Pulsed Electric Field Ablation versus Radiofrequency Thermal Ablation in Murine Breast Cancer Models: Anticancer Immune Stimulation, Tumor Response, and Abscopal Effects.

PURPOSE: To compare the immune response and survival after size-matched radiofrequency (RF) ablation and a proprietary form of pulsed electric field (PEF) ablation in murine tumors. MATERIAL AND METHODS: Orthotopically inoculated EMT6 or 4T1 murine tumors received sham, RF ablation, or PEF ablation. 4T1 tumor ablations included subgroups with intraperitoneal checkpoint inhibition immunotherapy (αPD-1). Blood was collected for cytokine profiling and flow cytometry. Tumor size was measured and survival was monitored. Tumor samples were processed for histology, immunohistochemistry, flow cytometry, and cytokine profiling. Lungs were collected from 4T1-bearing mice for hematoxylin and eosin histology to assess metastatic spread and abscopal effect induced by ablation. RESULTS: PEF elicited distinct immunomodulatory effects, with clear differences in serum and tumor cytokine profiles compared with RF ablation, including intratumoral downregulation of vascular endothelial growth factor, hypoxia-inducible factor 1α, c-MET, interleukin-10, Ki67, and tumor necrosis factor-α (all P < .05). PEF increased innate immune activation, with enhanced recruitment of dendritic cells, M1 macrophages, and natural killer cells coupled with a reduction in M2 macrophages and myeloid-derived suppressor cells (all P < .05). Concurrently, PEF strengthened adaptive immunity compared with RF ablation, characterized by increased antigen-specific T cells and decreased regulatory T cells (all P < .05). PEF stalled tumor growth and increased survival at the end of the study (≥4× versus RFA). Finally, PEF promoted an abscopal effect of clearing metastases in the lungs, which was stronger in combination with αPD-1 than with PEF alone. CONCLUSIONS: The proprietary form of PEF used in this study evoked a preferential immunostimulatory profile versus RF ablation thermal ablation in mice, with implications for enhancing the therapeutic effectiveness of checkpoint inhibition immunotherapy for immunotherapy-unresponsive tumors.

Characteristics of pulsed electric field cardiac ablation porcine treatment zones with a focal catheter.

OBJECTIVES: Pulsed electric field (PEF) therapies employ punctuated energy delivery to kill cells in a volume of tissue through mechanisms that are not dependent on thermal processes. A key component to successful cardiac ablation procedures is ensuring the generation of transmural, contiguous ablation zones, which requires in-depth knowledge regarding treatment sizes for a given therapeutic application. METHODS: In this study, a series of acute treatments were delivered to porcine ventricles, where triphenyl tetrazolium chloride (TTC) vitality stain was used to identify treatment effect sizes for the three focal monopolar CENTAURI PEF cardiac ablation energy settings. RESULTS: Treatment depths were 5.7, 7.2, and 8.2 mm for the 19, 22, and 25 A energy settings, respectively. Gross pathology indicated umbral zones of hemorrhage surrounded by pale avital TTC-negative-negative tissue, which contrasted significantly from radiofrequency ablation (RF) controls. Histologically, treatment zones are identified by regions of contraction band necrosis and cardiomyocytolysis, which contrasted with RF control lesions composed primarily of coagulation necrosis. CONCLUSIONS: Together, these data indicate the ability for focal monopolar PEF treatments to generate deep treatment zones in cardiac ablation without incurring the gross or histological coagulative characteristics of RF thermal lesions.

Large-Area Periodic Arrays of Atomically Flat Single-Crystal Gold Nanotriangles Formed Directly on Substrate Surfaces.

