Thunderstorm asthma: a review, risks for Aotearoa New Zealand, and health emergency management considerations.

AIM: To provide an up-to-date review of thunderstorm asthma (TA), identifying causative factors, and to discuss implications for management of TA in New Zealand. METHODS: A literature search was carried out to identify articles that investigate the characteristics and causative factors of TA. Nine electronic databases were searched, yielding 372 articles, reduced to 30 articles after screening for duplication and relevance. RESULTS: TA is globally rare, with 29 reported events since 1983, but is expected to increase in frequency as Earth warms. Triggers include both pollen (particularly ryegrass pollen) and fungal spores. Individual risk factors include outdoor exposure, sensitivity to triggering allergens and history of seasonal allergic rhinitis. History of asthma is not a strong risk factor but is associated with severity of outcome. Limited data on demographic characteristics suggests that individuals aged between 20 and 60 and (in Australasia) of Asian/Indian ethnicity are at higher risk. A single TA event has been reported in New Zealand to date, but much of New Zealand may be at risk of future events given that ryegrass pastures are widely distributed, and summer thunderstorms can occur anywhere. CONCLUSIONS: We recommend developing rapidly deployable public messaging to support the health emergency management response to future TA events, together with the instigation of routine aeroallergen monitoring.

A Genome-wide Association Study of Circulating Levels of Atorvastatin and Its Major Metabolites.

Atorvastatin (ATV) is frequently prescribed and generally well  tolerated, but can lead to myotoxicity, especially at higher doses. A genome-wide association study of circulating levels of ATV, 2-hydroxy (2-OH) ATV, ATV lactone (ATV L), and 2-OH ATV L was performed in 590 patients who had been hospitalized with a non-ST elevation acute coronary syndrome 1 month earlier and were on high-dose ATV (80 mg or 40 mg daily). The UGT1A locus (lead single nucleotide polymorphism, rs887829) was strongly associated with both increased 2-OH ATV/ATV (P = 7.25 × 10-16 ) and 2-OH ATV L/ATV L (P = 3.95 × 10-15 ) metabolic ratios. Moreover, rs45446698, which tags CYP3A7*1C, was nominally associated with increased 2-OH ATV/ATV (P = 6.18 × 10-7 ), and SLCO1B1 rs4149056 with increased ATV (P = 2.21 × 10-6 ) and 2-OH ATV (P = 1.09 × 10-6 ) levels. In a subset of these patients whose levels of ATV and metabolites had also been measured at 12 months after hospitalization (n = 149), all of these associations remained, except for 2-OH ATV and rs4149056 (P = 0.057). Clinically, rs4149056 was associated with increased muscular symptoms (odds ratio (OR) 3.97; 95% confidence interval (CI) 1.29-12.27; P = 0.016) and ATV intolerance (OR 1.55; 95% CI 1.09-2.19; P = 0.014) in patients (n = 870) primarily discharged on high-dose ATV. In summary, both novel and recognized genetic associations have been identified with circulating levels of ATV and its major metabolites. Further study is warranted to determine the clinical utility of genotyping rs4149056 in patients on high-dose ATV.

Acute lacerations: Assessment and non-surgical management.

BACKGROUND: Given appropriate case selection and capability, many acute lacerations can be managed in the primary care setting. An understanding of the basic pathophysiology, assessment and management principles is essential. OBJECTIVE: The aim of this article is to provide a basic framework for assessing and managing simple acute lacerations. DISCUSSION: The aim of assessment is initially to decide whether the laceration is suitable for office-based treatment, and then whether it requires formal surgical closure with sutures or staples. Two non-surgical techniques for skin closure in amenable wounds are described. A companion article in this issue provides details of surgical closure techniques and wound aftercare.

STRFs in primary auditory cortex emerge from masking-based statistics of natural sounds.

