Novel opportunities for clinical pharmacy research: development of a machine learning model to identify medication related causes of delirium in different patient groups.

The advent of artificial intelligence (AI) technologies has taken the world of science by storm in 2023. The opportunities of this easy to access technology for clinical pharmacy research are yet to be fully understood. The development of a custom-made large language model (LLM) (DELSTAR) trained on a wide range of internationally recognised scientific publication databases, pharmacovigilance sites and international product characteristics to help identify and summarise medication related information on delirium, as a proof-of-concept model, identified new facilitators and barriers for robust clinical pharmacy practice research. This technology holds great promise for the development of much more comprehensive prescribing guidelines, practice support applications for clinical pharmacy, increased patient and prescribing safety and resultant implications for healthcare costs. The challenge will be to ensure its methodologically robust use and the detailed and transparent verification of its information accuracy.

Parkinson's disease: symptoms and medications at the end of life.

OBJECTIVES: People with Parkinson's disease (PwP) have a high palliative symptom burden throughout their disease course, equivalent to advanced malignancy. We aim to establish trends in symptom frequency and prescribing in the 72 hours prior to death for PwP. METHODS: Retrospective case note review of PwP who died between February 2019 and September 2020. RESULTS: 51 patients were included. 60.78% of patients (n=31) had agitation and 58.82% (n=30) had pain in the final 72 hours. Patients with cognitive impairment were 4.67 times more likely to experience agitation (p=0.035) compared with those without, with higher total midazolam doses (29.18 mg vs 11.4 mg, p=0.21). Terminal motor symptoms were recorded in three patients. 28.57% of patients received the recommended dose of rotigotine for dopaminergic therapy. CONCLUSIONS: PwP have a significant symptom burden at the end of life (EOL) with levels of terminal agitation at the higher end of those expected in the general population. There was a trend towards higher doses of sedation, rather than analgesia, in people with coexistent cognitive impairment.Terminal stiffness, despite being seldom documented in the literature, is an important although infrequent symptom.Rotigotine use at EOL remains commonplace and better understanding of its effect and dosing is required.

Pink, Dome-Shaped Papule of the Scalp in a Patient With Multiple Squamous Cell Carcinomas.

A 74-year-old man with a history of multiple squamous cell carcinomas presents with a 5-mm bright pink, dome-shaped papule with overlying vessels at the crown of the scalp. What is your diagnosis?

Parkinson's disease and palliative care: a quality of care Delphi study.

OBJECTIVES: Extending palliative care services to those with long-term neurological conditions is a current aim of UK health policy. Lack of holistic guidelines for palliative and end-of-life care, and differing models of service provision, has resulted in heterogeneity in care access and quality. There is a need for evidence-based standards of care to audit Parkinson's services and drive improvements. METHODS: A two-stage Delphi process was used to achieve consensus on statements that define quality standards in palliative care for patients with Parkinson's disease (PD). An expert panel was selected to comprise healthcare professionals, patients and carers based in the UK; this panel evaluated the statements via a Delphi survey. Quantitative and qualitative analysis of the results informed modifications between the Delphi rounds. RESULTS: A final set of 16 statements was produced, reflecting aspirational standards of palliative care in PD. These statements, split into four domains ('Structures and processes of care', 'Preparing for the end of life', ' Care in the last weeks of life' and 'Care in the last days of life') underline the importance of joint working between generalist and specialist services, individualised care and early and regular advance care planning. CONCLUSIONS: The Delphi process has established a set of standards which can be integrated within and guide services, helping to improve the quality and equality of care. Further work remains to establish the effectiveness of different models of service provision, including the implementation of keyworkers and telemedicine.

Parkinson's disease - palliative care needs assessment tool: adaptation and psychometric testing.

