CLEAR - clozapine in early psychosis: study protocol for a multi-centre, randomised controlled trial of clozapine vs other antipsychotics for young people with treatment resistant schizophrenia in real world settings.

BACKGROUND: Clozapine is an antipsychotic drug with unique efficacy, and it is the only recommended treatment for treatment-resistant schizophrenia (TRS: failure to respond to at least two different antipsychotics). However, clozapine is also associated with a range of adverse effects which restrict its use, including blood dyscrasias, for which haematological monitoring is required. As treatment resistance is recognised earlier in the illness, the question of whether clozapine should be prescribed in children and young people is increasingly important. However, most research to date has been in older, chronic patients, and evidence regarding the efficacy and safety of clozapine in people under age 25 is lacking. The CLEAR (CLozapine in EARly psychosis) trial will assess whether clozapine is more effective than treatment as usual (TAU), at the level of clinical symptoms, patient rated outcomes, quality of life and cost-effectiveness in people below 25 years of age. Additionally, a nested biomarker study will investigate the mechanisms of action of clozapine compared to TAU. METHODS AND DESIGN: This is the protocol of a multi-centre, open label, blind-rated, randomised controlled effectiveness trial of clozapine vs TAU (any other oral antipsychotic monotherapy licenced in the British National Formulary) for 12 weeks in 260 children and young people with TRS (12-24 years old). AIM AND OBJECTIVES: The primary outcome is the change in blind-rated Positive and Negative Syndrome Scale scores at 12 weeks from baseline. Secondary outcomes include blind-rated Clinical Global Impression, patient-rated outcomes, quality of life, adverse effects, and treatment adherence. Patients will be followed up for 12 months and will be invited to give consent for longer term follow-up using clinical records and potential re-contact for further research. For mechanism of action, change in brain magnetic resonance imaging (MRI) biomarkers and peripheral inflammatory markers will be measured over 12 weeks. DISCUSSION: The CLEAR trial will contribute knowledge on clozapine effectiveness, safety and cost-effectiveness compared to standard antipsychotics in young people with TRS, and the results may guide future clinical treatment recommendation for early psychosis. TRIAL REGISTRATION: ISRCTN Number: 37176025, IRAS Number: 1004947. TRIAL STATUS: In set-up. Protocol version 4.0 01/08/23. Current up to date protocol available here: https://fundingawards.nihr.ac.uk/award/NIHR131175# /.

Defining α-synuclein species responsible for Parkinson's disease phenotypes in mice.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by fibrillar neuronal inclusions composed of aggregated α-synuclein (α-syn). These inclusions are associated with behavioral and pathological PD phenotypes. One strategy for therapeutic interventions is to prevent the formation of these inclusions to halt disease progression. α-Synuclein exists in multiple structural forms, including disordered, nonamyloid oligomers, ordered amyloid oligomers, and fibrils. It is critical to understand which conformers contribute to specific PD phenotypes. Here, we utilized a mouse model to explore the pathological effects of stable ß-amyloid-sheet oligomers compared with those of fibrillar α-synuclein. We biophysically characterized these species with transmission EM, atomic-force microscopy, CD spectroscopy, FTIR spectroscopy, analytical ultracentrifugation, and thioflavin T assays. We then injected these different α-synuclein forms into the mouse striatum to determine their ability to induce PD-related phenotypes. We found that ß-sheet oligomers produce a small but significant loss of dopamine neurons in the substantia nigra pars compacta (SNc). Injection of small ß-sheet fibril fragments, however, produced the most robust phenotypes, including reduction of striatal dopamine terminals, SNc loss of dopamine neurons, and motor-behavior defects. We conclude that although the ß-sheet oligomers cause some toxicity, the potent effects of the short fibrillar fragments can be attributed to their ability to recruit monomeric α-synuclein and spread in vivo and hence contribute to the development of PD-like phenotypes. These results suggest that strategies to reduce the formation and propagation of ß-sheet fibrillar species could be an important route for therapeutic intervention in PD and related disorders.

