Tunable beam shaping with a phased array acousto-optic modulator.

We demonstrate the generation of Bessel beams using an acousto-optic array based on a liquid filled cavity surrounded by a cylindrical multi-element ultrasound transducer array. Conversion of a Gaussian laser mode into a Bessel beam with tunable order and position is shown. Also higher-order Bessel beams up to the fourth order are successfully generated with experimental results very closely matching simulations.

A randomised, single-blind technical study comparing the ultrasonic visibility of smooth-surfaced and textured needles in a soft embalmed cadaver model.

Visibility of the needle tip and shaft is important during ultrasound-guided regional anaesthesia in order to prevent nerve trauma. Tip and shaft visibility is reduced when needles are inserted in-plane at wide angles and out-of-plane at narrow angles to the ultrasound probe. Although textured needles are more reflective than smooth needles, we hypothesised that poor visibility of the tip and shaft still remained using the above angle-probe combinations. In a single-blind study, we compared the visibility of a textured Tuohy needle, a textured single-shot needle and a conventional smooth-surfaced Tuohy needle when inserted into the biceps and deltoid muscles of a soft embalmed cadaver. One hundred and forty-four needles were block-randomised to in-plane and out-of-plane insertions at 30°, 45°, 60° and 75° to the ultrasound beam. Two blinded raters assessed needle tip visibility on video recordings of the insertions using a binary scale (0 = not visible, 1 = visible) and shaft visibility using a 5-point Likert scale. The median (IQR [range]) proportions of visible needle tips were 83% (67-83 [50-100]%) for the textured Tuohy, 75% (67-83 [33-83]%) for the textured single-shot needle and 33% (33-46 [0-50]%) for the smooth-surfaced Tuohy (p = 0.0007). Median (IQR [range]) needle shaft visibility was rated as 4.0 (3.5-4.7 [3.0-4.9]) for the textured Tuohy, 4.0 (3.8-4.5 [2.7-4.9]) for the textured single-shot needle and 3.0 (2.4-3.3 [2.3-3.5]) for the smooth-surfaced Tuohy (p = 0.015). Nevertheless, visibility was reduced at wide angles in-plane and narrow angles out-of-plane both for needle tips (p = 0.004) and shafts (p = 0.005).

Magnetic skin effect in Pb(Fe _{1/2}$Nb _{1/2}$)O3.

Relaxor-ferroelectrics display exceptional dielectric properties resulting from the underlying random dipolar fields induced by strong chemical inhomogeneity. An unusual structural aspect of relaxors is a skin-effect where the near-surface region in single crystals exhibit structures and critical phenomena that differ from the bulk. Relaxors are unique in that this skin effect extends over a macroscopic lengthscale of ∼100 µmwhereas usual surface layers only extend over a few unit cells (or ∼nm). We present a muon spectroscopy study of Pb(Fe_{1/2}Nb_{1/2})O3(PFN) which displays ferroelectric order, including many relaxor-like dielectric properties such as a frequency broadened dielectric response, and antiferromagnetism with spatially short-range polar correlations and hence can be termed a multiferroic. In terms of the magnetic behavior determined by the Fe3+(S=5/2,L ≈ 0) ions, PFN has been characterized as a unique example of a 'cluster spin-glass'. We use variable momentum muon spectroscopy to study the depth dependence of the slow magnetic relaxations in a large 1 cm3crystal of PFN. Zero-fieldpositivemuon spin relaxation is parameterized using a stretched exponential, indicative of a distribution of relaxation rates of the Fe3+spins. This bandwidth of frequencies changes as a function of muon momentum, indicative of a change in the Fe3+relaxation rates as a function of muon implantation depth in our single crystal. Usingnegativemuon elemental analysis, we find small-to-no measurable change in the Fe3+/Nb5+concentration with depth implying that chemical concentration alone cannot account for the change in the relaxational dynamics. PFN displays an analogous magnetic skin effect reported to exist in the structural properties of relaxor-ferroelectrics.

Translation of sonoelastography from Thiel cadaver to patients for peripheral nerve blocks.