OBJECTIVE: Parkinson's disease is a progressive, life-limiting disease, which benefits from structured palliative care. Systematic recognition and triage of needs helps facilitate care, allows focused referral to specialist palliative care and aids sustainability of services. Existing palliative care tools for Parkinson's are patient/caregiver completed and focus on quantification rather than identification of the need. The Needs Assessment Tool: Progressive Disease in Cancer was designed for rapid identification of unmet needs in cancer. We describe adaptation and psychometric testing of the tool for Parkinson's disease (NAT:Parkinson's disease). METHODS: Set in secondary care, Parkinson's disease outpatient clinics in the UK, this study included people with Parkinson's, age >18, including all disease stages. People with atypical Parkinsonian syndromes were excluded. Adaptation was made using systematic review and focus groups. Construct validity was tested in 50 consecutive patients against established patient and caregiver measures, analysed with Kendall's Tau B. Inter-rater reliability, using video consultations, were calculated in broad range of clinicians involved in Parkinson's disease care using a weighted kappa; 0-0.2=slight, 0.21-0.40=fair, 0.41-0.60=moderate, 0.61-0.80=substantial and p<0.05 indicative of statistically significant agreement. RESULTS: Validity was substantial for two, moderate for five and fair for four constructs. Inter-rater reliability was substantial for one, moderate for three and fair for six constructs. Two constructs failing to demonstrate fair reliability did show very high percentage agreement. CONCLUSION: Findings support the suitability of the NAT:Parkinson's disease for everyday clinical use in the identification and triage of unmet palliative need for people with Parkinson's disease.

Adenoid ameloblastoma harbors beta-catenin mutations.

Adenoid ameloblastoma is a very rare benign epithelial odontogenic tumor characterized microscopically by epithelium resembling conventional ameloblastoma, with additional duct-like structures, epithelial whorls, and cribriform architecture. Dentinoid deposits, clusters of clear cells, and ghost-cell keratinization may also be present. These tumors do not harbor BRAF or KRAS mutations and their molecular basis appears distinct from conventional ameloblastoma but remains unknown. We assessed CTNNB1 (beta-catenin) exon 3 mutations in a cohort of 11 samples of adenoid ameloblastomas from 9 patients. Two of the 9 patients were female and 7 male and in 7/9 patients the tumors occurred in the maxilla. Tumors of 4 of these 9 patients harbored CTNNB1 mutations, specifically p.Ser33Cys, p.Gly34Arg, and p.Ser37Phe. Notably, for one patient 3 samples were analyzed including the primary tumour and two consecutive recurrences, and results were positive for the mutation in all three tumors. Therefore, 6/11 samples tested positive for the mutation. In the 6 mutation-positive samples, ghost cells were present in only 2/6, indicating beta-catenin mutations are not always revealed by ghost cell formation. Dentinoid matrix deposition was observed in 5/6 mutation-positive samples and clear cells in all 6 cases. None of the cases harbored either BRAF or KRAS mutations. Beta-catenin immunoexpression was assessed in the samples of 8 patients. Except for one wild-type case, all cases showed focal nuclear expression irrespective of the mutational status. Together with the absence of BRAF mutation, the detection of beta-catenin mutation in adenoid ameloblastomas supports its classification as a separate entity, and not as a subtype of ameloblastoma. The presence of this mutation may help in the diagnosis of challenging cases.

A Rare Presentation of Sick Sinus Syndrome: Generalized Seizures.

Cardiac and neurological disorders are the main broad etiologies for loss of consciousness. Ictal bradycardia syndrome refers to epileptic discharges that profoundly disrupt normal cardiac rhythm, resulting in cardiogenic syncope during the ictal event. Convulsive syncope is a well-described phenomenon in both adults and children in which abrupt cerebral hypoperfusion leads to brief extensor stiffening and non-sustained myoclonus. Sick sinus syndrome or tachycardia bradycardia syndrome is a common cause of arrhythmias in the elderly secondary to sinus node dysfunction. We present a case of a 91-year-old male who presented with generalized seizure with associated bradyarrhythmias with telemetry showing sinus rhythm, followed by severe bradycardia, followed by Ventricular tachycardia, followed by an episode of asystole, which likely precipitated seizures as a result of cerebral hypoperfusion. The patient had a permanent dual-chamber pacemaker. He was discharged on antiepileptics as his EEG was abnormal, which might indicate an underlying predisposition.

Tricuspid Endocarditis: A Case Report and Comprehensive Literature Review.

Infective endocarditis is a multisystem disease. Tricuspid valve endocarditis is frequently seen in patients with intravenous (IV) drug users. Cavitating lung nodules predominantly in a peripheral location in IV drug users indicate the possibility of septic emboli. Large vegetation and persistent bacteremia with septic embolic phenomena are the most common indication for surgery. We present a case of a 62-year-old male with a history of IV drug use who presented with epigastric abdominal pain, pleuritic chest pain, and shortness of breath. CT chest showed cavitating lung nodules suggestive of septic pulmonary emboli. A transesophageal echocardiogram (TEE) showed tricuspid valve vegetation despite a normal transthoracic echocardiogram. The patient was treated with intravenous antibiotics. He was deemed a poor surgical candidate; therefore, he was transferred to a tertiary center for AngioVAC (AngioDynamics, Latham, New York).

