rise in voluntary contractions was largely independent of temperature. 4. Results are discussed in relation to previous work on temperature and muscle contraction in humans and in animals.

In nine adult baboons, full‐thickness skin grafts were reciprocally exchanged between three glabrous skin sites on one hand and glabrous skin sites on the contralateral hand or foot, and a hairy skin site on the dorsum of the ipsilateral hand. The grafts acquired some of the physical characteristics of the recipient site; glabrous skin became thinner and more pliable on the dorsum of the hand and hairy skin became thicker and displayed a more irregular surface contour when transferred to the palm. The electrophysiological properties of cutaneous mechanoreceptors serving these grafts were examined about 5 months after surgery and again after 1 year. Measurements of conduction velocity, receptive field size and shape, and responses to mechanical stimuli suggested that axons serving mechanoreceptors in glabrous grafts functioned at nearly normal levels by 5 months, while axons innervating hairy skin grafts, whether transferred to a glabrous skin site or to a hairy skin site, performed less well even after 1 year. These observations suggest that factors intrinsic to the graft are a major determinant of the quality of sensory function achieved following a skin graft procedure. These factors affect the relative proportions of rapidly and slowly adapting fibres, conduction velocities, thresholds and receptive field configurations. As a result, hairy skin is not the tissue choice for plastic surgical procedures requiring optimum sensory return.

The authors propose a procedure for the detection of significant clusters of chronic diseases, with particular reference to cancer. The procedure allows for variations in population density and avoids the problem of "post hoc" formation of hypotheses or self-defined populations. This accounts for several of the principal problems of cluster evaluations. The techniques are practical but "computer-intensive." The procedure, termed the "cluster evaluation permutation procedure," is applied to leukemia incidence data for an Upstate New York region obtained from the New York State Cancer Registry and census files. Comparisons are made with two other recently proposed clustering methods, namely the U-statistic method of Whittemore et al. (Biometrika 1987;74:631-7) and the "geographical analysis machine" of Openshaw et al. (Lancet 1988;1:272-3). Routine examination of disease occurrence with the cluster evaluation permutation procedure would allow state health officials to prioritize case investigations and to respond in a timely and efficient manner to inquiries of reported clusters.

Electrophysiological recordings were made in the primary somatosensory cortex of anesthetized raccoons 14 to 169 days following digit amputation or 60 to 129 days after transection of the two nerves innervating the ventral surface of the fourth digit. The incidence of inhibitory responses decreased from 50% of the penetrations immediately after amputation to 35% over the first 3 weeks and to almost zero after 2 months. The number of sites with low-threshold excitatory responses increased from 4% to 14% to 50% during these same intervals. Initially, the excitatory fields were small and located over the nerve stumps, and were therefore probably due to direct stimulation of the damaged nerves. At 2 months after amputation, the excitatory receptive fields were large and diffuse. Although the size of receptive fields decreased during the later period (when the thresholds were also decreasing), there was no recovery of any precise somatotopic organization in the deafferented cortex. The reorganization process in the raccoon thus consists of at least two stages: The early stage is dominated by inhibitory connections, whereas the second involves a recovery and restructuring of excitatory inputs.From 2 to 4 months after partial digit denervation, there were only minor changes in response properties or somatotopic organization in the deafferented cortex as compared to immediately after nerve transection. Thus, few of the characteristics of reorganization induced by digit amputation were elicited by this treatment, which leaves some of the digit innervation intact. There was, however, an unexpected increase in the portion of the ventral digit that was able to activate the cortex, suggesting complexities in the peripheral innervation of the digit that need to be resolved.

This report summarizes single-fiber and multifiber data from the median, ulnar, dorsal ulnar, and superficial radial nerves innervating the raccoon forepaw with respect to the cutaneous domains innervated by each nerve. The median nerve was found to innervate the ventral surface of the first four digits and the radial two-thirds of the palm. Its innervation extended onto digit 5 in some animals. The palmar branch of the ulnar nerve innervated digits 4 and 5 and the ulnar half of the palm. The superficial radial nerve innervated the dorsal surface of the first four digits and the radial two-thirds of the forepaw, whereas the dorsal branch of the ulnar nerve innervated the ulnar half of the paw and digits 4 and 5. Overlap of adjacent nerves was verified in several cases by recording from two nerves in the same animal. The domains of the ventral and dorsal nerves overlapped at the borders of glabrous and hairy skin, particularly around the claws.Fiber types were not strictly grouped within particular fascicles according to either spatial or functional characteristics. However, there was a tendency toward overrepresentation of different modality and submodality types in different fascicles. The relevance of the overlap zones and autonomous zones of these nerves to experiments on central effects of peripheral nerve injury is discussed.

Based on health insurance claims from a large U.S. health insurer, the authors identified 44 progressive multifocal leukoencephalopathy (PML) cases from 2002 through 2004 and described their characteristics, including antecedent diagnoses and treatments as well as survival. Immunosuppressive conditions such as HIV/AIDS, rather than potentially immunosuppressive treatments, were the main antecedents of PML. A lower mortality was observed among PML patients whose antecedent diagnosis was HIV/AIDS, the majority of whom received highly active antiretroviral therapy.