Ultrasound guidance is now common in regional anaesthesia practice, but remains limited by poor visibility of the needle tip and poor quantification of local anaesthetic spread. Sonoelastography based on tissue compression is a technique depicting tissue strain. Hitherto used largely for tumour diagnosis, we used it in both Thiel embalmed cadavers and two patients receiving interscalene and femoral blocks to observe changes in tissue strain during local anaesthetic injection. The primary aim of our study was to measure the area under the curve (weighted for time) of the strain pattern in Thiel perineural tissue when using a range of volumes of embalming fluid (0.25, 0.5, 1, 2.5, 5 and 7.5 ml) for interscalene and femoral blocks using sonoelastography. Our secondary aims were to evaluate static images of anatomy and videos of needle insertion and perineural injection using combined B-Mode ultrasound and sonoelastography. Independent raters assessed the anatomy and spread using a 7-point Likert scale, ranked from extremely poor to extremely good. We performed 83 blocks in cadavers. Concordance between both raters was good, with weighted Kappa (95% CI) 0.66 (0.61-0.71). The characteristics of spread were similar with both interscalene and femoral block; spread increased with injectate volume up to 1 ml. Analysis of variance showed differences in spread between injection volumes (p = 0.009), but not between regional blocks (p = 0.05). Post-hoc analysis showed greater spread with 1 and 2.5 ml volumes compared with 0.25 ml. In patients, visibility of strain during injection was better with sonoelastography than with B-Mode ultrasound and showed a dose response from 1 to 5 ml volumes of local anaesthetic. Colour strain recognition using sonoelastography offers the ability to differentiate between nerve and surrounding tissue during local anaesthetic injection by improving visibility of spread (p = 0.04).

Etomidate unmasks intraadrenal regulation of steroidogenesis and proliferation in adrenal cortical cell lines.

To characterize intraadrenal adaptations for inhibition of cortisol synthesis, we analyzed the effects of etomidate (ETO) on steroid hormone secretion and expression of key regulators of steroidogenesis and proliferation in human NCI-h295 adrenocortical cancer cells. Etomidate potently blocked 11beta-hydroxylase (CYP11B1), aldosterone synthase (CYP11B2), and side chain cleavage enzyme (CYP11A1). This inhibition of steroidogenesis was associated with increased expression of steroidogenic acute regulatory protein (StAR), and CYP11A1 and 17alpha-hydroxylase/17, 20-lyase (CYP17A1) protein levels, but not of the respective mRNA levels. Promoter activity of CYP11A1 and melanocortin 2 receptor (MC2R) was not increased by etomidate in treated cells compared to controls. The increase in protein levels was partially reversed by cycloheximide suggesting post-transcriptional mechanisms but also protein stabilization as underlying cause. Furthermore, ETO exhibited antiproliferative activity paralleled by a decrease in phosphorylation of MEK and ERK1, 2. In summary, ETO exhibits pleiotropic effects on adrenal function in vitro. Inhibition of steroidogenesis is followed by increased levels of steroidogenic key proteins and reduced proliferation. These changes reflect adaptations to maintain steroidogenesis at the cost of adrenal proliferation.

Manipulation of microparticles using phase-controllable ultrasonic standing waves.

A method of manipulating microparticles in a liquid using ultrasound is proposed and demonstrated. An ultrasonic standing wave with nodal planes whose positions are controllable by varying the relative phase of two applied sinusoidal signals is generated using a pair of acoustically matched piezoelectric transducers. The resulting acoustic radiation force is used to trap micron scale particles at a series of arbitrary positions (determined by the relative phase) and then move them in a controlled manner. This method is demonstrated experimentally and 5 µm polystyrene particles are trapped and moved in one dimension through 140 µm.

Albuterol metered dose inhaler performance under hyperbaric pressures.

The weight change per actuation and aerosol particle size and number delivered by albuterol metered dose inhalers (MDIs) were measured in a multiplace hyperbaric chamber at pressures ranging from one atmosphere absolute (1 ATA, 0 feet of seawater, fsw, 101 kPa) to three ATA (66 fsw, 304 kPa). Weight change per actuation by CFC (chlorofluorocarbon) and long canister HFA (hydrofluoroalkane) powered MDIs was 13 +/- 1% and 12 +/- 1% less, respectively, at 3 ATA compared to 1 ATA. However, weight change per actuation by short canister HFA MDIs was not significantly changed with pressure. The geometric mean diameters of nano particles from the CFC and short canister HFA MDIs decreased from 50 nm at 0 fsw to 32 nm at 66 fsw whereas the long canister HFA aerosol diameters were not affected. The numbers of nanometer size particles delivered at 66 fsw were only 4-7% of those delivered at 0 fsw for the CFC and long canister HFA MDIs whereas for the short canister MDIs it was 26%. We conclude that the weight change per actuation of albuterol and the sizes and numbers of aerosol particles emitted from albuterol MDIs actuated in a hyperbaric environment vary by canister type.