The advancement of nanoenabled wafer-based devices requires the establishment of core competencies related to the deterministic positioning of nanometric building blocks over large areas. Within this realm, plasmonic single-crystal gold nanotriangles represent one of the most attractive nanoscale components but where the formation of addressable arrays at scale has heretofore proven impracticable. Herein, a benchtop process is presented for the formation of large-area periodic arrays of gold nanotriangles. The devised growth pathway sees the formation of an array of defect-laden seeds using lithographic and vapor-phase assembly processes followed by their placement in a growth solution promoting planar growth and threefold symmetric side-faceting. The nanotriangles formed in this high-yield synthesis distinguish themselves in that they are epitaxially aligned with the underlying substrate, grown to thicknesses that are not readily obtainable in colloidal syntheses, and present atomically flat pristine surfaces exhibiting gold atoms with a close-packed structure. As such, they express crisp and unambiguous plasmonic modes and form photoactive surfaces with highly tunable and readily modeled plasmon resonances. The devised methods, hence, advance the integration of single-crystal gold nanotriangles into device platforms and provide an overall fabrication strategy that is adaptable to other nanomaterials.

International consensus statement: methods for recording and reporting of epidemiological data on injuries and illnesses in golf.

Epidemiological studies of injury in elite and recreational golfers have lacked consistency in methods and definitions employed and this limits comparison of results across studies. In their sports-generic statement, the Consensus Group recruited by the IOC (2020) called for sport-specific consensus statements. On invitation by International Golf Federation, a group of international experts in sport and exercise medicine, golf research and sports injury/illness epidemiology was selected to prepare a golf-specific consensus statement. Methodological stages included literature review and initial drafting, online feedback from the consensus group, revision and second draft, virtual consensus meetings and completion of final version. This consensus statement provides golf-specific recommendations for data collection and research reporting including: (i) injury and illness definitions, and characteristics with golf-specific examples, (ii) definitions of golf-specific exposure measurements and recommendations for the calculation of prevalence and incidence, (iii) injury, illness and exposure report forms for medical staff and for golfers, and (iv) a baseline questionnaire. Implementation of the consensus methodology will enable comparison among golf studies and with other sports. It facilitates analysis of causative factors for injuries and illness in golf, and can also be used to evaluate the effects of prevention programmes to support the health of golfers.

Plasmon-Mediated Synthesis of Periodic Arrays of Gold Nanoplates Using Substrate-Immobilized Seeds Lined with Planar Defects.

The seed-mediated growth of noble metal nanostructures with planar geometries requires the use of seeds lined with parallel stacking faults so as to provide a break in symmetry in an otherwise isotropic metal. Although such seeds are now routinely synthesized using colloidal pathways, equivalent pathways have not yet been reported for the fabrication of substrate-based seeds with the same internal defect structures. The challenge is not merely to form seeds with planar defects but to do so in a deterministic manner so as to have stacking faults that only run parallel to the substrate surface while still allowing for the lithographic processes needed to regulate the placement of seeds. Here, we demonstrate substrate-imposed epitaxy as a viable synthetic control able to induce planar defects in Au seeds while simultaneously dictating nanostructure in-plane alignment and crystallographic orientation. The seeds, which are formed in periodic arrays using nanoimprint lithography in combination with a vapor-phase assembly process, are subjected to a liquid-phase plasmon-mediated synthesis that uses light as an external stimuli to drive a reaction yielding periodic arrays of hexagonal Au nanoplates. These achievements not only represent the first of their kind demonstrations but also advance the possibility of integrating wafer-based technologies with a rich and exciting nanoplate colloidal chemistry.

Effects of internal electrode cooling on irreversible electroporation using a perfused organ model.