Behavioral defects associated with amygdala and cortical dysfunction in mice with seeded α-synuclein inclusions.

Parkinson's disease (PD) is defined by motor symptoms such as tremor at rest, bradykinesia, postural instability, and stiffness. In addition to the classical motor defects that define PD, up to 80% of patients experience cognitive changes and psychiatric disturbances, referred to as PD dementia (PDD). Pathologically, PD is characterized by loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and intracellular inclusions, called Lewy bodies and Lewy neurites, composed mostly of α-synuclein. Much of PD research has focused on the role of α-synuclein aggregates in degeneration of SNpc dopamine neurons because of the impact of loss of striatal dopamine on the classical motor phenotypes. However, abundant Lewy pathology is also found in other brain regions including the cortex and limbic brain regions such as the amygdala, which may contribute to non-motor phenotypes. Little is known about the consequences of α-synuclein inclusions in these brain regions, or in neuronal subtypes other than dopamine neurons. This project expands knowledge on how α-synuclein inclusions disrupt behavior, specifically non-motor symptoms of synucleinopathies. We show that bilateral injections of fibrils into the striatum results in robust bilateral α-synuclein inclusion formation in the cortex and amygdala. Inclusions in the amygdala and prefrontal cortex primarily localize to excitatory neurons, but unbiased stereology shows no significant loss of neurons in the amygdala or cortex. Fibril injected mice show defects in a social dominance behavioral task and fear conditioning, tasks that are associated with prefrontal cortex and amygdala function. Together, these observations suggest that seeded α-synuclein inclusion formation impairs behaviors associated with cortical and amygdala function, without causing cell loss, in brain areas that may play important roles in the complex cognitive features of PDD.

A core outcome set for future endometriosis research: an international consensus development study.

OBJECTIVE: To develop a core outcome set for endometriosis. DESIGN: Consensus development study. SETTING: International. POPULATION: One hundred and sixteen healthcare professionals, 31 researchers and 206 patient representatives. METHODS: Modified Delphi method and modified nominal group technique. RESULTS: The final core outcome set includes three core outcomes for trials evaluating potential treatments for pain and other symptoms associated with endometriosis: overall pain; improvement in the most troublesome symptom; and quality of life. In addition, eight core outcomes for trials evaluating potential treatments for infertility associated with endometriosis were identified: viable intrauterine pregnancy confirmed by ultrasound; pregnancy loss, including ectopic pregnancy, miscarriage, stillbirth and termination of pregnancy; live birth; time to pregnancy leading to live birth; gestational age at delivery; birthweight; neonatal mortality; and major congenital abnormalities. Two core outcomes applicable to all trials were also identified: adverse events and patient satisfaction with treatment. CONCLUSIONS: Using robust consensus science methods, healthcare professionals, researchers and women with endometriosis have developed a core outcome set to standardise outcome selection, collection and reporting across future randomised controlled trials and systematic reviews evaluating potential treatments for endometriosis. TWEETABLE ABSTRACT: @coreoutcomes for future #endometriosis research have been developed @jamesmnduffy.

Measuring Fidelity to Evidence-Based Practices: Psychometrics.

This special section presents the psychometric properties of fidelity scales used in a national mental health services project in Norway to improve the quality of care of people with psychoses. Across Norway, 39 clinical units in six health trusts participated. The project provided education, implementation support and fidelity assessments. The papers in the section address the psychometrics of fidelity measurement for the specific evidence-based practices: illness management and recovery, family psychoeducation, physical healthcare and antipsychotic medication management. Another paper analyzes the psychometrics of a scale measuring individualization and quality improvement that may be used in conjunction with fidelity scales for specific evidence-based practices. The first paper in the section presents the development and field of fidelity scales, and the two final papers with comments add some additional perspectives and discuss fidelity scales in a wider context. The psychometrics of the five scales were good to excellent. Fidelity assessment is a necessary and effective strategy for quality improvement.

