Connecting the dots - A systematic review on coherence analysis in dystonia.

BACKGROUND: Increased 4-12 Hz oscillatory activity in the cortico-basal ganglia-thalamo-cortical (CBGTC) loop is reported in dystonia. Coherence analysis is a measure of linear coupling between two signals, revealing oscillatory activity drives that are common across motor units. By performing coherence analysis, activity of the CBGTC-loop can be measured with modalities like local field potentials (LFPs), electromyography (EMG), and electro-encephalography (EEG). The aim of this study is to perform a systematic review on the use of coherence analysis for clinical assessment and treatment of dystonia. METHODS: A systematic review was performed on a search in Embase and PubMed on June 28th, 2023. All studies incorporating coherence analysis and an adult dystonia cohort were included. Three authors evaluated the eligibility of the articles. Quality was assessed using the QUADAS-2 checklist. RESULTS: A total of 41 articles were included, with data of 395 adult dystonia patients. In the selected records, six different types of coherence were investigated: corticocortical, corticopallidal, corticomuscular, pallidopallidal, pallidomuscular, and intermuscular coherence. Various types of 4-12 coherence were found to be increased in all dystonia subtypes. CONCLUSION: There is increased 4-12 Hz coherence found between the cortex, basal ganglia, and affected muscles in all dystonia subtypes. However, the relationship between 4-12 Hz coherence and the dystonic clinical state has not been established. DBS treatment leads to a reduction of 4-12 Hz coherence. In combination with the results of this review, the 4-12 Hz frequency band can be used as a promising phenomenon for the development of a biomarker.

A Pfs48/45-based vaccine to block Plasmodium falciparum transmission: phase 1, open-label, clinical trial.

BACKGROUND: The stalling global progress in malaria control highlights the need for novel tools for malaria elimination, including transmission-blocking vaccines. Transmission-blocking vaccines aim to induce human antibodies that block parasite development in the mosquito and mosquitoes becoming infectious. The Pfs48/45 protein is a leading Plasmodium falciparum transmission-blocking vaccine candidate. The R0.6C fusion protein, consisting of Pfs48/45 domain 3 (6C) and the N-terminal region of P. falciparum glutamate-rich protein (R0), has previously been produced in Lactococcus lactis and elicited functional antibodies in rodents. Here, we assess the safety and transmission-reducing efficacy of R0.6C adsorbed to aluminium hydroxide with and without Matrix-M™ adjuvant in humans. METHODS: In this first-in-human, open-label clinical trial, malaria-naïve adults, aged 18-55 years, were recruited at the Radboudumc in Nijmegen, the Netherlands. Participants received four intramuscular vaccinations on days 0, 28, 56 and 168 with either 30 µg or 100 µg of R0.6C and were randomised for the allocation of one of the two different adjuvant combinations: aluminium hydroxide alone, or aluminium hydroxide combined with Matrix-M1™ adjuvant. Adverse events were recorded from inclusion until 84 days after the fourth vaccination. Anti-R0.6C and anti-6C IgG titres were measured by enzyme-linked immunosorbent assay. Transmission-reducing activity of participants' serum and purified vaccine-specific immunoglobulin G was assessed by standard membrane feeding assays using laboratory-reared Anopheles stephensi mosquitoes and cultured P. falciparum gametocytes. RESULTS: Thirty-one participants completed four vaccinations and were included in the analysis. Administration of all doses was safe and well-tolerated, with one related grade 3 adverse event (transient fever) and no serious adverse events occurring. Anti-R0.6C and anti-6C IgG titres were similar between the 30 and 100 µg R0.6C arms, but higher in Matrix-M1™ arms. Neat participant sera did not induce significant transmission-reducing activity in mosquito feeding experiments, but concentrated vaccine-specific IgGs purified from sera collected two weeks after the fourth vaccination achieved up to 99% transmission-reducing activity. CONCLUSIONS: R0.6C/aluminium hydroxide with or without Matrix-M1™ is safe, immunogenic and induces functional Pfs48/45-specific transmission-blocking antibodies, albeit at insufficient serum concentrations to result in transmission reduction by neat serum. Future work should focus on identifying alternative vaccine formulations or regimens that enhance functional antibody responses. TRIAL REGISTRATION: The trial is registered with ClinicalTrials.gov under identifier NCT04862416.