Common acoustic phonon lifetimes in inorganic and hybrid lead halide perovskites.

The acoustic phonons in the organic-inorganic lead halide perovskites have been reported to have anomalously short lifetimes over a large part of the Brillouin zone. The resulting shortened mean free paths of the phonons have been implicated as the origin of the low thermal conductivity. We apply neutron spectroscopy to show that the same acoustic phonon energy linewidth broadening (corresponding to shortened lifetimes) occurs in the fully inorganic CsPbBr3 by comparing the results on the organic-inorganic CH3NH3PbCl3. We investigate the critical dynamics near the three zone boundaries of the cubic P m 3 ¯ m Brillouin zone of CsPbBr3 and find energy and momentum broadened dynamics at momentum points where the Cs-site (A-site) motions contribute to the cross section. Neutron diffraction is used to confirm that both the Cs and Br sites have unusually large thermal displacements with an anisotropy that mirrors the low temperature structural distortions. The presence of an organic molecule is not necessary to disrupt the low-energy acoustic phonons at momentum transfers located away from the zone center in the lead halide perovskites and such damping may be driven by the large displacements or possibly disorder on the A site.

Modelling prefrontal cortex deficits in schizophrenia: implications for treatment.

Current treatments of schizophrenia are compromised by their inability to treat all symptoms of the disease and their side-effects. Whilst existing antipsychotic drugs are effective against positive symptoms, they have negligible efficacy against the prefrontal cortex (PFC)-associated cognitive deficits and negative symptoms. New models that reproduce core pathophysiological features of schizophrenia are more likely to have improved predictive validity in identifying new treatments. We have developed a NMDA receptor antagonist model that reproduces core PFC deficits of schizophrenia and discuss this in relation to pathophysiology and treatments. Subchronic and chronic intermittent PCP (2.6 mg/kg i.p.) was administered to rats. PFC activity was assessed by 2-deoxyglucose imaging, parvalbumin and Kv3.1 mRNA expression, and the attentional set-shifting test (ASST) of executive function. Affymetrix gene array technology was employed to examine gene expression profile patterns. PCP treatment reduced glucose utilization in the PFC (hypofrontality). This was accompanied by a reduction in markers of GABAergic interneurones (parvalbumin and Kv3.1 mRNA expression) and deficits in the extradimensional shift dimension of the ASST. Consistent with their clinical profile, the hypofrontality was not reversed by clozapine or haloperidol. Transcriptional analysis revealed patterns of change consistent with current neurobiological theories of schizophrenia. This model mirrors core neurobiological deficits of schizophrenia; hypofrontality, altered markers of GABAergic interneurone activity and deficits in executive function. As such it is likely to be a valuable translational model for understanding the neurobiological mechanisms underlying hypofrontality and for identifying and validating novel drug targets that may restore PFC deficits in schizophrenia.

Agreement Among 4 Sampling Methods to Identify Respiratory Pathogens in Dairy Calves with Acute Bovine Respiratory Disease.

BACKGROUND: Four sampling techniques commonly are used for antemortem identification of pathogens from cattle with bovine respiratory disease (BRD): the nasal swab (NS), guarded nasopharyngeal swab (NPS), bronchoalveolar lavage (BAL), and transtracheal wash (TTW). Agreement among these methods has not been well characterized. OBJECTIVE: To evaluate agreement among TTW and NS, NPS, or BAL for identification of viral and bacterial pathogens in dairy calves with BRD. ANIMALS: One hundred dairy calves with naturally acquired BRD. METHODS: Calves were sampled by all 4 methods. Viral agents were identified by real-time RT-PCR, bacteria were identified by aerobic culture, and Mycoplasma bovis (M. bovis) isolates were speciated by PCR. Agreement among TTW and NS, NPS, or BAL was evaluated by calculating the kappa statistic and percent positive agreement. McNemar's exact test was used to compare the proportions of positive results. RESULTS: Agreement among TTW and NS, TTW and NPS, and TTW and BAL, was very good for identification of P. multocida, M. haemolytica, and M. bovis. For bovine respiratory syncytial virus (BRSV), agreement with TTW was moderate for NS, good for NPS, and very good for BAL. For bovine coronavirus (BCV), agreement with TTW was moderate for NS and NPS, and good for BAL. McNemar's test was significant only for BCV, indicating that for this pathogen the proportion of positive results from NS and NPS could not be considered comparable to TTW. CONCLUSIONS AND CLINICAL IMPORTANCE: This study provides guidance for veterinarians selecting diagnostic tests for antemortem identification of pathogens associated with BRD.