The Family Psychoeducation Fidelity Scale: Psychometric Properties.

This study examined psychometric properties and feasibility of the Family Psychoeducation (FPE) Fidelity Scale. Fidelity assessors conducted reviews using the FPE fidelity scale four times over 18 months at five sites in Norway. After completing fidelity reviews, assessors rated feasibility of the fidelity review process. The FPE fidelity scale showed excellent interrater reliability (.99), interrater item agreement (88%), and internal consistency (mean = .84 across four time points). By the 18-month follow-up, all five sites increased fidelity and three reached adequate fidelity. Fidelity assessors rated feasibility as excellent. The FPE fidelity scale has good psychometric properties and is feasible for evaluating the implementation of FPE programs. Trial registration ClinicalTrials.gov Identifier: NCT03271242.

Magnetized Disruption of Inertially Confined Plasma Flows.

The creation and disruption of inertially collimated plasma flows are investigated through experiment, simulation, and analytical modeling. Supersonic plasma jets are generated by laser-irradiated plastic cones and characterized by optical interferometry measurements. Targets are magnetized with a tunable B field with strengths of up to 5 T directed along the axis of jet propagation. These experiments demonstrate a hitherto unobserved phenomenon in the laboratory, the magnetic disruption of inertially confined plasma jets. This occurs due to flux compression on axis during jet formation and can be described using a Lagrangian-cylinder model of plasma evolution implementing finite resistivity. The basic physical mechanisms driving the dynamics of these systems are described by this model and then compared with two-dimensional radiation-magnetohydrodynamic simulations. Experimental, computational, and analytical results discussed herein suggest that contemporary models underestimate the electrical conductivity necessary to drive the amount of flux compression needed to explain observations of jet disruption.

Femtosecond laser damage of germanium from near- to mid-infrared wavelengths.

Femtosecond laser-induced damage and ablation (fs-LIDA) is a rich field in extreme non-perturbative nonlinear optics with wide ranging applications, including laser micro- and nano-machining, waveguide writing, and eye surgery. Our understanding of fs-LIDA, however, is limited mostly to visible and near-infrared wavelengths. In this work, we systematically study single-shot, fs-laser ablation (fs-LIA) of single-crystal germanium from near- to mid-infrared wavelengths, and compare the fs-LIA wavelength scaling with two widely used models. We show that these models are inadequate, particularly at mid-infrared wavelengths. Instead, a hybrid model is proposed involving Keldysh ionization rates, a constant free-carrier density threshold, and multi-band effects, which yields good agreement with experimental observations. Aspects of this model may be applied to understanding other strong-field non-perturbative phenomena in solids.

The nature and efficacy of culturally-adapted psychosocial interventions for schizophrenia: a systematic review and meta-analysis.

BACKGROUND: Evidence-based psychosocial treatments for schizophrenia founded on Western belief systems and values may not be efficacious in different cultures without adaptation. This systematic review analyses the nature and outcomes of culturally-adapted psychosocial interventions in schizophrenia, examining how interventions have been adapted, their efficacy and what features drive heterogeneity in outcome. METHOD: Articles identified by searching electronic databases from inception to 3 March 2016, reference lists and previous reviews were independently screened by two authors for eligible controlled trials. Data on the nature of adaptations was analysed inductively using thematic analyses. Meta-analyses were conducted using random effects models to calculate effect sizes (Hedges' g) for symptoms. RESULTS: Forty-six studies with 7828 participants were included, seven adapted for minority populations. Cultural adaptations were grouped into nine themes: language, concepts and illness models, family, communication, content, cultural norms and practices, context and delivery, therapeutic alliance, and treatment goals. Meta-analyses showed significant post-treatment effects in favour of adapted interventions for total symptom severity (n = 2345, g: -0.23, 95% confidence interval (CI) -0.36 to -0.09), positive (n = 1152, g: -0.56, 95% CI -0.86 to -0.26), negative (n = 855, g: -0.39, 95% CI -0.63 to -0.15), and general (n = 525, g: -0.75, CI -1.21 to -0.29) symptoms. CONCLUSIONS: The adaptation process can be described within a framework that serves as a benchmark for development or assessment of future adaptations. Culturally adapted interventions were more efficacious than usual treatment in proportion to the degree of adaptation. There is insufficient evidence to show that adapted interventions are better than non-adapted interventions. Features of context, intervention and design influenced efficacy. Investigating whether adaptation improves efficacy, most importantly amongst ethnic minorities, requires better designed trials with comparisons against unadapted interventions.

