Long-Term Observation of SARS-CoV-2 Vaccination Response upon High Efficacy Treatment in Multiple Sclerosis-A Real-World Scenario.

Immunomodulatory and immunosuppressive therapy is needed in people with a chronic neuroinflammatory disease of the central nervous system such as multiple sclerosis (MS). Therefore, MS requires monitoring for and preventing against infectious diseases like SARS-CoV-2. Vaccination and anti-viral treatments are, in particular, recommended for elderly people and people at risk of a severe course of infection and of MS. Here, we asked whether repetitive infection or vaccination influenced responses upon receiving high efficacy treatments, namely sphingosine-1-phosphate receptor modulator (S1P) or anti-CD20 B cell antibody (anti-CD20) treatments. We performed a prospective real-world study of people with MS (pwMS) under S1P or anti-CD20 with repetitive exposure to the SARS-CoV-2 virus or vaccine. The measurement of anti-SARS-CoV-2 antibody titres was performed by two independent immunoassays after initial immunisation and after booster vaccination or infection. Other laboratory and clinical parameters were included in the analysis of influencing factors. As secondary outcomes, lymphocyte and immunoglobulin levels were observed longitudinally under intravenous and subcutaneous anti-CD20 treatment. In a long-term real-world cohort of 201 pwMS, we found that despite lymphopenia upon S1P drugs, the SARS-CoV-2 immunisation response increased both in selective and non-selective S1P (100% and 88% seroconversion, respectively), whereas those under anti-CD20 therapies merely exhibited a slight long-term increase in antibody titres (52% seroconversion). The latter was independent of immunoglobulin or total lymphocyte levels, which mostly remained stable. If the individual was immunised prior to therapy initiation, their levels of SARS-CoV-2 antibodies remained high under treatment. PwMS under non-selective S1P benefit from repetitive vaccination. The risk of an insufficient vaccination response mirrored by lower SARS-CoV-2 antibodies remains in pwMS receiving anti-CD20 treatment, even after repetitive exposure to the vaccine or virus. Due to the compromised vaccination response in CD20-depleting drugs, prompt antiviral treatment might be necessary.

Seawater physics and chemistry along the Med-SHIP transects in the Mediterranean Sea in 2016.

The Mediterranean Sea has been sampled irregularly by research vessels in the past, mostly by national expeditions in regional waters. To monitor the hydrographic, biogeochemical and circulation changes in the Mediterranean Sea, a systematic repeat oceanographic survey programme called Med-SHIP was recommended by the Mediterranean Science Commission (CIESM) in 2011, as part of the Global Ocean Ship-based Hydrographic Investigations Program (GO-SHIP). Med-SHIP consists of zonal and meridional surveys with different frequencies, where comprehensive physical and biogeochemical properties are measured with the highest international standards. The first zonal survey was done in 2011 and repeated in 2018. In addition, a network of meridional (and other key) hydrographic sections were designed: the first cycle of these sections was completed in 2016, with three cruises funded by the EU project EUROFLEETS2. This paper presents the physical and chemical data of the meridional and key transects in the Western and Eastern Mediterranean Sea collected during those cruises.

Studying serum neurofilament light chain levels as a potential new biomarker for small fiber neuropathy.

BACKGROUND AND PURPOSE: Diagnosing small fiber neuropathies can be challenging. To address this issue, whether serum neurofilament light chain (sNfL) could serve as a potential biomarker of damage to epidermal Aδ- and C-fibers was tested. METHODS: Serum NfL levels were assessed in 30 patients diagnosed with small fiber neuropathy and were compared to a control group of 19 healthy individuals. Electrophysiological studies, quantitative sensory testing and quantification of intraepidermal nerve fiber density after skin biopsy were performed in both the proximal and distal leg. RESULTS: Serum NfL levels were not increased in patients with small fiber neuropathy compared to healthy controls (9.1 ± 3.9 and 9.4 ± 3.8, p = 0.83) and did not correlate with intraepidermal nerve fiber density at the lateral calf or lateral thigh or with other parameters of small fiber impairment. CONCLUSION: Serum NfL levels cannot serve as a biomarker for small fiber damage.

Case Report: Balancing immune responses - multiple sclerosis disease exacerbation under BRAF/MEK treatment for malignant melanoma.