Modelling and characterisation of a ultrasound-actuated needle for improved visibility in ultrasound-guided regional anaesthesia and tissue biopsy.

Clear needle visualisation is recognised as an unmet need for ultrasound guided percutaneous needle procedures including regional anaesthesia and tissue biopsy. With inadequate needle visibility, these procedures may result in serious complications or a failed operation. This paper reports analysis of the modal behaviour of a previously proposed ultrasound-actuated needle configuration, which may overcome this problem by improving needle visibility in colour Doppler imaging. It uses a piezoelectric transducer to actuate longitudinal resonant modes in needles (outer diameter 0.8-1.2mm, length>65mm). The factors that affect the needle's vibration mode are identified, including the needle length, the transducer's resonance frequency and the gripping position. Their effects are investigated using finite element modelling, with the conclusions validated experimentally. The actuated needle was inserted into porcine tissue up to 30mm depth and its visibility was observed under colour Doppler imaging. The piezoelectric transducer is able to generate longitudinal vibration with peak-to-peak amplitude up to 4µm at the needle tip with an actuating voltage of 20Vpp. Actuated in longitudinal vibration modes (distal mode at 27.6kHz and transducer mode at 42.2kHz) with a drive amplitude of 12-14Vpp, a 120mm needle is delineated as a coloured line in colour Doppler images, with both needle tip and shaft visualised. The improved needle visibility is maintained while the needle is advanced into the tissue, thus allowing tracking of the needle position in real time. Moreover, the needle tip is highlighted by strong coloured artefacts around the actuated needle generated by its flexural vibration. A limitation of the technique is that the transducer mode requires needles of specific lengths so that the needle's resonance frequency matches the transducer. This may restrict the choice of needle lengths in clinical applications.

Increased variability in Apc(Min)/+ intestinal tissue can be measured with microultrasound.

Altered tissue structure is a feature of many disease states and is usually measured by microscopic methods, limiting analysis to small areas. Means to rapidly and quantitatively measure the structure and organisation of large tissue areas would represent a major advance not just for research but also in the clinic. Here, changes in tissue organisation that result from heterozygosity in Apc, a precancerous situation, are comprehensively measured using microultrasound and three-dimensional high-resolution microscopy. Despite its normal appearance in conventionally examined cross-sections, both approaches revealed a significant increase in the variability of tissue organisation in Apc heterozygous tissue. These changes preceded the formation of aberrant crypt foci or adenoma. Measuring these premalignant changes using microultrasound provides a potential means to detect microscopically abnormal regions in large tissue samples, independent of visual examination or biopsies. Not only does this provide a powerful tool for studying tissue structure in experimental settings, the ability to detect and monitor tissue changes by microultrasound could be developed into a powerful adjunct to screening endoscopy in the clinic.

The novel long PDE4A10 cyclic AMP phosphodiesterase shows a pattern of expression within brain that is distinct from the long PDE4A5 and short PDE4A1 isoforms.