Oral health assessment in institutionalized elderly: a scoping review.

When elderly become frail and in need for complex care, they can no longer live independently at home and may be admitted to nursing homes. Various studies have shown that oral health in this population is remarkably poor, which may lead to distressing situations and impacts quality of life. A variety of definitions or descriptions for oral health is used. Without a uniform parameter, it is impossible to determine whether oral health in institutionalized elderly is actually improving or deteriorating over time, as well as the effect of (preventive) interventions. In search for an adequate and clinically applicable parameter to determine oral health in this specific patient group, this scoping review aims to give an overview of the currently used parameters for determining oral health in institutionalized elderly. Ninety different parameters were identified, and 50 parameters were solely used by one study. Only 4 parameters were frequently used (in > 20 studies). The relevance of these parameters for this specific patient group is discussed. To aid the planning and commissioning of future research and patient care, there is an urgent need for an adequate and uniform parameter for oral health determination in institutionalized elderly.

[Whether or not to remove root remnants in frail older adults?] / Wel of niet wortelresten verwijderen bij kwetsbare ouderen?

Many frail older adults have a poor oral health: unrestorable broken teeth and root remnants with open root canals, commonly associated with periapical and periodontal inflammation, are often seen. Improving oral health in this growing group of frail older adults is a considerable challenge for dental care professionals. Dentists are often uncertain how to deal with root remnants and unrestorable broken teeth in psychogeriatric and/or medically compromised frail older adults. Decisions about the extraction or retention of root remnants should not only be made on the basis of preventing pain and inflammation, but also on the course of disease, life expectancy, cooperation, laws and regulations and other factors that are an issue in geriatric patients but not in regular (healthy) patients. To help oral health care professionals in their treatment choice for this complex patient group, a decision tree was developed in which both root and patient-related factors were included.

Time-lapse imaging of human embryos fertilized with testicular sperm reveals an impact on the first embryonic cell cycle.

Testicular sperm is increasingly used during in vitro fertilization treatment. Testicular sperm has the ability to fertilize the oocyte after intracytoplasmic sperm injection (ICSI), but they have not undergone maturation during epididymal transport. Testicular sperm differs from ejaculated sperm in terms of chromatin maturity, incidence of DNA damage, and RNA content. It is not fully understood what the biological impact is of using testicular sperm, on fertilization, preimplantation embryo development, and postimplantation development. Our goal was to investigate differences in human preimplantation embryo development after ICSI using testicular sperm (TESE-ICSI) and ejaculated sperm. We used time-lapse embryo culture to study these possible differences. Embryos (n = 639) originating from 208 couples undergoing TESE-ICSI treatment were studied and compared to embryos (n = 866) originating from 243 couples undergoing ICSI treatment with ejaculated sperm. Using statistical analysis with linear mixed models, we observed that pronuclei appeared 0.55 h earlier in TESE-ICSI embryos, after which the pronuclear stage lasted 0.55 h longer. Also, significantly more TESE-ICSI embryos showed direct unequal cleavage from the 1-cell stage to the 3-cell stage. TESE-ICSI embryos proceeded faster through the cleavage divisions to the 5- and the 6-cell stage, but this effect disappeared when we adjusted our model for maternal factors. In conclusion, sperm origin affects embryo development during the first embryonic cell cycle, but not developmental kinetics to the 8-cell stage. Our results provide insight into the biological differences between testicular and ejaculated sperm and their impact during human fertilization.

[Lifetime dental care: treatment for periodontally affected elderly]. / Levensloopbestendig behandelen van de oudere met parodontitis.

Although many elderly remain healthy to an advanced age, apparently healthy and robust elderly can quickly become frail as a result of physical or psychological events. With frailty, oral health can quickly deteriorate and treatment is often difficult, with possible consequences for general health and quality of life. To prevent treatment dilemma's at an advanced age, it is advisable to think ahead when making a treatment plan for older patients and to aim for a surveyable oral situation, so in case of illness or care dependency, oral health can be maintained relatively easily. This so-called 'lifetime' dental treatment plan takes into account the various areas of frailty (physical, psychological and social), is predictable and can be modified, and takes life expectancy and general health into consideration. Lifetime dental treatment for the elderly, specifically the periodontally affected, has as yet rarely been discussed in the literature. This article represents a view of such treatment on the basis of clinical expertise.

Career development in fragment-based drug discovery.