Generation of scaled protogalactic seed magnetic fields in laser-produced shock waves.

The standard model for the origin of galactic magnetic fields is through the amplification of seed fields via dynamo or turbulent processes to the level consistent with present observations. Although other mechanisms may also operate, currents from misaligned pressure and temperature gradients (the Biermann battery process) inevitably accompany the formation of galaxies in the absence of a primordial field. Driven by geometrical asymmetries in shocks associated with the collapse of protogalactic structures, the Biermann battery is believed to generate tiny seed fields to a level of about 10(-21) gauss (refs 7, 8). With the advent of high-power laser systems in the past two decades, a new area of research has opened in which, using simple scaling relations, astrophysical environments can effectively be reproduced in the laboratory. Here we report the results of an experiment that produced seed magnetic fields by the Biermann battery effect. We show that these results can be scaled to the intergalactic medium, where turbulence, acting on timescales of around 700 million years, can amplify the seed fields sufficiently to affect galaxy evolution.

Diet Supplementation with Soy Protein Isolate, but Not the Isoflavone Genistein, Protects Against Alcohol-Induced Tumor Progression in DEN-Treated Male Mice.

Diethylnitrosamine-treated male mice were assigned to 4 groups: a casein-based 35% high fat ethanol liquid diet (EtOH), an EtOH diet made with soy protein isolate protein (EtOH/SOY), an EtOH liquid diet supplemented with genistein (EtOH/GEN) and a chow group. EtOH feeding, final concentration 5% (v/v), continued for 16 wks. EtOH increased incidence and multiplicity of basophilic lesions and adenomas compared to the chow group, (p < 0.05). The EtOH/SOY group had reduced adenoma progression when compared to the EtOH and EtOH/GEN group, (p < 0.05). Genistein supplementation had no protective effect. Soy feeding significantly reduced serum ALT concentrations (p < 0.05), decreased hepatic TNFα and CD-14 expression and decreased nuclear accumulation of NFκB protein in EtOH/SOY-treated mice compared to the EtOH group (p < 0.05). With respect to ceramides, high resolution MALDI-FTICR Imaging mass spectrometry revealed changes in the accumulation of long acyl chain ceramide species, in particular C18, in the EtOH group when compared to the EtOH/SOY group. Additionally, expression of acid ceramidase and sphingosine kinase 1 which degrade ceramide into sphingosine and convert sphingosine to sphingosine-1-phosphate (S1P) respectively and expression of S1P receptors S1PR2 and S1PR3 were all upregulated by EtOH and suppressed in the EtOH/SOY group, p < 0.05. EtOH feeding also increased hepatocyte proliferation and mRNA expression of ß-catenin targets, including cyclin D1, MMP7 and glutamine synthase, which were reduced in the EtOH/SOY group, p < 0.05. These findings suggest that soy prevents tumorigenesis by reducing inflammation and by reducing hepatocyte proliferation through inhibition of EtOH-mediated ß-catenin signaling. These mechanisms may involve blockade of sphingolipid signaling.

Developed turbulence and nonlinear amplification of magnetic fields in laboratory and astrophysical plasmas.