Rotigotine patch prescription in inpatients with Parkinson's disease: evaluating prescription accuracy, delirium and end-of-life use.

BACKGROUND: Rotigotine patch, a trans-dermal dopamine agonist, is used acutely to replace oral dopaminergic medications for inpatients with Parkinson's disease where enteral routes are no longer available, and is also an option in end-of-life care where patients can no longer swallow. Concerns regarding acute use of Rotigotine include difficulty achieving dopaminergic equivalence, promotion of delirium/hallucinations and promotion of terminal agitation. OBJECTIVE: our objectives were to establish: (i) accuracy of Rotigotine prescribing, (ii) rates of delirium/hallucinations and (iii) rates of terminal agitation. METHOD: we retrospectively evaluated the use of Rotigotine in an inpatient population at a UK teaching hospital. Prescriptions between January 2018 and July 2019 were identified and inpatient records were analysed. OPTIMAL Calculator 2 was used as a gold standard for assessing conversion of oral dopaminergic medication to Rotigotine. RESULTS: a total of 84 inpatients were included. 25 (30%) patients were prescribed the recommended dose of Rotigotine; 31 (37%) higher and 28 (33%) lower than recommended. A total of 15 of 41 (37%) patients with dementia and 22 of 49 (45%) patients with delirium before initiation of Rotigotine inappropriately received the higher dose; 20 (24%) patients developed new/worsening delirium and 8 (10%) patients developed new/worsening hallucinations; and 59 (70%) patients were dead at time of evaluation, of these 40 (68%) died in hospital, 10 (25%) of whom experienced terminal agitation. CONCLUSIONS: acute conversion of oral dopaminergic medication to trans-dermal Rotigotine patch remains problematic despite the availability of validated tools. Inappropriate dosing may precipitate or worsen delirium/hallucinations. Use at end-of-life requires further evaluation.

Activity- and reactivity-based proteomics: Recent technological advances and applications in drug discovery.

Activity-based protein profiling (ABPP) is recognized as a powerful and versatile chemoproteomic technology in drug discovery. Central to ABPP is the use of activity-based probes to report the activity of specific enzymes or reactivity of amino acid types in complex biological systems. Over the last two decades, ABPP has facilitated the identification of new drug targets and discovery of lead compounds in human and infectious disease. Furthermore, as part of a sustained global effort to illuminate the druggable proteome, the repertoire of target classes addressable with activity-based probes has vastly expanded in recent years. Here, we provide an overview of ABPP and summarise the major technological advances with an emphasis on probe development.

The E3/E4 ubiquitin conjugation factor UBE4B interacts with and ubiquitinates the HTLV-1 Tax oncoprotein to promote NF-κB activation.

Human T-cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia/lymphoma (ATLL), and the neurological disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The HTLV-1 Tax protein persistently activates the NF-κB pathway to enhance the proliferation and survival of HTLV-1 infected T cells. Lysine 63 (K63)-linked polyubiquitination of Tax provides an important regulatory mechanism that promotes Tax-mediated interaction with the IKK complex and activation of NF-κB; however, the host proteins regulating Tax ubiquitination are largely unknown. To identify new Tax interacting proteins that may regulate its ubiquitination we conducted a yeast two-hybrid screen using Tax as bait. This screen yielded the E3/E4 ubiquitin conjugation factor UBE4B as a novel binding partner for Tax. Here, we confirmed the interaction between Tax and UBE4B in mammalian cells by co-immunoprecipitation assays and demonstrated colocalization by proximity ligation assay and confocal microscopy. Overexpression of UBE4B specifically enhanced Tax-induced NF-κB activation, whereas knockdown of UBE4B impaired Tax-induced NF-κB activation and the induction of NF-κB target genes in T cells and ATLL cell lines. Furthermore, depletion of UBE4B with shRNA resulted in apoptotic cell death and diminished the proliferation of ATLL cell lines. Finally, overexpression of UBE4B enhanced Tax polyubiquitination, and knockdown or CRISPR/Cas9-mediated knockout of UBE4B attenuated both K48- and K63-linked polyubiquitination of Tax. Collectively, these results implicate UBE4B in HTLV-1 Tax polyubiquitination and downstream NF-κB activation.