Background: Combination treatment with BRAF/MEK inhibitors favorably impact progression-free survival in malignant melanoma. However, it may cause paradoxical activation of the MAPK/ERK pathway in immune cells without BRAF mutation, which may lead to over activation of the immune system, especially in patients with pre-existing autoimmune conditions. In this case report, treatment of malignant melanoma with BRAF/MEK inhibitors was associated with radiological disease exacerbation of pre-existing multiple sclerosis (MS). Case presentation: A 47-year-old patient with pre-existing MS was diagnosed with malignant melanoma in June 2020. Anti-tumor treatment was initiated with a combination therapy of BRAF inhibitor dabrafenib and MEK inhibitor trametinib. In February 2022, the patient presented at our neurological clinic after routine MRI revealed exacerbation of radiological MS disease activity with ten new and gadolinium-enhancing lesions, and concomitant high levels of neurofilament light chain (NfL) in serum, a marker for axonal damage. In-depth analysis of immune cells in both peripheral blood and cerebrospinal fluid was performed by multi-color flow cytometry. After treatment with the B cell-depleting antibody ocrelizumab, MS disease stability was obtained and anti-tumor medication could be continued. Conclusions: Immunomodulatory treatment in cancer patients is highly effective from an oncological point of view, but may be associated with autoimmune side effects. This is of special importance in patients with pre-existing autoimmune diseases, as reflected by our case of MS disease reactivation under treatment with BRAF/MEK inhibitors. In our case, sequential modulation of immune cell subsets by B cell depletion, associated with marked shifts in B and T cell subsets, allowed for stabilization of disease and continuation of anti-tumor treatment.

Third Stereotactic Radiosurgery for Residual Arteriovenous Malformations: A Retrospective Multicenter Study.

BACKGROUND AND OBJECTIVES: There are no studies evaluating the efficacy and safety of more than 2 stereotactic radiosurgery (SRS) procedures for cerebral arteriovenous malformations (AVM). The aim of this study was to provide evidence on the role of third single-session SRS for AVM residual. METHODS: This multicenter, retrospective study included patients managed with a third single-session SRS procedure for an AVM residual. The primary study outcome was defined as AVM nidus obliteration without AVM bleeding or symptomatic radiation-induced changes (RIC). Secondary outcomes evaluated were AVM obliteration, AVM hemorrhage, asymptomatic, and symptomatic RIC. RESULTS: Thirty-eight patients (20/38 [52.6%] females, median age at third SRS 34.5 [IQR 20] years) were included. The median clinical follow-up was 46 (IQR 14.8) months, and 17/38 (44.7%) patients achieved favorable outcome. The 3-year and 5-year cumulative probability rates of favorable outcome were 23% (95% CI = 10%-38%) and 53% (95% CI = 29%-73%), respectively. The cumulative probability of AVM obliteration at 3 and 5 years after the third SRS was 23% (95% CI = 10%-37%) and 54% (95% CI = 29%-74%), respectively. AVM bleeding occurred in 2 patients, and 1 of them underwent subsequent resection. The cumulative probability rate of post-SRS AVM hemorrhage remained constant at 5.3% (95% CI = 1%-16%) during the first 5 years of follow-up. Transient symptomatic RIC managed conservatively occurred in 5/38 patients (13.2%) at a median time of 12.5 (IQR 22.5) months from third SRS. Radiation-induced cyst formation was noted in 1 patient (4.2%) 19 months post-SRS. No mortality, radiation-associated malignancy, or permanent symptomatic RIC was noted during follow-up. CONCLUSION: A third single-session SRS to treat a residual intracranial AVM offers obliteration in most patients. The risk of RIC was low, and these effects were transient. While not often required, a third SRS can be performed in patients with persistent residual AVMs.

Surface-Guided Radiotherapy: Can We Move on from the Era of Three-Point Markers to the New Era of Thousands of Points?

The surface-guided radiotherapy (SGRT) technique improves patient positioning with submillimeter accuracy compared with the conventional positioning technique of lasers using three-point tattoos. SGRT provides solutions to considerations that arise from the conventional setup technique, such as variability in tattoo position and the psychological impact of the tattoos. Moreover, SGRT provides monitoring of intrafractional motion. PURPOSE: This literature review covers the basics of SGRT systems and examines whether SGRT can replace the traditional positioning technique. In addition, it investigates SGRT's potential in reducing positioning times, factors affecting SGRT accuracy, the effectiveness of live monitoring, and the impact on patient dosage. MATERIALS AND METHODS: This study focused on papers published from 2016 onward that compared SGRT with the traditional positioning technique and investigated factors affecting SGRT accuracy and effectiveness. RESULTS/CONCLUSIONS: SGRT provides the same or better results regarding patient positioning. The implementation of SGRT can reduce overall treatment time. It is an effective technique for detecting intrafraction patient motion, improving treatment accuracy and precision, and creating a safe and comfortable environment for the patient during treatment.