In situ hybridisation methods were used to map the distribution of the novel long PDE4A10 isoform in the brain. PDE4A10 distribution was compared to that of the long PDE4A5 isoform and the short PDE4A1 isoform using probes specific for unique sequences within each of these isoforms. Coronal sections of the brain, taken at the level of the olfactory bulb, prefrontal cortex, striatum, thalamus, hippocampus and cerebellum, were analysed. Strongest expression of PDE4A isoforms was found in the olfactory bulb granular layer with high signals also in the piriform cortex, the dentate gyrus and the CA1 and CA2 pyramidal cells. For the two long forms, level general staining was noted throughout the striatum, thalamus and hippocampus but no signal was evident in the cerebellum. The long PDE4A10 and PDE4A5 isoforms localised to essentially the same regions throughout the brain, although PDE4A10 was uniquely expressed in the major island of Calleja. A signal for the short PDE4A1 isoform was found in regions in which the two long isoforms were both expressed, with the exception of the medial nucleus of the amygdala where weak signals for PDE4A5 and PDE4A10 were detected but PDE4A1 was absent. Uniquely, strong signals for PDE4A1 were detected in the glomerular layer of the olfactory bulb, the CA3 pyramidal cell region and the cerebellum; areas where signals for the two long forms were not evident. PDE4A transcripts for both PDE4A5 and PDE4A10 were not apparent in the brain stem and those for PDE4A1 were low. PDE4A isoforms are present in several key areas of the brain and therefore present valid targets for therapeutic interventions. Whilst the two long PDE4A isoforms show a remarkably similar distribution, in at least three regions there is clear segregation between their pattern of expression and that of the PDE4A1 short form. This identifies differential regulation of the expression of PDE4A long and short isoforms. We suggest that specific PDE4A isoforms may have distinct functional roles in the brain, indicating that PDE4A isoform-selective inhibitors may have specific therapeutic and pharmacologic properties.

Isolation of Mycoplasma pneumoniae from synovial fluid samples in a patient with pneumonia and polyarthritis.

A patient with a long history of arthritis developed pneumonia. Two weeks into her hospital course, the patient developed effusions in her knee and wrist that yielded cultures positive for Mycoplasma pneumoniae. To our knowledge, this is the third reported case of M pneumoniae isolation from a joint and the first report of isolation of M pneumoniae from two joints in a patient without hypogammaglobulinemia. The evidence suggests that in individuals with atypical pneumonia and joint effusions, M pneumoniae should be considered as a source of infection.

Alignment of an acoustic manipulation device with cepstral analysis of electronic impedance data.

Acoustic particle manipulation is an emerging technology that uses ultrasonic standing waves to position objects with pressure gradients and acoustic radiation forces. To produce strong standing waves, the transducer and the reflector must be aligned properly such that they are parallel to each other. This can be a difficult process due to the need to visualise the ultrasound waves and as higher frequencies are introduced, this alignment requires higher accuracy. In this paper, we present a method for aligning acoustic resonators with cepstral analysis. This is a simple signal processing technique that requires only the electrical impedance measurement data of the resonator, which is usually recorded during the fabrication process of the device. We first introduce the mathematical basis of cepstral analysis and then demonstrate and validate it using a computer simulation of an acoustic resonator. Finally, the technique is demonstrated experimentally to create many parallel linear traps for 10 µm fluorescent beads inside an acoustic resonator.

Use of protein A immunoadsorption as a treatment for thrombocytopenia in HIV-infected homosexual men: a retrospective evaluation of 37 cases.

Thirty-seven HIV-infected homosexual men with thrombocytopenia (less than 100 x 10(9)/l) received protein A immunoadsorption treatments to remove platelet-sensitizing immunoglobulin (Ig) G and circulating immune complexes (CIC) from plasma. Patients received an average of six treatments each, consisting of 250 ml plasma over a 3-week period. Clinical improvement in hemorrhagic symptoms associated with substantial increase in platelet counts was achieved in 18 patients. These responses were maintained over a median follow-up period of more than 7 months in 14 evaluable patients who were not lost to follow-up (three patients relapsed in 2 weeks and one received another therapy). Generally, moderate transient treatment-related side-effects included fever, musculoskeletal pain, chills and nausea. A transient serum sickness-like reaction was observed in seven patients, leading to termination of treatment in two. Clinical responses were associated with significant decreases in levels of platelet-sensitizing Ig, including CIC. Stimulation of broadly cross-reactive anti-antigen-binding fragment [F(ab)2], antibodies contributed to these responses. Protein A immunoadsorption is an effective alternative treatment for HIV-associated thrombocytopenia.

Depressive distress among homosexually active African American men and women.