PURPOSE: This study evaluates the effects of active electrode cooling, via internal fluid circulation, on the irreversible electroporation (IRE) lesion, deployed electric current and temperature changes using a perfused porcine liver model. MATERIALS AND METHODS: A bipolar electrode delivered IRE electric pulses with or without activation of internal cooling to nine porcine mechanically perfused livers. Pulse schemes included a constant voltage, and a preconditioned delivery combined with an arc-mitigation algorithm. After treatment, organs were dissected, and treatment zones were stained using triphenyl-tetrazolium chloride (TTC) to demonstrate viability. RESULTS: Thirty-nine treatments were performed with an internally cooled applicator and 21 with a non-cooled applicator. For the constant voltage scenario, the average final electrical current measured was 26.37 and 29.20 A for the cooled and uncooled electrodes respectively ([Formula: see text]). The average final temperature measured was 33.01 and 42.43 °C for the cooled and uncooled electrodes respectively ([Formula: see text]). The average measured ablations (fixed lesion) were 3.88-by-2.08 cm and 3.86-by-2.12 cm for the cooled and uncooled electrode respectively ([Formula: see text], [Formula: see text]). Similarly, the preconditioned/arc-mitigation scenario yielded an average final electrical current measurement of a 41.07 and 47.20 A for the cooled and uncooled electrodes respectively ([Formula: see text]). The average final temperature measured was 34.93 and 44.90 °C for the cooled and uncooled electrodes respectively ([Formula: see text]). The average measured ablations (fixed lesion) were 3.67-by-2.27 cm and 3.58-by-2.09 cm for the cooled and uncooled applicators ([Formula: see text]). CONCLUSIONS: The internally-cooled bipolar applicator offers advantages that could improve clinical outcomes. Thermally mitigating internal perfusion technology reduced tissue temperatures and electric current while maintaining similar lesion sizes.

Characterization of Irreversible Electroporation Ablation with a Validated Perfused Organ Model.

PURPOSE: To develop and validate a perfused organ model for characterizing ablations for irreversible electroporation (IRE)-based therapies. MATERIALS AND METHODS: Eight excised porcine livers were mechanically perfused with a modified phosphate-buffered saline solution to maintain viability during IRE ablation. IRE pulses were delivered using 2 monopolar electrodes over a range of parameters, including voltage (1,875-3,000 V), pulse length (70-100 µsec), number of pulses (50-600), electrode exposure (1.0-2.0 cm), and electrode spacing (1.5-2.0 cm). Organs were dissected, and treatment zones were stained with triphenyl tetrazolium chloride to demonstrate viability and highlight the area of ablation. Results were compared with 17 in vivo ablations performed in canine livers and 35 previously published ablations performed in porcine livers. RESULTS: Ablation dimensions in the perfused model correlated well with corresponding in vivo ablations (R2 = 0.9098) with a 95% confidence interval of < 2.2 mm. Additionally, the validated perfused model showed that the IRE ablation zone grew logarithmically with increasing pulse numbers, showing small difference in ablation size over 200-600 pulses (3.2 mm ± 3.8 width and 5.2 mm ± 3.9 height). CONCLUSIONS: The perfused organ model provides an alternative to animal trials for investigation of IRE treatments. It may have an important role in the future development of new devices, algorithms, and techniques for this therapy.

Optimizing Irreversible Electroporation Ablation with a Bipolar Electrode.

PURPOSE: To optimize single-insertion bipolar irreversible electroporation (IRE) by characterizing effects of electric parameters and controlling tissue electric properties in a porcine model. MATERIALS AND METHODS: Single-insertion electrode bipolar IRE was performed in 28 in vivo pig livers (78 ablations). First, effects of voltage (2,700-3,000 V), number of pulses, repeated cycles (1-6 cycles), and pulse width (70-100 µs) were studied. Next, electric conductivity was altered by instillation of hypertonic and hypotonic fluids. Finally, effects of thermal stabilization were assessed using internal electrode cooling. Treatment effect was evaluated 2-3 hours after IRE. Dimensions were compared and subjected to statistical analysis. RESULTS: Delivering 3,000 V at 70 µs for a single 90-pulse cycle yielded 3.8 cm ± 0.4 × 2.0 cm ± 0.3 of ablation. Applying 6 cycles of energy increased ablation to 4.5 cm ± 0.4 × 2.6 cm ± 0.3 (P < .001). Further increasing pulse lengths to 100 µs (6 cycles) increased ablation to 5.0 cm ± 0.4 × 2.9 cm ± 0.3 (P < .001) but resulted in electric spikes and system crashes in 40%-50% of cases. Increasing tissue electric conductivity via hypertonic solution instillation in surrounding tissues increased frequency of generator crashes, whereas continuous instillation of distilled water eliminated this arcing phenomenon but reduced ablation to 2.3 cm ± 0.1. Controlled instillation of distilled water when electric arcing was suspected from audible popping produced ablations of 5.3 cm ± 0.6 × 3.1 cm ±0.3 without crashes. Finally, 3.1 cm ± 0.1 short-axis ablation was achieved without system crashes with internal electrode perfusion at 37°C versus 2.3 cm ± 0.1 with 4°C-10°C perfusion (P < .001). CONCLUSIONS: Bipolar IRE ablation zones can be increased with repetitive high voltage and greater pulse widths accompanied by either judicious instillation of hypotonic fluids or internal electrode perfusion to minimize unwanted electric arcing.