Targeted Next-Generation Sequencing and Allele-Specific Quantitative PCR of Laser Capture Microdissected Samples Uncover Molecular Differences in Mixed Odontogenic Tumors.

The molecular pathogenesis of mixed odontogenic tumors has not been established, and understanding their genetic basis could refine their classification and help define molecular markers for diagnostic purposes. Potentially pathogenic mutations in the component tissues of 28 cases of mixed odontogenic tumors were assessed. Laser capture microdissected tissue from 10 ameloblastic fibromas (AF), 4 ameloblastic fibrodentinomas (AFD), 6 ameloblastic fibro-odontomas (AFO), 3 ameloblastic fibrosarcomas (AFS), and 5 odontomas (OD) were screened by next-generation sequencing and results confirmed by TaqMan allele-specific quantitative PCR. BRAF p.V600E mutation in the mesenchymal component was shown in 4 of 10 AF (40%), 2 of 4 AFD (50%), 2 of 6 AFO (33%), and 2 of 3 AFS (67%), whereas all 5 OD were wild type for BRAF p.V600E. Mutation in the epithelial component was only observed in one AF and one AFO. One AFS contained an area of benign AF, and the mesenchymal component of both (AFS and AF) contained BRAF p.V600E, supporting the concept of malignant progression from a benign AF precursor. KDR, TP53, KIT, and PIK3CA single-nucleotide polymorphisms are reported. In conclusion, AF, AFD, AFO, and AFS show BRAF p.V600E in their mesenchymal component, unlike OD, which are BRAF wild type, suggesting that at least a subset of AF, AFD, and AFO are molecularly distinct from OD, and may represent distinct entities and be neoplastic.

Understanding the Science Surrounding Environmental Consequences and Rehabilitation Actions Stemming from Brazil's Fundão Tailing Dam Rupture.

Collapse of the Fundão tailings dam in November 2015 in Minas Gerais, Brazil, resulted in the release of approximately 36 million cubic meters of primarily clay and fine sand-sized particles to the environment. The spill event extended over 600 km of the Rio Doce catchment and affected terrestrial and aquatic ecosystems and compromised socioeconomic activities throughout the watershed. Numerous monitoring programs and research investigations in the catchment since that time contribute to better understanding of the environmental consequences and plans for rehabilitation of the landscape. The Society of Environmental Toxicology and Chemistry (SETAC) Latin America Geographic Unit hosted the Fundão Dam Rupture Science Meeting in Brasilia, Brazil, in June 2019 to report on the findings from these studies. Fourteen technical papers from that meeting are presented in this Integrated Environmental Assessment and Management (IEAM) special series. These papers and the technical discussions at the meeting reflect the consensus opinions of scientists who attended the symposium. Delegates generally agreed that society must commit to rehabilitation after disasters based on the best available evidence describing the structure and function of affected ecosystems. Scientists can play a crucial role in prioritizing and facilitating rehabilitation actions, as well as monitoring for progress toward achieving goals. Integr Environ Assess Manag 2020;16:569-571. © 2020 SETAC.

O colapso da barragem de rejeitos de Fundão em novembro de 2015 em Minas Gerais, Brasil, resultou na liberação de aproximadamente 36 milhões de metros cúbicos de partículas do tamanho de argila e areia fina para o meio ambiente. O derramamento se estendeu por mais de 600 km na bacia hidrográfica do Rio Doce, afetou os ecossistemas terrestres e aquáticos e comprometeu as atividades socioeconômicas em toda a bacia hidrográfica. Numerosos programas de monitoramento e pesquisas na bacia, desde então, contribuem para uma melhor compreensão das consequências ambientais e para os planos de reabilitação da paisagem. A Sociedade de Toxicologia e Química Ambiental (SETAC) da América Latina sediou o Encontro Científico sobre a Ruptura da Barragem do Fundão em Brasília, Brasil, em junho de 2019, para relatar os resultados desses estudos. Quatorze artigos técnicos dessa reunião são apresentados nesta série especial da revista Integrated Environmental Assessment and Management (IEAM). Esses artigos e as discussões técnicas do encontro refletem as opiniões consensuais dos cientistas que participaram do simpósio. Os delegados em geral concordaram que a sociedade deve se comprometer com a reabilitação após desastres com base na melhor evidência disponível que descreva a estrutura e a função dos ecossistemas afetados. Os cientistas podem desempenhar um papel crucial na priorização e facilitação de ações de reabilitação, bem como no acompanhamento da evolução do cumprimento das metas. Integr Environ Assess Manag 2020;16:569-571.