Targeting Neutrophil Extracellular Traps for Stroke Prognosis: A Promising Path.

Stroke has become the first cause of functional disability and one of the leading causes of mortality worldwide. Therefore, it is of crucial importance to develop accurate biomarkers to assess stroke risk and prognosis. Emerging evidence suggests that neutrophil extracellular trap (NET) levels may serve as a valuable biomarker to predict stroke occurrence and functional outcome. NETs are known to create a procoagulant state by serving as a scaffold for tissue factor (TF) and platelets inducing thrombosis by activating coagulation pathways and endothelium. A literature search was conducted in two databases (MEDLINE and Scopus) to trace all relevant studies published between 1 January 2016 and 31 December 2022, addressing the potential utility of NETs as a stroke biomarker. Only full-text articles in English were included. The current review includes thirty-three papers. Elevated NET levels in plasma and thrombi seem to be associated with increased mortality and worse functional outcomes in stroke, with all acute ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage included. Additionally, higher NET levels seem to correlate with worse outcomes after recanalization therapies and are more frequently found in strokes of cardioembolic or cryptogenic origin. Additionally, total neutrophil count in plasma seems also to correlate with stroke severity. Overall, NETs may be a promising predictive tool to assess stroke severity, functional outcome, and response to recanalization therapies.

Strict blood pressure control following thrombectomy is associated with neuronal injury and poor functional outcome.

OBJECTIVE: Mechanical thrombectomy (MT) has become standard treatment in acute ischemic stroke due to large vessel occlusion (LVO). However, optimal blood pressure (BP) management following successful recanalization remains unclear. We aim to investigate the association of strictly achieving BP targets of ≤160/90 mmHg with the extent of neuronal loss and functional outcome. METHODS: In patients prospectively enrolled in the Gutenberg-Stroke-Study (May 2018-November 2019), BP was measured half-hourly for 24 h following MT. Based on achieving BP target of ≤160/90 mmHg, patients with successful recanalization of LVO were divided into "low-BP" group (BP ≤ 160/90 mmHg) or "high-BP" group (BP > 160/90 mmHg). Neuronal loss was quantified by serum-based measurement of neurofilament light chain (sNfL) after three days. BP groups and association of BP parameters with sNfL were investigated by correlation analyses and multiple regression modeling. RESULTS: Of 253 enrolled patients (mean age 73.1 ± 12.9 years, 53.4% female), 165 met inclusion criteria. 21.2% (n = 35) strictly achieved "low-BP" target. "low-BP" was associated with unfavorable functional outcome at 90-day follow-up (aOR [95%CI]: 5.88 [1.88-18.32], p = 0.002) and decreased health-related quality of life (mean EQ-5D-index 0.45 ± 0.28 vs 0.63 ± 0.31, p = 0.009). sNfL levels were increased in "low-BP" patients (median [IQR] 239.7 [168.4-303.4] vs 118.8 [52.5-220.5] pg/mL, p = 0.026). Hypotensive episodes were more frequent in the "low-BP" group (48.6% vs 29.2%, p = 0.031). sNfL level could identify patients who had experienced hypotensive episodes with high discriminative ability (AUC [95%CI]: 0.68 [0.56-0.78], p = 0.007). INTERPRETATION: Strict BP control (≤160/90 mmHg) within 24 h following successful recanalization of LVO by MT is associated with increased neuronal injury, displayed by higher sNfL levels, and poorer functional outcome, potentially indicating hypotension-induced neuronal loss during post-MT phase.

Nanoparticle-Imprinted Silica Gel for the Size-Selective Capture of Silver Ultrafine Nanoparticles from Water.