Narcotic Use: A Modifiable Risk Factor for Hip and Knee Arthroplasty.

The use of opioids in the United States has become an epidemic. Opioids have become frequently prescribed for arthritic pain in the hip and knee. The use of opioidsas first-round therapy for pain has been driven by several factors, including the health care providers' lack of understanding that anti-inflammatory medications are at least as effective as opioids, a patient's expectation of complete pain relief on presentation to the emergency room or doctor's office, and increasing importance placed on patient satisfaction. The harmful effects of opioids are observed after joint replacement with long-term use leading to worse results after joint replacement. Decreasing the amount of opioids used before surgery improves outcomes after surgery. The use of opioids may be modified before surgery to give better surgical results. The goal of this review is to determine how opioid medications should fit into the treatment of arthritis pain, learn the guidelines for their use in arthritis, and understand how to educate health care providers that opioid use is a modifiable risk factor.

Implications and considerations of thermal effects when applying irreversible electroporation tissue ablation therapy.

Irreversible electroporation (IRE) describes a cellular response to electric field exposure, resulting in the formation of nanoscale defects that can lead to cell death. While this behavior occurs independently of thermally-induced processes, therapeutic ablation of targeted tissues with IRE uses a series of brief electric pulses, whose parameters result in secondary Joule heating of the tissue. Where contemporary clinical pulse protocols use aggressive energy regimes, additional evidence is supplementing original studies that assert care must be taken in clinical ablation protocols to ensure the cumulative thermal effects do not induce damage that will alter outcomes for therapies using the IRE non-thermal cell death process for tissue ablation. In this letter, we seek to clarify the nomenclature regarding IRE as a non-thermal ablation technique, as well as identify existing literature that uses experimental, clinical, and numerical results to discretely address and evaluate the thermal considerations relevant when applying IRE in clinical scenarios, including several approaches for reducing these effects. Existing evidence in the literature describes cell response to electric fields, suggesting cell death from IRE is a unique process, independent from traditional thermal damage. Numerical simulations, as well as preclinical and clinical findings demonstrate the ability to deliver therapeutic IRE ablation without occurrence of morbidity associated with thermal therapies. Clinical IRE therapy generates thermal effects, which may moderate the non-thermal aspects of IRE ablation. Appropriate protocol development, utilization, and pulse delivery devices may be implemented to restrain these effects and maintain IRE as the vastly predominant tissue death modality, reducing therapy-mitigating thermal damage. Clinical applications of IRE should consider thermal effects and employ protocols to ensure safe and effective therapy delivery.

In vivo characterization and numerical simulation of prostate properties for non-thermal irreversible electroporation ablation.