The visible matter in the universe is turbulent and magnetized. Turbulence in galaxy clusters is produced by mergers and by jets of the central galaxies and believed responsible for the amplification of magnetic fields. We report on experiments looking at the collision of two laser-produced plasma clouds, mimicking, in the laboratory, a cluster merger event. By measuring the spectrum of the density fluctuations, we infer developed, Kolmogorov-like turbulence. From spectral line broadening, we estimate a level of turbulence consistent with turbulent heating balancing radiative cooling, as it likely does in galaxy clusters. We show that the magnetic field is amplified by turbulent motions, reaching a nonlinear regime that is a precursor to turbulent dynamo. Thus, our experiment provides a promising platform for understanding the structure of turbulence and the amplification of magnetic fields in the universe.

Periaqueductal Grey EP3 Receptors Facilitate Spinal Nociception in Arthritic Secondary Hypersensitivity.

UNLABELLED: Descending controls on spinal nociceptive processing play a pivotal role in shaping the pain experience after tissue injury. Secondary hypersensitivity develops within undamaged tissue adjacent and distant to damaged sites. Spinal neuronal pools innervating regions of secondary hypersensitivity are dominated by descending facilitation that amplifies spinal inputs from unsensitized peripheral nociceptors. Cyclooxygenase-prostaglandin (PG) E2 signaling within the ventrolateral periaqueductal gray (vlPAG) is pronociceptive in naive and acutely inflamed animals, but its contributions in more prolonged inflammation and, importantly, secondary hypersensitivity remain unknown. In naive rats, PG EP3 receptor (EP3R) antagonism in vlPAG modulated noxious withdrawal reflex (EMG) thresholds to preferential C-nociceptor, but not A-nociceptor, activation and raised thermal withdrawal thresholds in awake animals. In rats with inflammatory arthritis, secondary mechanical and thermal hypersensitivity of the hindpaw developed and was associated with spinal sensitization to A-nociceptor inputs alone. In arthritic rats, blockade of vlPAG EP3R raised EMG thresholds to C-nociceptor activation in the area of secondary hypersensitivity to a degree equivalent to that evoked by the same manipulation in naive rats. Importantly, vlPAG EP3R blockade also affected responses to A-nociceptor activation, but only in arthritic animals. We conclude that vlPAG EP3R activity exerts an equivalent facilitation on the spinal processing of C-nociceptor inputs in naive and arthritic animals, but gains in effects on spinal A-nociceptor processing from a region of secondary hypersensitivity. Therefore, the spinal sensitization to A-nociceptor inputs associated with secondary hypersensitivity is likely to be at least partly dependent on descending prostanergic facilitation from the vlPAG. SIGNIFICANCE STATEMENT: After tissue damage, sensitivity to painful stimulation develops in undamaged areas (secondary hypersensitivity). This is found in many painful conditions, particularly arthritis. The periaqueductal gray (PAG) is an important center that controls spinal nociceptive processing, on which secondary hypersensitivity depends. Prostaglandins (PGs) are mediators of inflammation with pronociceptive actions within the PAG under normal conditions. We find that secondary hindpaw hypersensitivity in arthritic rats results from spinal sensitization to peripheral A-nociceptor inputs. In the PAG of arthritic, but not naive, rats, there is enhanced control of spinal A-nociceptor processing through PG EP3 receptors. The descending facilitatory actions of intra-PAG PGs play a direct and central role in the maintenance of inflammatory secondary hypersensitivity, particularly relating to the processing of A-fiber nociceptive information.

Relativistic electron acceleration by mJ-class kHz lasers normally incident on liquid targets.