A synthetic approach has been developed to prepare silica gel monoliths that embed well separated silver or gold spherical nanoparticles (NP), with diameters of 8, 18 and 115 nm. Fe3+, O2/cysteine and HNO3 were all successfully used to oxidize and remove silver NP from silica, while aqua regia was necessary for gold NP. In all cases, NP-imprinted silica gel materials were obtained, with spherical voids of the same dimensions of the dissolved particles. By grinding the monoliths, we prepared NP-imprinted silica powders that were able to efficiently reuptake silver ultrafine NP (Ag-ufNP, d = 8 nm) from aqueous solutions. Moreover, the NP-imprinted silica powders showed a remarkable size selectivity, based on the best match between NP radius and the curvature radius of the cavities, driven by the optimization of attractive Van der Waals forces between SiO2 and NP. Ag-ufNP are increasingly used in products, goods, medical devices, disinfectants, and their consequent diffusion in the environment is of rising concern. Although limited here to a proof-of-concept level, the materials and methods described in this paper may be an efficient solution for capturing Ag-ufNP from environmental waters and to safely dispose them.

Craniospinal Irradiation: A Dosimetric Comparison Between O-Ring Linac and Conventional C-arm Linac.

Purpose: The aim of this study was to perform a dosimetric evaluation between craniospinal irradiation volumetric modulated arc therapy plans designed for an O-Ring and a conventional C-arm Linac. Methods and Materials: Two adult patients were selected for this study. Two plans were designed one for a TrueBeam Edge and one for Halcyon O-ring Linac for each patient. The evaluation of the plans was conducted in terms of dose volume histogram analysis of the target volume and organs at risk (OARs) along with total plan monitor units and beam-on time. Paired sample t test was performed to compare Dmax and Dmean of OARs for each plan's comparison. The delivery of volumetric modulated arc therapy plans was evaluated using Octavius 4D phantom. Results: All plans demonstrated dose distributions with sufficient planned target volume conformity and homogeneity. The Homogeneity Index and Conformity Index for all plans were found comparable. The paired sample t test did not demonstrate significant difference in terms of Dmax and Dmean of OARs between plans for both patients. All plans met the threshold of 90%, with Halcyon plans having higher gamma passing rates. Conclusions: Craniospinal irradiation plans generated for Halcyon and Edge are equivalent in terms of plan quality and dose sparing at OARs. The small variations may have originated from the differences in beam profile or mean energy, the degree of the modulation for each plan and characteristics of multi leaf collimators for each treatment unit. Halcyon is able to deliver a distinctly faster treatment, but Edge provides an automatic rotational correction for patient positioning.

Changing the Microstructural and Chemical Properties of Graphene Oxide Through a Chemical Route.

The aim of this work is to investigate the possibility of engineering desired molecular sp2 structures in graphene oxide, via controlled oxidation of graphite powder, in order to achieve tunable chemical and microstructural properties useful for optoelectronics or sensing applications. Specifically, GO powder is obtained by a modified Hummers method, by using different concentrations of potassium permanganate (KMnO4) in order to change the number of oxygen functionalities in the graphitic structure. Then, a successive alkaline treatment is performed by increasing the KOH concentration. The alkaline treatment induces a noticeable variation of the GO microstructural and chemical properties, which is accompanied by a strong enhancement of photoluminecence. PL and PLE measurements reveal that the configuration of electronic energy states changes as a function of the KMnO4 and KOH concentration, by introducing further electronic n levels available for n→π* transitions. In particular, the number of sp2 small domains embedded among oxygen-sp3 domains, increases under the KOH treatment, due to the addition of OH groups. Most of these sp2 domains are lifted-off from GO and thrown away in the surnatant giving it high blue photoluminescence excited at λexc ∼ 319 nm. The employ of combined spectroscopy techniques allows a deep investigation of the microstructural and chemical changes induced by chemical treatments, opening the way to the fine tuning of GO functional properties.

Synchronous bilateral chest wall irradiation with regional nodal irradiation: A literature review of techniques and a case study.

The optimal radiotherapy technique for patients requiring both breasts or chest walls simultaneous irradiation with or without regional nodal irradiation is currently under investigation. In the last decade several publications present case reports and case series of patients treated with adjuvant radiotherapy in both breasts or chest walls for synchronous bilateral breast cancer (SBBC) with modern radiotherapy techniques. This article presents a systematic review of relevant literature as well as a case report of a SBBC patient who received bilateral chest wall radiotherapy with regional nodal irradiation at our institution with Truebeam - Edge Linear Accelerator. Solid evidence is provided that the practice of avoiding adjuvant radiotherapy in SBBC out of fear of toxicity with older radiotherapy techniques is outdated. Modern techniques can safely and effectively deliver treatment to patients requiring both sides irradiation and even in mastectomy patients in need of regional nodal irradiation.