The pharmaceutical industry is highly reliant on researchers who not only possess the technical knowledge but also the professional skills to collaborate in drug development. To prepare future practitioners to thrive in this interdisciplinary environment, Innovative Training Networks (ITNs) have become increasingly important in doctoral training. In this piece, we explore the benefits of these ITNs in training future practitioners in drug discovery. Through a bibliometric review, we find that the top researchers in fragment-based drug discovery have a high degree of collaboration and mobility across institutes. We then investigate which aspects of the ITN training program enable PhD students to gain these skills. We find that secondments, the short-term stays that students have in partner research institutes, are useful in preparing students to have both broad knowledge of drug discovery and specialization in their field of interest. Aside from imparting technical skills, we find that the collaborative environment in ITNs enables students to communicate better and to work effectively in teams. Doctoral students benefit by being exposed to relevant experiences that they can later apply as they navigate through the complex web of relationships and competencies in the industry. We conclude by recommending best practices to further improve ITNs in the training of future practitioners.

[Clinical characteristics of sexually abused individuals with borderline intellectual functioning or mild intellectual disability: an overview of the literature]. / Klinische kenmerken van seksueel misbruikte mensen met een lichte verstandelijke beperking: een literatuuroverzicht.

BACKGROUND: Sexual abuse in individuals with (above) average iq is associated with a wide range of behavioural and psychological clinical characteristics, including characteristics regarding body experience. However, research on the clinical characteristics of sexually abused individuals with borderline intellectual functioning or mild intellectual disability (bif-mid) is scarce. OBJECTIVE To provide an overview of the literature on the clinical characteristics of sexually abused individuals with bif-mid.
METHOD: PubMed, Embase, PsycInfo, cinahl, Cochrane Library and Web of Science were searched for relevant publications using terms related to 'intellectual disability' and 'sexual abuse'.
RESULTS: Seven studies were included. The studies in question mostly reported behavioural and psychological characteristics such as challenging behaviour, sexualised behaviour or posttraumatic stress, anxiety or depressive symptoms associated with sexual abuse in individuals with bif-mid. None of the studies reported problems regarding body experience. CONCLUSIONS Sexual abuse in individuals with bif-mid is associated with a broad range of behavioural and psychological characteristics similar to that of individuals with (above) average iq. Whether sexually abused individuals with bif-mid have similar problems in body experience as sexually abused individuals with (higher than) average iq needs to be investigated.

Body ownership and the absence of touch: approaching the rubber hand inside and outside peri-hand space.

It is widely accepted that the integration of visual and tactile information is a necessity to induce ownership over a rubber hand. This idea has recently been challenged by Ferri et al. (Proc R Soc B 280:1-7, 2013), as they found that sense of ownership was evident by mere expectation of touch. In our study, we aimed to further investigate this finding, by studying whether the mere potential for touch yields a sense of ownership similar in magnitude to that resulting from actually being touched. We conducted two experiments. In the first experiment, our set-up was the classical horizontal set-up (similar to Botvinick and Cohen, Nature 391:756, 1998). Sixty-three individuals were included and performed the classical conditions (synchronous, asynchronous), an approached but not touched (potential for touch), and a 'visual only' condition. In the second experiment, we controlled for differences between the current set-up and the vertical set-up used by Ferri et al. (Proc R Soc B 280:1-7, 2013). Fifteen individuals were included and performed a synchronous and various approaching conditions [i.e., vertical approach, horizontal approach, and a control approach (no hands)]. In our first experiment, we found that approaching the rubber hand neither induced a larger proprioceptive drift nor a stronger subjective sense of ownership than asynchronous stimulation did. Generally, our participants gained most sense of ownership in the synchronous condition, followed by the visual only condition. When using a vertical set-up (second experiment), we confirmed previous suggestions that tactile expectation was able to induce embodiment over a foreign hand, similar in magnitude to actual touch, but only when the real and rubber hand were aligned on the vertical axis, thus along the trajectory of the approaching stimulus. These results indicate that our brain uses bottom-up sensory information, as well as top-down predictions for building a representation of our body.

Body representation does not lag behind in updating for the pubertal growth spurt.