We investigate how the neural processing in auditory cortex is shaped by the statistics of natural sounds. Hypothesising that auditory cortex (A1) represents the structural primitives out of which sounds are composed, we employ a statistical model to extract such components. The input to the model are cochleagrams which approximate the non-linear transformations a sound undergoes from the outer ear, through the cochlea to the auditory nerve. Cochleagram components do not superimpose linearly, but rather according to a rule which can be approximated using the max function. This is a consequence of the compression inherent in the cochleagram and the sparsity of natural sounds. Furthermore, cochleagrams do not have negative values. Cochleagrams are therefore not matched well by the assumptions of standard linear approaches such as sparse coding or ICA. We therefore consider a new encoding approach for natural sounds, which combines a model of early auditory processing with maximal causes analysis (MCA), a sparse coding model which captures both the non-linear combination rule and non-negativity of the data. An efficient truncated EM algorithm is used to fit the MCA model to cochleagram data. We characterize the generative fields (GFs) inferred by MCA with respect to in vivo neural responses in A1 by applying reverse correlation to estimate spectro-temporal receptive fields (STRFs) implied by the learned GFs. Despite the GFs being non-negative, the STRF estimates are found to contain both positive and negative subfields, where the negative subfields can be attributed to explaining away effects as captured by the applied inference method. A direct comparison with ferret A1 shows many similar forms, and the spectral and temporal modulation tuning of both ferret and model STRFs show similar ranges over the population. In summary, our model represents an alternative to linear approaches for biological auditory encoding while it captures salient data properties and links inhibitory subfields to explaining away effects.

Development and validation of a spectro-temporal processing test for cochlear-implant listeners.

Psychophysical tests of spectro-temporal resolution may aid the evaluation of methods for improving hearing by cochlear implant (CI) listeners. Here the STRIPES (Spectro-Temporal Ripple for Investigating Processor EffectivenesS) test is described and validated. Like speech, the test requires both spectral and temporal processing to perform well. Listeners discriminate between complexes of sine sweeps which increase or decrease in frequency; difficulty is controlled by changing the stimulus spectro-temporal density. Care was taken to minimize extraneous cues, forcing listeners to perform the task only on the direction of the sweeps. Vocoder simulations with normal hearing listeners showed that the STRIPES test was sensitive to the number of channels and temporal information fidelity. An evaluation with CI listeners compared a standard processing strategy with one having very wide filters, thereby spectrally blurring the stimulus. Psychometric functions were monotonic for both strategies and five of six participants performed better with the standard strategy. An adaptive procedure revealed significant differences, all in favour of the standard strategy, at the individual listener level for six of eight CI listeners. Subsequent measures validated a faster version of the test, and showed that STRIPES could be performed by recently implanted listeners having no experience of psychophysical testing.

Perception of stochastic envelopes by normal-hearing and cochlear-implant listeners.

We assessed auditory sensitivity to three classes of temporal-envelope statistics (modulation depth, modulation rate, and comodulation) that are important for the perception of 'sound textures'. The textures were generated by a probabilistic model that prescribes the temporal statistics of a selected number of modulation envelopes, superimposed onto noise carriers. Discrimination thresholds were measured for normal-hearing (NH) listeners and users of a MED-EL pulsar cochlear implant (CI), for separate manipulations of the average rate and modulation depth of the envelope in each frequency band of the stimulus, and of the co-modulation between bands. Normal-hearing (NH) listeners' discrimination of envelope rate was similar for baseline modulation rates of 5 and 34 Hz, and much poorer than previously reported for sinusoidally amplitude-modulated sounds. In contrast, discrimination of model parameters that controlled modulation depth was poorer at the lower baseline rate, consistent with the idea that, at the lower rate, subjects get fewer 'looks' at the relevant information when comparing stimuli differing in modulation depth. NH listeners could discriminate differences in co-modulation across bands; a multidimensional scaling study revealed that this was likely due to genuine across-frequency processing, rather than within-channel cues. CI users' discrimination performance was worse overall than for NH listeners, but showed a similar dependence on stimulus parameters.

A role for amplitude modulation phase relationships in speech rhythm perception.

Prosodic rhythm in speech [the alternation of "Strong" (S) and "weak" (w) syllables] is cued, among others, by slow rates of amplitude modulation (AM) within the speech envelope. However, it is unclear exactly which envelope modulation rates and statistics are the most important for the rhythm percept. Here, the hypothesis that the phase relationship between "Stress" rate (∼2 Hz) and "Syllable" rate (∼4 Hz) AMs provides a perceptual cue for speech rhythm is tested. In a rhythm judgment task, adult listeners identified AM tone-vocoded nursery rhyme sentences that carried either trochaic (S-w) or iambic patterning (w-S). Manipulation of listeners' rhythm perception was attempted by parametrically phase-shifting the Stress AM and Syllable AM in the vocoder. It was expected that a 1π radian phase-shift (half a cycle) would reverse the perceived rhythm pattern (i.e., trochaic → iambic) whereas a 2π radian shift (full cycle) would retain the perceived rhythm pattern (i.e., trochaic → trochaic). The results confirmed these predictions. Listeners judgments of rhythm systematically followed Stress-Syllable AM phase-shifts, but were unaffected by phase-shifts between the Syllable AM and the Sub-beat AM (∼14 Hz) in a control condition. It is concluded that the Stress-Syllable AM phase relationship is an envelope-based modulation statistic that supports speech rhythm perception.