Implications of extreme serum neurofilament light chain levels for the management of patients with relapsing multiple sclerosis.

BACKGROUND: Serum neurofilament light chain (sNfL) is a promising biomarker to complement the decision-making process in multiple sclerosis (MS) patients. However, although sNfL levels are able to detect disease activity and to predict future disability, the growing evidence has not yet been translated into practicable recommendations for an implementation into clinical routine. METHODS: The observation of a patient with extensive inflammatory activity in magnetic resonance imaging (MRI) along with an extremely high sNfL level in the absence of any clinical symptoms prompted us to investigate common characteristics of our MS patients with the highest sNfL levels in a retrospective cohort study. The 97.5th percentile was chosen as a cut-off value because the mean sNfL level of the resulting extreme neurofilament light chain (NfL) cohort corresponded well to the sNfL level of the presented case. Patient characterization included clinical and MRI assessment with a focus on disease activity markers. sNfL levels were determined by single molecule array. RESULTS: The 97.5th percentile of our MS cohort (958 sNfL measurements in 455 patients) corresponded to a threshold value of 46.1 pg/ml. The mean sNfL level of the extreme sNfL cohort (n = 24) was 95.6 pg/ml (standard deviation 68.4). Interestingly, only 15 patients suffered from a relapse at the time point of sample collection, whereas nine patients showed no signs of clinical disease activity. sNfL levels of patients with and without relapse did not differ [median 81.3 pg/ml (interquartile range [IQR] 48.0-128) versus 80.2 pg/ml (IQR 46.4-97.6), p = 0.815]. The proportion of patients with contrast-enhancing lesions was high and also did not differ between patients with and without relapse (92.9% versus 87.5%, p = 0.538); 78.9% of the patients not receiving a high-efficacious therapy had ongoing disease activity during a 2-year follow-up. CONCLUSION: Extremely high sNfL levels are indicative of subclinical disease activity and might complement treatment decisions in ambiguous cases.

The need for a dose constraint in hip prosthesis to minimize later hip dysfunction. A retrospective analysis of relevant cases.

Results from a single-institution study support the need of a dose constraint for patients who have previously undergone hip replacement surgery. Our study provides evidence that a dose above 30 Gy to the area of hip prosthesis is significantly correlated with later hip arthroplasty dysfunction as measured by the Harris Hip Score. As total hip arthroplasty becomes more and more common, it is urgent to further look into radiation therapy treatment parameters that can be modified to improve the quality of life of patients who receive pelvic irradiation after hip arthroplasty. Further prospective studies are needed to extract safe conclusions.

Two hypofractionated schedules for early stage breast cancer: Comparative retrospective analysis for acute and late radiation induced dermatitis.

PURPOSE: To compare two hypofractionated radiation schedules in early breast cancer concerning skin toxicity. METHODS: We retrospectively analyzed 80 patients (group A) versus 54 (group B) who underwent hypofractionated radiotherapy after breast conserving surgery. Group Α received 42.75Gy in 15 fractions over 5 weeks (3 fractions/ week) plus 8.55Gy boost to the tumor bed (3 fractions). Group Β received 45.05Gy (5 fractions/week) and 7.95Gy boost (3 fractions). Multivariate logistic regression analysis (MVLRA) was conducted for relevant parameters regarding RTOG/EORTC skin toxicity. RESULTS: Median follow up was 60 months. Median age was 75 years (group A) and 56 (group B). Mean values of radio-dermatitis were significantly higher in group A vs B until 3 months post RT (p<0.001 and p=0.002, respectively), while 6 months thereafter toxicity was regressed without any significant difference between groups. MVLRA showed a significant (p<0.001) odds ratio for age (2.36, 95%CI:1.11-3.75) and group A (1.31, 95%CI:1.12-1.49). CONCLUSION: Schedule B would be preferable in younger women in favor of toxicity. Schedule A could still be applied in elderly patients, unavailable attending daily schedules, with acceptable toxicity.

Hepatocellular Carcinoma: An Uncommon Metastasis in the Orbit.