Both making perceptual judgments about your own body and successfully moving your body through the world depend on a mental representation of the body. However, there are indications that moving might be challenging when your body is changing. For instance, the pubertal growth spurt has been reported to be negatively correlated to motor competence. A possible explanation for this clumsiness would be that when the body is growing fast, updating the body representation may lag behind, resulting in a mismatch between internal body representation and actual body size. The current study investigated this hypothesis by testing participants ranging from aged 6 to 50 years on both a tactile body image task and a motor body schema task. Separate groups of participants, including those in the age range when pubertal growth spurt occurs, were asked to estimate the distance between two simultaneously applied tactile stimuli on the arm and to move their hand through apertures of different widths. Tactile distance estimations were equal between participants before, during, and after the age range where the pubertal growth spurt is expected. Similarly, Bayesian evaluation of informative hypotheses showed that participants in the age range of the growth spurt did not move through the apertures as if their representation of the hand was smaller than its physical size. These results suggest that body representations do not lag behind in updating for the pubertal growth spurt.

The influence of gender concordance between general practitioner and patient on antibiotic prescribing for sore throat symptoms: a retrospective study.

BACKGROUND: Patient gender as well as doctor gender are known to affect doctor-patient interaction during a medical consultation. It is however not known whether an interaction of gender influences antibiotic prescribing. This study examined GP's prescribing behavior of antibiotics at the first presentation of patients with sore throat symptoms in primary care. We investigated whether GP gender, patient gender and gender concordance have an effect on the GP's prescribing behavior of antibiotics in protocolled and non-protocolled diagnoses. METHODS: We analyzed electronic health record data of 11,285 GP practice consultations in the Netherlands in 2013 extracted from the Nivel Primary Care Database. Our primary outcome was the prescription of antibiotics for throat symptoms. Sore throat symptoms were split up in 'protocolled diagnoses' and 'non-protocolled diagnoses'. The association between gender concordance and antibiotic prescription was estimated with multilevel regression models that controlled for patient age and comorbidity. RESULTS: Antibiotic prescription was found to be lower among female GPs (OR 0.88, CI 95% 0.67-1.09; p = .265) and female patients (OR 0.93, 95% 0.84-1.02; p = .142), but observed differences were not statistically significant. The difference in prescription rates by gender concordance were small and not statistically significant in non-protocolled consultations (OR 0.92, OR 95% CI: 0.83-1.01; p = .099), protocolled consultations (OR 1.00, OR 95% CI: 0.68-1.32; p = .996) and all GP practice consultations together (OR 0.92, OR 95% CI: 0.82-1.02; p = .118). Within the female GP group, however, gender concordance was associated with reduced prescribing of antibiotics (OR 0.85, OR 95% CI: 0.72-0.99; p = 0.034). CONCLUSIONS: In this study, female GPs prescribed antibiotics less often than male GPs, especially in consultation with female patients. This study shows that, in spite of clinical guidelines, gender interaction may influence the prescription of antibiotics with sore throat symptoms.

Prevalence of the AMHR2 mutation in Miniature Schnauzers and genetic investigation of a Belgian Malinois with persistent Müllerian duct syndrome.

Persistent Müllerian duct syndrome (PMDS) is a sex-limited disorder in which males develop portions of the female reproductive tract. Important consequences of PMDS are cryptorchidism and its sequelae of infertility and increased risk of testicular cancer. Anti-Müllerian hormone (AMH) and its receptor (AMHR2) induce the regression of the Müllerian ducts in male embryos. In Miniature Schnauzer dogs, the genetic basis has been identified as an autosomal recessive nonsense mutation in AMHR2, but the allele frequency of the mutation is unknown. Thus, the primary objective of this study was to estimate the prevalence of the AMHR2 mutation in North American Miniature Schnauzers, in order to ascertain the value of genetic testing in this breed. An additional objective was to determine whether mutations in AMH or AMHR2 were responsible for PMDS in a Belgian Malinois; this would aid development of a genetic test for the Belgian Malinois breed. Genomic DNA from 216 Miniature Schnauzers (including one known PMDS case) was genotyped for the AMHR2 mutation, and DNA from a single PMDS-affected Belgian Malinois was sequenced for all coding exons of AMH and AMHR2. The Miniature Schnauzer cohort had an AMHR2 mutation allele frequency of 0.16 and a carrier genotypic frequency of 0.27. The genetic basis for PMDS in the Belgian Malinois was not determined, as no coding or splicing mutations were identified in either AMH or AMHR2. These findings support a benefit to AMHR2 mutation testing Miniature Schnauzers used for breeding or with cryptorchidism.