BACKGROUND: Irreversible electroporation (IRE) delivers brief electric pulses to attain non-thermal focal ablation that spares vasculature and other sensitive systems. It is a promising prostate cancer treatment due to sparing of the tissues associated with morbidity risk from conventional therapies. IRE effects depend on electric field strength and tissue properties. These characteristics are organ-dependent, affecting IRE treatment outcomes. This study characterizes the relevant properties to improve treatment planning and outcome predictions for IRE prostate cancer treatment. METHODS: Clinically relevant IRE pulse protocols were delivered to a healthy canine and two human cancerous prostates while measuring electrical parameters to determine tissue characteristics for predictive treatment simulations. Prostates were resected 5 hr, 3 weeks, and 4 weeks post-IRE. Lesions were correlated with numerical simulations to determine an effective prostate lethal IRE electric field threshold. RESULTS: Lesions were produced in all subjects. Tissue electrical conductivity increased from 0.284 to 0.927 S/m due to IRE pulses. Numerical simulations show an average effective prostate electric field threshold of 1072 ± 119 V/cm, significantly higher than previously characterized tissues. Histological findings in the human cases show instances of complete tissue necrosis centrally with variable tissue effects beyond the margin. CONCLUSIONS: Preliminary experimental IRE trials safely ablated healthy canine and cancerous human prostates, as examined in the short- and medium-term. IRE-relevant prostate properties are now experimentally and numerically defined. Importantly, the electric field required to kill healthy prostate tissue is substantially higher than previously characterized tissues. These findings can be applied to optimize IRE prostate cancer treatment protocols.

Absence of Arrhythmogenicity with Biphasic Pulsed Electric Fields Delivered to Porcine Airways.

Pulsed electric field (PEF) technologies treat many types of tissue. Many systems mandate synchronization to the cardiac cycle to avoid the induction of cardiac arrhythmias. Significant differences between PEF systems make the assessment of cardiac safety from one technology to another challenging. A growing body of evidence suggests that shorter duration biphasic pulses obviate the need for cardiac synchronization, even when delivered in a monopolar fashion. This study theoretically evaluates the risk profile of different PEF parameters. It then tests a monopolar, biphasic, microsecond-scale PEF technology for arrhythmogenic potential. PEF applications of increasing likelihood to induce an arrhythmia were delivered. The energy was delivered throughout the cardiac cycle, including both single and multiple packets, and then with concentrated delivery on the t-wave. There were no sustained changes to the electrocardiogram waveform or to the cardiac rhythm, despite delivering energy during the most vulnerable phase of the cardiac cycle, and delivery of multiple packets of PEF energy across the cardiac cycle. Only isolated premature-atrial contractions (PAC) were observed. This study provides evidence that certain varieties of biphasic, monopolar PEF delivery do not require synchronized energy delivery to prevent harmful arrhythmias.

Neoadjuvant chemo-immunotherapy is improved with a novel pulsed electric field technology in an immune-cold murine model.

Chemo-immunotherapy uses combined systemic therapies for resectable and unresectable tumors. This approach is gaining clinical momentum, but survival increases leave considerable room for improvement. A novel form of Pulsed Electric Field (PEF) ablation combines focal tissue destruction with immune activation in preclinical settings. The PEFs induce lethal cell damage without requiring thermal processes, leaving cellular proteins intact. This affords PEF a favorable safety profile, improved antigenicity, and significant immunostimulatory damage-associated molecular pattern release compared to other focal therapies. Preclinical investigations demonstrate a combinatorial benefit of PEF with immunostimulation. This study evaluates whether this proprietary PEF therapy induces an immunostimulatory effect sufficient to augment systemic neoadjuvant chemotherapy and immunotherapy to reverse metastatic disease in an immune-cold murine tumor model. To determine whether PEF improves a neoadjuvant chemo-immunotherapy standard-of-care, partial PEF ablation was delivered to orthotopically inoculated 4T1 metastatic tumors in addition to combinations of cisplatin chemotherapy and/or αPD-1 immunotherapy, followed by resection. In addition, to determine whether PEF combined with chemo-immunotherapy improves local and metastatic response in unresectable populations, partial PEF ablation was added to chemo-immunotherapy in mice that did not receive resection. Blood cytokines and flow cytometry evaluated immune response. Partial PEF ablation generates an immunostimulatory tumor microenvironment, increases systemic immune cell populations, slows tumor growth, and prolongs survival relative to neoadjuvant systemic therapies-alone. These data suggest the addition of this proprietary PEF locoregional therapy may synergize with systemic standard-of-care paradigms to improve outcomes with potential or demonstrated metastatic disease in both resectable and unresectable patient cohorts.

Effects of Contact Force on Lesion Size During Pulsed Field Catheter Ablation: Histochemical Characterization of Ventricular Lesion Boundaries.