CRISPR-TAPE: protein-centric CRISPR guide design for targeted proteome engineering.

Rational molecular engineering of proteins with CRISPR-based approaches is challenged by the gene-centric nature of gRNA design tools. To address this, we have developed CRISPR-TAPE, a protein-centric gRNA design algorithm that allows users to target specific residues, or amino acid types within proteins. gRNA outputs can be customized to support maximal efficacy of homology-directed repair for engineering purposes, removing time-consuming post hoc curation, simplifying gRNA outputs and reducing CPU times.

Ecotoxicological Assessment of the Doce River Surface Water After the Fundão Dam Collapse.

On 5 November 2015, the Samarco Fe ore mining operations released approximately 50 million cubic meters of mining waste into the environment, due to a dam collapse. Aiming at understanding the potential effects on the Doce River, different regions of the course of tailings were monitored using acute and chronic ecotoxicological tests with 4 species: Ceriodaphnia dubia, Daphnia similis, Danio rerio, and Vibrio fischeri. The results showed no acute toxicity for water column organisms. However, chronic toxicity was observed with the tests with the microcrustacean C. dubia, mainly related to the physical effects of the passage of flood wave and increased suspended solids, given that toxicity was reduced after filtering the samples. The results showed different magnitudes of impact among the upper, middle, and lower Doce River, with greater impact close to the dam failure area. Integr Environ Assess Manag 2020;16:608-614. © 2020 SETAC.

Em 5 de novembro de 2015, aproximadamente 50 milhões de m3 de resíduos provenientes da barragem de rejeitos das operações de mineração de minério de ferro da Samarco atingiram o meio ambiente decorrente do seu rompimento. Com o objetivo de compreender os potenciais efeitos sobre o rio Doce, o monitoramento foi realizado, através de testes ecotoxicológicos com quatro espécies de diferentes, das regiões atingidas pela pluma de turbidez. Os resultados demonstraram, de modo geral, ausência de ecotoxicidade aguda para organismos de coluna de água. Entretanto, foi evidenciada ecotoxicidade crônica com o microcrustáceo Ceriodaphnia dubia, que esteve relacionada principalmente aos efeitos físicos da passagem da onda de cheia e ao aumento de sólidos em suspensão na coluna d'água. Os resultados mostraram que a magnitude do impacto foi diferente nas três regiões do rio Doce (alta, média e baixa), com maior intensidade na região mais próxima da área do rompimento da barragem. Integr Environ Assess Manag 2020;16:608-614.

Rio Doce Acoustic Surveys of Fish Biomass and Aquatic Habitat.