Intake patterns of food nutrients and other substances associated with chronic pancreatitis.

BACKGROUND/OBJECTIVES: While alcohol is considered the most common aetiological factor for chronic pancreatitis, the intake of various nutrient and other substances is thought to act as cofactors in the pathogenesis of the disease due to modulation of oxidative stress. This study examined incident cases of acute pancreatitis to determine the dietary and other intakes that characterize those harbouring underlying chronic pancreatitis. METHODS: Cases of acute pancreatitis presenting to a single institution were prospectively recruited (n = 153). The presence of chronic pancreatitis was defined by a composite of clinical, biochemical and radiological criteria. Information was obtained on the intake of dietary macro- and micronutrients, coffee, tobacco and alcohol in the period just prior to the acute exacerbation. Univariate and multivariate analyses of association were undertaken. Principal components analysis (PCA) was employed to elicit patterns of intake. RESULTS: After adjustment for key demographic variables, no individual nutrient or other substance showed a significant association with chronic pancreatitis. However, following PCA there emerged a significant positive association with a so-called "stimulant" intake pattern and a negative association with a so-called "nutritive" pattern. CONCLUSIONS: Preceding an acute exacerbation, patients with underlying chronic pancreatitis are more likely to substitute food-based intake for combinations of other substances, such as tobacco and coffee. This finding may have application in the clinical setting as part of a chronic disease management protocol.

Inhibition of immune activation by a novel nuclear factor-kappa B inhibitor in HTLV-I-associated neurologic disease.

The human T-lymphotropic virus type I (HTLV-I) causes a chronic inflammatory disorder of the central nervous system termed HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-I encodes a protein known to activate several host-signaling pathways involved in inflammation, such as the nuclear factor-κB (NF-κB). The contribution of the NF-κB pathway to the pathogenesis of HAM/TSP, however, has not been fully defined. We show evidence of canonical NF-κB activation in short-term cultures of peripheral blood mononuclear cells (PBMCs) from subjects with HAM/TSP. NF-κB activation was closely linked to HTLV-I viral protein expression. The NF-κB activation in HAM/TSP PBMCs was reversed by a novel small-molecule inhibitor that demonstrates potent and selective NF-κB antagonist activity. Inhibition of NF-κB activation led to a reduction in the expression of lymphocyte activation markers and resulted in reduced cytokine signaling in HAM/TSP PBMCs. Furthermore, NF-κB inhibition led to a reduction in spontaneous lymphoproliferation, a key ex vivo correlate of the immune activation associated with HAM/TSP. These results indicate that NF-κB activation plays a critical upstream role in the immune activation of HAM/TSP, and identify the NF-κB pathway as a potential target for immunomodulation in HAM/TSP.

Enzyme potentiated desensitisation in treatment of seasonal allergic rhinitis: double blind randomised controlled study.

OBJECTIVE: To assess the efficacy of enzyme potentiated desensitisation in the treatment of severe summer hay fever poorly controlled by pharmacotherapy. DESIGN: Double blind randomised placebo controlled parallel group study. SETTING: Hospital in Hampshire. PARTICIPANTS: 183 participants aged between 18 and 64 with a history of severe summer hay fever for at least two years; all were skin prick test positive to timothy grass pollen. 90 randomised to active treatment; 93 randomised to placebo. INTERVENTIONS: Active treatment: two injections of enzyme potentiated desensitisation, given between eight and 11 weeks apart, each comprising 200 Fishman units of beta glucuronidase, 50 pg 1,3-cyclohexanediol, 50 ng protamine sulphate, and a mixed inhaled allergen extract (pollen mixes for trees, grasses, and weeds; allergenic fungal spores; cat and dog danders; dust and storage mites) in a total volume of 0.05 ml of buffered saline. Placebo: two injections of 0.05 ml buffered saline solution. MAIN OUTCOME MEASURES: Proportion of problem-free days; global rhinoconjunctivitis quality of life scores assessed weekly during pollen season. RESULTS: The active treatment group and the placebo group did not differ in the proportion of problem-free days, quality of life scores, symptom severity scores, change in quantitative skin prick provocation threshold, or change in conjunctival provocation threshold. No clinically significant adverse reactions occurred. CONCLUSIONS: Enzyme potentiated desensitisation showed no treatment effect in this study.