BACKGROUND: Effects of contact force (CF) on lesion formation during pulsed field ablation (PFA) have not been well validated. The purpose of this study was to determine the relationship between average CF and lesion size during PFA using a swine-beating heart model. METHODS: A 7F catheter with a 3.5-mm ablation electrode and CF sensor (TactiCath SE, Abbott) was connected to a PFA system (CENTAURI, Galvanize Therapeutics). In 5 closed-chest swine, biphasic PFA current was delivered between the ablation electrode and a skin patch at 40 separate sites in right ventricle (28 Amp) and 55 separate sites in left ventricle (35 Amp) with 4 different levels of CF: (1) low (CF range of 4-13 g; median, 9.5 g); (2) moderate (15-30 g; median, 21.5 g); (3) high (34-55 g; median, 40 g); and (4) no electrode contact, 2 mm away from the endocardium. Swine were sacrificed at 2 hours after ablation, and lesion size was measured using triphenyl tetrazolium chloride staining. In 1 additional swine, COX (cytochrome c oxidase) staining was performed to examine mitochondrial activity to delineate reversible and irreversible lesion boundaries. Histological examination was performed with hematoxylin and eosin and Masson trichrome staining. RESULTS: Ablation lesions were well demarcated with triphenyl tetrazolium chloride staining, showing (1) a dark central zone (contraction band necrosis and hemorrhage); (2) a pale zone (no mitochondrial activity and nuclear pyknosis, indicating apoptosis zone); and a hyperstained zone by triphenyl tetrazolium chloride and COX staining (unaffected normal myocardium with preserved mitochondrial activity, consistent with reversible zone). At constant PFA current intensity, lesion depth increased significantly with increasing CF. There were no detectable lesions resulting from ablation without electrode contact. CONCLUSIONS: Acute PFA ventricular lesions show irreversible and reversible lesion boundaries by triphenyl tetrazolium chloride staining. Electrode-tissue contact is required for effective lesion formation during PFA. At the same PFA dose, lesion depth increases significantly with increasing CF.

30-year-old woman • progressive dyspnea and peripheral edema • 35th week of gestation with a history of mild preeclampsia • Dx?

► progressive dyspnea and peripheral edema ► 35th week of gestation with a history of mild preeclampsia.

Thermal Profiles for Focal Pulsed Electric Field Ablation.

BACKGROUND: Pulsed electrical field (PEF) ablation may cause tissue heating. These changes are reportedly small, but each PEF system and waveform will have a different behavior, and data are lacking. OBJECTIVES: This study sought to compare the temperature profile of focal point, monopolar biphasic PEF ablation versus radiofrequency (RF). METHODS: Ablation lesions were performed on perfused thigh muscle of swine. PEF lesions were performed with 3 compatible ablation catheters at the highest (25 amp) energy, and 1 catheter (Tacticath SE) was also used at the 22- and 19-amp levels. Temperature changes in the tissue were measured using fluoroptic temperature probes inserted at the muscle surface, as well as 3 mm and 7 mm below the surface. Temperatures were recorded continuously at baseline, during delivery, and after ablation. Muscle temperatures were compared with those of RF lesions performed with 1 catheter (Tacticath SE) at 30 W for 30 seconds. RESULTS: PEF ablation with 3energy settings produced small temperature changes. Maximum average temperature rise for PEF for the maximum (25-amp) energy setting (32 lesions) was 7.6 °C, 2.8 °C, and 0.9 °C at the surface, 3-mm depth, and 7-mm depth, respectively. The temperature rise was dose dependent, with lower energy settings yielding less temperature rise. RF ablations (10 lesions) produced temperature increases of 16.6 °C, 39.8 °C, and 9.5 °C at the surface, 3-mm depth, and 7-mm depth, respectively. CONCLUSIONS: PEF caused detectable temperature changes in muscle tissue, which never exceeded 2.8 °C at the 3-mm depth versus baseline. By contrast, RF produced substantial temperature rises. These data support that focal monopolar biphasic energy delivered by this PEF technology retains a favorable thermal safety profile.