OBJECTIVE: Although early surveys of psychological adjustment among gay men and lesbians suggest only minor and not clinically relevant differences from heterosexual populations, concerns about psychiatric morbidity associated with HIV infection have renewed interest in the prevalence of psychological distress in this population, particularly among gay men. These later studies have focused primarily on white men. However, research indicates higher crude prevalence rates of psychological distress in community-drawn samples of African American subjects than in white subjects and also higher rates in women than in men. The authors examined rates of depressive distress and suicidal thoughts among homosexually active African American men and women who might be especially at risk for psychiatric morbidity due to multiple stigmatized social statuses. METHOD: Two nationally recruited groups of homosexually active African Americans (829 men and 603 women) completed self-administered questionnaires, including the Center for Epidemiologic Studies Depression Scale. RESULTS: Homosexually active black women were as distressed as HIV-infected gay black men. Men with symptomatic HIV disease were significantly more distressed than men who were HIV infected but asymptomatic, HIV-antibody negative, or whose HIV status was unknown. Both men and women reported distress levels in excess of those previously reported in studies of blacks or primarily white gay men. CONCLUSIONS: Further research is needed to identify specific predictors of life stressors and lack of social support among homosexually active African Americans who appear to be at higher risk for depressive distress.

Cloning and sequencing of a human thioredoxin reductase.

The DNA sequence encoding human placental thioredoxin reductase has been determined. Of the 3826 base pairs sequenced, 1650 base pairs were in an open reading frame encoding a mature protein with 495 amino acids and a calculated molecular mass of 54,171. Sequence analysis showed strong similarity to glutathione reductases and other NADPH-dependent reductases. Human thioredoxin reductase contains the redox-active cysteines in the putative FAD binding domain and has a dimer interface domain not previously seen with prokaryote and lower eukaryote thioredoxin reductases.

Patterns of cell death in mouse anteroventral cochlear nucleus neurons after unilateral cochlea removal.

Developmental changes that influence the results of removal of afferent input on the survival of neurons of the anteroventral cochlear nucleus (AVCN) of mice were examined with the hope of providing a suitable model for understanding the cellular and molecular basis for these developmental changes in susceptibility. We performed unilateral cochlear ablation on wild-type mice at a variety of ages around the time of hearing onset to determine developmental changes in the sensitivity of AVCN neurons to afferent deprivation. In postnatal day 5 (P5) mice, cochlea removal resulted in 61% neuronal loss in the AVCN. By age P14, fewer than 1% of AVCN neurons were lost after this manipulation. This reveals a rather abrupt change in the sensitivity to disruption of afferent input, a critical period. We next investigated the temporal events associated with neuron loss after cochlea removal in susceptible animals. We demonstrate that significant cell loss occurs within 48 hours of cochlea removal in P7 animals. Furthermore, evidence of apoptosis was observed within 12 hours of cochlea removal, suggesting that the molecular events leading to cell loss after afferent deprivation begin to occur within hours of cochlea removal. Finally, we began to examine the role of the bcl-2 gene family in regulating afferent deprivation-induced cell death in the mouse AVCN. AVCN neurons in mature bcl-2 knockout mice demonstrate susceptibility to removal of afferent input comparable to neonatal sensitivity of wild-type controls. These data suggest that bcl-2 is one effector of cell survival as these cells switch from afferent-dependent to -independent survival mechanisms.

Developmental regulation of EphA4 expression in the chick auditory brainstem.

The avian auditory brainstem nuclei nucleus magnocellularis (NM) and nucleus laminaris (NL) display highly precise patterns of neuronal connectivity. NM projects tonotopically to the dorsal dendrites of ipsilateral NL neurons and to the ventral dendrites of contralateral NL neurons. The precision of this binaural segregation is evident at the earliest developmental stage at which connections can be observed. We have begun to examine the possibility that Eph receptor tyrosine kinase signaling is involved in establishing these spatially segregated connections. The expression of the EphA4 tyrosine kinase was examined at several developmental stages. EphA4 is expressed in rhombomere 5, which contains progenitors for both NM and NL. In this rhombomere, the labeling becomes striped during the time that precursor cells migrate to the auditory anlage. At the precise time when NM-NL projections are forming, EphA4 expression in NL is asymmetric, with markedly higher expression in the dorsal NL neuropil than in the ventral neuropil, suggesting a possible role in guiding growing axons to the appropriate region. At later embryonic ages EphA4 expression is symmetric around NL, and is absent in NM. As auditory function matures, EphA4 expression decreases so that by 4 days after hatch no EphA4 antibody labeling is evident in the auditory brainstem nuclei.