Hepatocellular carcinoma (HCC) represents the most common type of primary cancer of the liver and is associated with poor prognosis. It is the most common cause of death in cirrhotic patients and in different studies was shown as the third most common cause of cancer-related deaths worldwide. Each year, approximately half a million people are diagnosed with HCC. In recent decades, the prognosis of patients with HCC has improved because more cases are diagnosed and treated at early stages; high-risk patients (i.e., with chronic HBV or HCV infection) are followed more often for the possibility of HCC, and novel treatment options such as locoregional therapy are used with better overall results. The extrahepatic metastases represent a poor prognostic factor. The most common sites of metastasis in advanced hepatocellular carcinoma are the lung (44%), portal vein (35%), and portal lymph nodes (27%). Also, intra-abdominal lymph nodes and bones are common sites. Orbital metastases rarely occur, representing the 3-7% of orbital masses. These metastases are usually found in advanced tumor stages. The mechanism of metastasis to the orbit is difficult to determine. A hematogenous route, as for other primary neoplasms of the abdomen, may be suspected. Tumor cells may circulate through the vena cava, beyond the pulmonary filter to the heart, and finally be distributed to the orbital region through the arterial systemic circulation. We describe herein a case of an adult male with liver cirrhosis due to alcohol abuse who presented with concomitant diagnosis of HCC and orbit metastasis.

Evaluation of Antifouling Potential and Ecotoxicity of Secondary Metabolites Derived from Red Algae of the Genus Laurencia.

Red algae of the genus Laurencia are known to biosynthesize and secrete an immense variety of secondary metabolites possessing a spectrum of biological activities against bacteria, invertebrates and mammalian cell lines. Following a rigorous cross-species screening process, herein we report the antifouling potential of 25 secondary metabolites derived from species of the genus Laurencia, as well as the thorough evaluation of the ecotoxicity of selected metabolites against non-target marine arthropods and vertebrate cell lines. A number of these secondary metabolites exhibited potent antifouling activity and performed well in all screening tests. Our results show that perforenol (9) possesses similar antifouling activity with that already described for bromosphaerol, which is used herein as a benchmark.

From Whole-Brain Radiotherapy to Immunotherapy: A Multidisciplinary Approach for Patients with Brain Metastases from NSCLC.

Non-small cell lung cancer patients with brain metastases have a multitude of treatment options, but there is currently no international and multidisciplinary consensus concerning their optimal treatment. Local therapies have the principal role, especially in symptomatic patients. Advances in surgery and radiation therapy manage considerable local control. Systemic treatments have shown effect in clinical trials and in real life clinical settings; yet, at present, this is restricted to patients with asymptomatic or stable intracranial lesions. Targeted agents can have a benefit only in patients with EGFR mutations or ALK rearrangement. Immunotherapy has shown impressive results in patients with PD-L1 expression in tumor cells. Its effects can be further enhanced by a synergy with radiotherapy, possibly by increasing the percentage of responders. The present review summarizes the need for more effective systemic treatments, so that the increased intracranial control achieved by local treatments can be translated in an increase in overall survival.

Should I stay or should I go? The settlement-inducing protein complex guides barnacle settlement decisions.

Reproduction in barnacles relies on chemical cues that guide their gregarious settlement. These cues have been pinned down to several sources of settlement pheromones, one of which is a protein termed settlement-inducing protein complex (SIPC), a large glycoprotein acting as a pheromone to induce larval settlement and as an adhesive in surface exploration by the cyprids. Settlement assays in laboratory conditions with Amphibalanus (=Balanus) amphitrite cyprids in the presence of SIPC showed that cyprids exhibit settlement preference behaviour at lower concentrations of SIPC [half maximal effective concentration (EC50)=3.73 nmol l-1] and settlement avoidance behaviour at higher concentrations (EC50=101 nmol l-1). By using truncated fragments of SIPC in settlement assays, we identify that domains at the N-terminus of SIPC transduce settlement preference cues that mask the settlement avoidance cues transduced by domains at its C-terminus. Removing the N-terminal 600 amino acids from SIPC resulted in truncated fragments that transduced only settlement avoidance cues to the cyprids. From the sexual reproduction point of view, this bimodal response of barnacles to SIPC suggests that barnacles will settle gregariously when conspecific cues are sparse but will not settle if conspecific cues inform of overcrowding that will increase reproductive competition and diminish their reproductive chances.