Periodic arrays of structurally complex oxide nanoshells and their use as substrate-confined nanoreactors.

Sacrificial templates present an effective pathway for gaining high-level control over nanoscale reaction products. Atomic layer deposition (ALD) is ideally suited for such approaches due to its ability to replicate the surface topography of a template material through the deposition of an ultrathin conformal layer. Herein, metal nanostructures are demonstrated as sacrificial templates for the formation of architecturally complex and deterministically positioned oxide nanoshells, open-topped nanobowls, vertically standing half-shells, and nanorings. The three-step process sees metal nanocrystals formed in periodic arrays, coated with an ALD-deposited oxide, and hollowed out with a selective etch through nanopores formed in the oxide shell. The procedure is further augmented through the use of a directional ion beam that is used to sculpt the oxide shells into bowl- and ring-like configurations. The functionality of the so-formed materials is demonstrated through their use as substrate-confined nanoreactors able to promote the growth and confinement of nanomaterials. Taken together, the work expands the design space for substrate-based nanomaterials, creates a platform for advancing functional surfaces and devices and, from a broader perspective, advances the use of ALD in forming complex nanomaterials.

Evidence of anticipatory forest use behaviours under policy introduction: a systematic map protocol.

Background: Forest conservation is a major global policy goal, due to the role forests play in climate change mitigation and biodiversity conservation. It is well recognized that the introduction of policies, whether aimed at forest conservation or with other objectives, has the potential to trigger unintended outcomes, such as displacement or leakage, which can undermine policy objectives. However, a set of outcomes that has escaped detailed scrutiny are anticipatory forest use behaviours, emerging when forest stakeholders anticipate policy implementation, deploying for example pre-emptive forest clearing, resulting in detrimental environmental outcomes. Lack of understanding of the extent and sectorial scope of these behaviours prevents us from devising strategies to address their potential detrimental consequences. Methods: This protocol presents the methodology that will be followed to conduct a systematic map to identify, compile, review and describe the evidence available on anticipatory forest use behaviours in the context of policy introduction around the world. We will use two complementary search strategies, which we have tested before submitting this protocol. First, a systematic bibliographic search, and second, a citation chase approach. We will include articles based on a pre-defined set of criteria defined according to a Population, Intervention and Outcome (i.e. PIO) design. To support identification of knowledge gaps and clusters, we will report results of the systematic map in a narrative synthesis, an evidence atlas and other visualisations. Supplementary Information: The online version contains supplementary material available at 10.1186/s13750-023-00307-0.

An induced annual modulation signature in COSINE-100 data by DAMA/LIBRA's analysis method.

The DAMA/LIBRA collaboration has reported the observation of an annual modulation in the event rate that has been attributed to dark matter interactions over the last two decades. However, even though tremendous efforts to detect similar dark matter interactions were pursued, no definitive evidence has been observed to corroborate the DAMA/LIBRA signal. Many studies assuming various dark matter models have attempted to reconcile DAMA/LIBRA's modulation signals and null results from other experiments, however no clear conclusion can be drawn. Apart from the dark matter hypothesis, several studies have examined the possibility that the modulation is induced by variations in detector's environment or their specific analysis methods. In particular, a recent study presents a possible cause of the annual modulation from an analysis method adopted by the DAMA/LIBRA experiment in which the observed annual modulation could be reproduced by a slowly varying time-dependent background. Here, we study the COSINE-100 data using an analysis method similar to the one adopted by the DAMA/LIBRA experiment and observe a significant annual modulation, however the modulation phase is almost opposite to that of the DAMA/LIBRA data. Assuming the same background composition for COSINE-100 and DAMA/LIBRA, simulated experiments for the DAMA/LIBRA without dark matter signals also provide significant annual modulation with an amplitude similar to DAMA/LIBRA with opposite phase. Even though this observation does not directly explain the DAMA/LIBRA results directly, this interesting phenomenon motivates more profound studies of the time-dependent DAMA/LIBRA background data.