Following the failure of the Fundão mine tailings dam in Brazil, approximately 32 million cubic meters of Fe ore tailings were released into the downstream riverine system. The postevent monitoring surveys implemented the use of noninvasive acoustic methods to improve the understanding of the fish biomass distribution patterns and aquatic habitat condition of the impacted reaches of the Rio Gualaxo do Norte, Rio do Carmo, and Rio Doce. The primary focus of the program was to collect hydroacoustic measurements of fish biomass, which was accompanied by sonar imaging of aquatic habitats using high-resolution side scan and downward imaging sonar at each site visited. The biannual surveys began in April 2017 and were fundamentally a multiple control-impact design because before data (prior to the dam failure event) were not available. Up to 22 sites were visited for each survey, including reservoir and river sites. Results indicate similar levels of instream habitat between control and impact river and reservoir sites. Average volumetric biomass was not significantly different between impact sites and their corresponding controls in the August 2018 survey (latest to date). Preliminary temporal analysis of the biomass data set collected indicates that either stable or increasing levels of biomass are detected at tailings impacted sites within the Rio Doce. Integr Environ Assess Manag 2020;16:615-621. © 2020 Hydrobiology QLD Pty Ltd. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Após o rompimento da barragem de rejeitos da mina do Fundão no Brasil, cerca de 32 milhões de metros cúbicos de rejeitos de minério de Fe foram libertados no sistema fluvial a jusante. Monitoramentos pós-evento foram implementados com a utilização de métodos acústicos não invasivos visando ampliar a compreensão dos padrões de distribuição da biomassa de peixes e condições dos habitat aquáticos em trechos impactados do Rio Gualaxo do Norte, Rio do Carmo e Rio Doce. A aquisição de medições hidroacústicas sobre a biomassa de peixes foi o foco principal do programa, seguido pela obtenção de imagens dos habitats aquáticos através da utilização de um sonar de varredura lateral de alta resolução e um sonar de imagem vertical, em cada local visitado. Os levantamentos de campo semestrais tiveram início em Abril de 2017 e seu design amostral foi baseados na concepção "trechos controle - trechos impactados" uma vez que não existem dados disponíveis para o período anterior ao evento (rompimento da barragem). Em cada levantamento foram visitados até 22 pontos de amostragem, incluindo vários reservatórios e rios. Os resultados indicaram níveis de habitat similares entre os pontos controle e impacto, de rios e reservatórios. No monitoramento mais recente (Agosto/2018) a biomassa volumétrica média não foi significativamente diferente entre os locais de impacto e os seus correspondentes pontos controles. A análise temporal preliminar do conjunto de dados sobre a biomassa indicou níveis estáveis ou crescentes deste parâmetro nos locais impactados pelos rejeitos, no Rio Doce. Integr Environ Assess Manag 2020;16:615-621.

FSP1 is a glutathione-independent ferroptosis suppressor.

Ferroptosis is an iron-dependent form of necrotic cell death marked by oxidative damage to phospholipids1,2. To date, ferroptosis has been thought to be controlled only by the phospholipid hydroperoxide-reducing enzyme glutathione peroxidase 4 (GPX4)3,4 and radical-trapping antioxidants5,6. However, elucidation of the factors that underlie the sensitivity of a given cell type to ferroptosis7 is crucial to understand the pathophysiological role of ferroptosis and how it may be exploited for the treatment of cancer. Although metabolic constraints8 and phospholipid composition9,10 contribute to ferroptosis sensitivity, no cell-autonomous mechanisms have been identified that account for the resistance of cells to ferroptosis. Here we used an expression cloning approach to identify genes in human cancer cells that are able to complement the loss of GPX4. We found that the flavoprotein apoptosis-inducing factor mitochondria-associated 2 (AIFM2) is a previously unrecognized anti-ferroptotic gene. AIFM2, which we renamed ferroptosis suppressor protein 1 (FSP1) and which was initially described as a pro-apoptotic gene11, confers protection against ferroptosis elicited by GPX4 deletion. We further demonstrate that the suppression of ferroptosis by FSP1 is mediated by ubiquinone (also known as coenzyme Q10, CoQ10): the reduced form, ubiquinol, traps lipid peroxyl radicals that mediate lipid peroxidation, whereas FSP1 catalyses the regeneration of CoQ10 using NAD(P)H. Pharmacological targeting of FSP1 strongly synergizes with GPX4 inhibitors to trigger ferroptosis in a number of cancer entities. In conclusion, the FSP1-CoQ10-NAD(P)H pathway exists as a stand-alone parallel system, which co-operates with GPX4 and glutathione to suppress phospholipid peroxidation and ferroptosis.

Quality assurance of gating response times for surface guided motion management treatment delivery using an electronic portal imaging detector.

Gating response times of monitoring system/LINAC combinations for gated radiotherapy treatments are notoriously difficult to measure. This difficulty may reflect why the incorporation of gating response times is not thoroughly considered when creating treatment margins for gated radiotherapy treatments, however ignoring the effect of gating response time could lead to significant treatment inaccuracies. This study shows a methodology which measured gating response times for AlignRT/Varian Truebeam combination which appears to be applicable to any surface guided monitoring/Linac combination as well as those combinations which incorporate extended lag times (>200 ms). Beam on lag time appears to be measurably greater than beam off lag time. Although these gating response times are slower than other gating systems on the market, the advantages surface guided radiotherapy (SGRT) could potentially provide for treatment accuracy is discussed as well as demonstrating the lack of guidance regarding SGRT with respect to gated treatments.