Ultralow Surface Recombination Velocity in Passivated InGaAs/InP Nanopillars.

The III-V semiconductor InGaAs is a key material for photonics because it provides optical emission and absorption in the 1.55 µm telecommunication wavelength window. However, InGaAs suffers from pronounced nonradiative effects associated with its surface states, which affect the performance of nanophotonic devices for optical interconnects, namely nanolasers and nanodetectors. This work reports the strong suppression of surface recombination of undoped InGaAs/InP nanostructured semiconductor pillars using a combination of ammonium sulfide, (NH4)2S, chemical treatment and silicon oxide, SiOx, coating. An 80-fold enhancement in the photoluminescence (PL) intensity of submicrometer pillars at a wavelength of 1550 nm is observed as compared with the unpassivated nanopillars. The PL decay time of ∼0.3 µm wide square nanopillars is dramatically increased from ∼100 ps to ∼25 ns after sulfur treatment and SiOx coating. The extremely long lifetimes reported here, to our knowledge the highest reported to date for undoped InGaAs nanostructures, are associated with a record-low surface recombination velocity of ∼260 cm/s. We also conclusively show that the SiOx capping layer plays an active role in the passivation. These results are crucial for the future development of high-performance nanoscale optoelectronic devices for applications in energy-efficient data optical links, single-photon sensing, and photovoltaics.

The relationship between the dopaminergic system and depressive symptoms in cervical dystonia.

PURPOSE: Cervical dystonia (CD) is associated with tremor/jerks (50%) and psychiatric complaints (17-70%). The dopaminergic system has been implicated in the pathophysiology of CD in animal and imaging studies. Dopamine may be related to the motor as well as non-motor symptoms of CD. CD is associated with reduced striatal dopamine D2/3 (D2/3) receptor and increased dopamine transporter (DAT) binding. There are differences in the dopamine system between CD patients with and without jerks/tremor and psychiatric symptoms. METHODS: Patients with CD and healthy controls underwent neurological and psychiatric examinations. Striatal DAT and D2/3 receptor binding were assessed using [123I]FP-CIT and [123I]IBZM SPECT, respectively. The ratio of specific striatal to non-specific binding (binding potential; BPND) was the outcome measure. RESULTS: Twenty-seven patients with CD and 15 matched controls were included. Nineteen percent of patients fulfilled the criteria for a depression. Striatal DAT BPND was significantly lower in depressed versus non-depressed CD patients. Higher DAT BPND correlated significantly with higher scores on the Unified Myoclonus Rating Scale (UMRS). The striatal D2/3 receptor BPND in CD patients showed a trend towards lower binding compared to controls. The D2/3 BPND was significantly lower in depressed versus non-depressed CD patients. A significant correlation between DAT and D2/3R BPND was found in both in patients and controls. CONCLUSIONS: Alterations of striatal DAT and D2/3 receptor binding in CD patients are related mainly to depression. DAT BPND correlates significantly with scores on the UMRS, suggesting a role for dopamine in the pathophysiology of tremor/jerks in CD.

Laterality and body ownership: Effect of handedness on experience of the rubber hand illusion.

Body ownership has mainly been linked to the right hemisphere and larger interhemispheric connectivity has been shown to be associated with greater right hemispheric activation. Mixed-handed participants tend to have more interhemispheric connectivity compared to extreme handed participants. The aim of this study was to examine whether feelings of ownership as assessed with the rubber hand illusion (RHI) are differentiated by handedness and differed between the left and right hand. Sinistrals-, dextrals-, and mixed-handed individuals (n = 63) were subjected to the RHI. Stroking was synchronously and asynchronously performed on both the participant's hand and a rubber hand. Outcome measures were an embodiment questionnaire and proprioceptive drift. In contrast to our hypotheses we show a similar experience of ownership for all groups, which may indicate no hemispheric specialization for the illusion. In addition, plasticity of ownership and body ownership are similar for the left hand and right hand in all participants, which suggests similar representations for both hands in the brain. This might be useful to maintain a coherent sense of the body in space.

High-bandwidth uni-traveling carrier waveguide photodetector on an InP-membrane-on-silicon platform.