We report observation of kHz-pulsed-laser-accelerated electron energies up to 3 MeV in the -klaser (backward) direction from a 3 mJ laser interacting at normal incidence with a solid density, flowing-liquid target. The electrons/MeV/s.r. >1 MeV recorded here using a mJ-class laser exceeds or equals that of prior super-ponderomotive electron studies employing lasers at lower repetition-rates and oblique incidence. Focal intensity of the 40-fs-duration laser is 1.5 · 1018 W cm-2, corresponding to only ∼80 keV electron ponderomotive energy. Varying laser intensity confirms electron energies in the laser-reflection direction well above what might be expected from ponderomotive scaling in normal-incidence laser-target geometry. This direct, normal-incidence energy spectrum measurement is made possible by modifying the final focusing off-axis-paraboloid (OAP) mirror with a central hole that allows electrons to pass, and restoring laser intensity through adaptive optics. A Lanex-based, optics-free high-acquisition rate (>100 Hz) magnetic electron-spectrometer was developed for this study to enable shot-to-shot statistical analysis and real-time feedback, which was leveraged in finding optimal pre-plasma conditions. 3D Particle-in-cell simulations of the interaction show qualitative super-ponderomotive spectral agreement with experiment. The demonstration of a high-repetition-rate, high-flux source containing >MeV electrons from a few-mJ, 40 fs laser and a simple liquid target encourages development of future ≥kHz-repetition, fs-duration electron-beam applications.

Transition from Collisional to Collisionless Regimes in Interpenetrating Plasma Flows on the National Ignition Facility.

A study of the transition from collisional to collisionless plasma flows has been carried out at the National Ignition Facility using high Mach number (M>4) counterstreaming plasmas. In these experiments, CD-CD and CD-CH planar foils separated by 6-10 mm are irradiated with laser energies of 250 kJ per foil, generating ∼1000 km/s plasma flows. Varying the foil separation distance scales the ion density and average bulk velocity and, therefore, the ion-ion Coulomb mean free path, at the interaction region at the midplane. The characteristics of the flow interaction have been inferred from the neutrons and protons generated by deuteron-deuteron interactions and by x-ray emission from the hot, interpenetrating, and interacting plasmas. A localized burst of neutrons and bright x-ray emission near the midpoint of the counterstreaming flows was observed, suggesting strong heating and the initial stages of shock formation. As the separation of the CD-CH foils increases we observe enhanced neutron production compared to particle-in-cell simulations that include Coulomb collisions, but do not include collective collisionless plasma instabilities. The observed plasma heating and enhanced neutron production is consistent with the initial stages of collisionless shock formation, mediated by the Weibel filamentation instability.

Modafinil and cognitive enhancement in schizophrenia and healthy volunteers: the effects of test battery in a randomised controlled trial.

BACKGROUND: Cognitive deficits in schizophrenia have major functional impacts. Modafinil is a cognitive enhancer whose effect in healthy volunteers is well-described, but whose effects on the cognitive deficits of schizophrenia appear to be inconsistent. Two possible reasons for this are that cognitive test batteries vary in their sensitivity, or that the phase of illness may be important, with patients early in their illness responding better. METHODS: A double-blind, randomised, placebo-controlled single-dose crossover study of modafinil 200 mg examined this with two cognitive batteries [MATRICS Consensus Cognitive Battery (MCCB) and Cambridge Neuropsychological Test Automated Battery (CANTAB)] in 46 participants with under 3 years' duration of DSM-IV schizophrenia, on stable antipsychotic medication. In parallel, the same design was used in 28 age-, sex-, and education-matched healthy volunteers. Uncorrected p values were calculated using mixed effects models. RESULTS: In patients, modafinil significantly improved CANTAB Paired Associate Learning, non-significantly improved efficiency and significantly slowed performance of the CANTAB Stockings of Cambridge spatial planning task. There was no significant effect on any MCCB domain. In healthy volunteers, modafinil significantly increased CANTAB Rapid Visual Processing, Intra-Extra Dimensional Set Shifting and verbal recall accuracy, and MCCB social cognition performance. The only significant differences between groups were in MCCB visual learning. CONCLUSIONS: As in earlier chronic schizophrenia studies, modafinil failed to produce changes in cognition in early psychosis as measured by MCCB. CANTAB proved more sensitive to the effects of modafinil in participants with early schizophrenia and in healthy volunteers. This confirms the importance of selecting the appropriate test battery in treatment studies of cognition in schizophrenia.

In vivo imaging of brain microglial activity in antipsychotic-free and medicated schizophrenia: a [11C](R)-PK11195 positron emission tomography study.

Positron emission tomography (PET) imaging of the 18 kDa translocator protein (TSPO) has been used to investigate whether microglial activation, an indication of neuroinflammation, is evident in the brain of adults with schizophrenia. Interpretation of these studies is confounded by potential modulatory effects of antipsychotic medication on microglial activity. In the first such study in antipsychotic-free schizophrenia, we have used [11C](R)-PK11195 PET to compare TSPO availability in a predominantly antipsychotic-naive group of moderate-to-severely symptomatic unmedicated patients (n=8), similarly symptomatic medicated patients with schizophrenia taking risperidone or paliperidone by regular intramuscular injection (n=8), and healthy comparison subjects (n=16). We found no evidence for increased TSPO availability in antipsychotic-free patients compared with healthy controls (mean difference 4%, P=0.981). However, TSPO availability was significantly elevated in medicated patients (mean increase 88%, P=0.032) across prefrontal (dorsolateral, ventrolateral, orbital), anterior cingulate and parietal cortical regions. In the patients, TSPO availability was also strongly correlated with negative symptoms measured using the Positive and Negative Syndrome Scale across all the brain regions investigated (r=0.651-0.741). We conclude that the pathophysiology of schizophrenia is not associated with microglial activation in the 2-6 year period following diagnosis. The elevation in the medicated patients may be a direct effect of the antipsychotic, although this study cannot exclude treatment resistance and/or longer illness duration as potential explanations. It also remains to be determined whether it is present only in a subset of patients, represents a pro- or anti-inflammatory state, its association with primary negative symptoms, and whether there are significant differences between antipsychotics.

Few-cycle pulse laser induced damage threshold determination of ultra-broadband optics.

A systematic study of few-cycle pulse laser induced damage threshold (LIDT) determination was performed for commercially-available ultra-broadband optics, (i.e. chirped mirrors, silver mirrors, beamsplitters, etc.) in vacuum and in air, for single and multi-pulse regime (S-on-1). Multi-pulse damage morphology at fluences below the single-pulse LIDT was studied in order to investigate the mechanisms leading to the onset of damage. Stark morphological contrast was observed between multi-pulse damage sites formed in air versus those in vacuum. One effect of vacuum testing compared to air included suppression of laser-induced periodic surface structures (LIPSS) formation, possibly influenced by a reduced presence of damage debris. Another effect of vacuum was occasional lowering of LIDT, which appears to be due to the stress-strain performance of the coating design during laser irradiation and under the external stress of vacuum ambience. A fused silica substrate is also examined, and a non-LIPSS nanostructuring is observed on the surface. Possible mechanisms are discussed.

Laser induced periodic surface structure formation in germanium by strong field mid IR laser solid interaction at oblique incidence.

Laser induced periodic surface structures (LIPSS or ripples) were generated on single crystal germanium after irradiation with multiple 3 µm femtosecond laser pulses at a 45° angle of incidence. High and low spatial frequency LIPSS (HSFL and LSFL, respectively) were observed for both s- and p-polarized light. The measured LSFL period for p-polarized light was consistent with the currently established LIPSS origination model of coupling between surface plasmon polaritons (SPP) and the incident laser pulses. A vector model of SPP coupling is introduced to explain the formation of s-polarized LSFL away from the center of the damage spot. Additionally, a new method is proposed to determine the SPP propagation length from the decay in ripple depth. This is used along with the measured LSFL period to estimate the average electron density and Drude collision time of the laser-excited surface. Finally, full-wave electromagnetic simulations are used to corroborate these results while simultaneously offering insight into the nature of LSFL formation.