A uni-traveling carrier photodetector (UTC-PD), heterogeneously integrated on silicon, is demonstrated. It is fabricated in an InP-based photonic membrane bonded on a silicon wafer, using a novel double-sided processing scheme. A very high 3 dB bandwidth of beyond 67 GHz is obtained, together with a responsivity of 0.7 A/W at 1.55 µm wavelength. In addition, open eye diagrams at 54 Gb/s are observed. These results promise high speed applications using a novel full-functionality photonic platform on silicon.

III-V-on-silicon integrated micro - spectrometer for the 3 µm wavelength range.

A compact (1.2 mm2) fully integrated mid-IR spectrometer operating in the 3 µm wavelength range is presented. To our knowledge this is the longest wavelength integrated spectrometer operating in the important wavelength window for spectroscopy of organic compounds. The spectrometer is based on a silicon-on-insulator arrayed waveguide grating filter. An array of InAs0.91Sb0.09 p-i-n photodiodes is heterogeneously integrated on the spectrometers output grating couplers using adhesive bonding. The spectrometer insertion loss is less than 3 dB and the waveguide-referred responsivity of the integrated photodiodes at room temperature is 0.3 A/W.

Abdominal Compartment Syndrome and Intra-abdominal Ischemia in Patients with Severe Acute Pancreatitis.

INTRODUCTION: Severe acute pancreatitis may be complicated by intra-abdominal hypertension (IAH), abdominal compartment syndrome (ACS), and intestinal ischemia. The aim of this retrospective study is to describe the incidence, treatment, and outcome of patients with severe acute pancreatitis and ACS, in particular the occurrence of intestinal ischemia. METHODS: The medical records of all patients admitted with severe acute pancreatitis admitted to the ICU of a tertiary referral center were reviewed. The criteria proposed by the World Society of the Abdominal Compartment Syndrome (WSACS) were used to determine whether patients had IAH or ACS. RESULTS: Fifty-nine patients with severe acute pancreatitis were identified. Intra-abdominal pressure (IAP) measurements were performed in 29 patients (49.2 %). IAH was present in all patients (29/29). ACS developed in 13/29 (44.8 %) patients. Ten patients with ACS underwent decompressive laparotomy. A large proportion of patients with ACS had intra-abdominal ischemia upon laparotomy: 8/13 (61.5 %). Mortality was high in both the ACS group and the IAH group. CONCLUSION: This study confirms that ACS is common in severe acute pancreatitis. Intra-abdominal ischemia occurs in a large proportion of patients with ACS. Swift surgical intervention may be indicated when conservative measures fail in patients with ACS. National and international guidelines need to be updated so that routine IAP measurements become standard of care for patients with severe acute pancreatitis in the ICU.

G Protein-Coupled Receptor Signaling Networks from a Systems Perspective.

The signal-transduction network of a mammalian cell integrates internal and external cues to initiate adaptive responses. Among the cell-surface receptors are the G protein-coupled receptors (GPCRs), which have remarkable signal-integrating capabilities. Binding of extracellular signals stabilizes intracellular-domain conformations that selectively activate intracellular proteins. Hereby, multiple signaling routes are activated simultaneously to degrees that are signal-combination dependent. Systems-biology studies indicate that signaling networks have emergent processing capabilities that go far beyond those of single proteins. Such networks are spatiotemporally organized and capable of gradual, oscillatory, all-or-none, and subpopulation-generating responses. Protein-protein interactions, generating feedback and feedforward circuitry, are generally required for these spatiotemporal phenomena. Understanding of information processing by signaling networks therefore requires network theories in addition to biochemical and biophysical concepts. Here we review some of the key signaling systems behaviors that have been discovered recurrently across signaling networks. We emphasize the role of GPCRs, so far underappreciated receptors in systems-biology research.

Coupled cavity laser based on anti-resonant imaging via multimode interference.

We report the experimental demonstration of two coupled laser cavities via self-imaging interference in a multimode waveguide. The coupling is optimized by considering images formed by two coherent phase-delayed signals at the input of a 3×3 splitter. As a result, the complex transfer coefficients of the coupling element can be chosen to increase the mode selectivity of the coupled system. A demonstration is given by the successful fabrication of a tunable laser with a side-mode suppression ratio (SMSR) up to 40 dB and a 6.5 nm tuning range. The laser delivers milliwatts of output power to a lensed fiber and is fully compatible with processes supporting vertically-etched sidewalls.