Negative Pressure Rooms Research Articles

Serratia marcescens outbreak at a neonatal intensive care unit in an acute care tertiary hospital in Singapore

To report the epidemiological, diagnostic, and genetic investigation of an outbreak of neonatal patients infected or colonized with Serratia marcescens (S. marcescens) including the infection control interventions. Outbreak investigation report. 28-bedded neonatal unit in an acute care tertiary hospital in Singapore divided into three areas: two negative-pressure airborne infection isolation rooms with a shared anteroom, 10 neonatal intensive care unit (NICU) beds, and 16 high dependency beds. A total of five neonates were involved in this outbreak. Screening of in-flight patients and their immediate environment for S. marcescens to determine probable environmental sources, whole genome sequencing (WGS) analysis of resulting isolates to determine clone-relatedness and possible transmission patterns. Implementation of infection control interventions included prompt isolation of cases, enhanced equipment and environmental disinfection, use of alcohol-based hand rub as the preferred hand hygiene mode, enhanced infection prevention orientation for parents, review of practices, audits, and immediate feedback on non-compliance. Five neonates infected or colonized with S. marcescens were involved in this outbreak. Four were infection cases whilst one identified through contact tracing. Three NICU sinks and the milk preparation room sink were tested positive for S. marcescens. WGS confirmed clonality of strains from two NICU sinks, and milk preparation room sink with that of the five neonates. Multiprong strategy was required to contain this outbreak. WGS analysis showed association of biofilms in sinks with the outbreak.

Airflow and Pressure Design Review of Modular Negative Pressure Wards

In the aftermath of the COVID-19 pandemic, the urgent need for the rapid deployment of healthcare facilities propelled the rise of modular construction using an infill approach. In these modular, negative-pressure wards, the design of indoor airflow and pressure plays a crucial role in meeting the ventilation strategies required for isolation facilities. Accordingly, this paper focuses on modular negative-pressure wards employing an infill construction method and proposes an appropriate spatial pressure distribution to address the problem of air tightness degradation due to leakage. This study analyzed the indoor airflow and pressure distribution of a unit module corresponding to an infill. It aimed to examine whether the pressure difference with the adjacent room is maintained and to assess its effectiveness in isolating contaminated air. First, the airflow rate of the heating, ventilation, and air conditioning system in the unit module was calculated to ensure that it would meet the performance criteria of the negative-pressure ward. Afterward, based on the calculated rate, the study assessed the airflow and room-specific pressure within a typical floor, encompassing both the unit module and associated nursing support facilities. Here, the airflow in the external corridor of the typical floor was divided into two cases according to the pressure distribution: negative pressure and atmospheric pressure. The calculation results were compared using a computational fluid dynamics tool. The analysis results confirm that the air isolation performance is adequate as the pressure difference between adjacent rooms in the unit module and the typical floor was maintained at 2.5 Pa. Additionally, the indoor airflow in the negative-pressure isolation room formed a stable flow at a slow speed of 0.1–0.2 m/s, minimizing the possibility of air contamination from outside the isolation room. In particular, Case B of the typical floor design proposes a method to optimize the pressure distribution in the modular negative-pressure ward by designing the ventilation flow rate at atmospheric pressure level. Thus, this study emphasizes that atmospheric pressure design is appropriate when designing pressure in areas where negative-pressure control is difficult and can contribute to the design and improvement of similar medical facilities in the future.

Safety, tolerability, viral kinetics, and immune correlates of protection in healthy, seropositive UK adults inoculated with SARS-CoV-2: a single-centre, open-label, phase 1 controlled human infection study

A SARS-CoV-2 controlled human infection model (CHIM) has been successfully established in seronegative individuals using a dose of 1×101 50% tissue culture infectious dose (TCID50) pre-alpha SARS-CoV-2 virus. Given the increasing prevalence of seropositivity to SARS-CoV-2, a CHIM that could be used for vaccine development will need to induce infection in those with pre-existing immunity. Our aim was to find a dose of pre-alpha SARS-CoV-2 virus that induced infection in previously infected individuals. Healthy, UK volunteers aged 18-30 years, with proven (quantitative RT-PCR or lateral flow antigen test) previous SARS-CoV-2 infection (with or without vaccination) were inoculated intranasally in a stepwise dose escalation CHIM with either 1×101, 1×102, 1×10³, 1×104, or 1×105 TCID50 SARS-CoV-2/human/GBR/484861/2020, the same virus used in the seronegative CHIM. Post-inoculation, volunteers were quarantined in functionally negative pressure rooms (Oxford, UK) for 14 days and until 12-hourly combined oropharyngeal-nasal swabs were negative for viable virus by focus-forming assay. Outpatient follow-up continued for 12 months post-enrolment, with additional visits for those who developed community-acquired SARS-CoV-2 infection. The primary objective was to identify a safe, well tolerated dose that induced infection (defined as two consecutive SARS-CoV-2 positive PCRs starting 24 h after inoculation) in 50% of seropositive volunteers. This study is registered with ClinicalTrials.gov (NCT04864548); enrolment and follow-up to 12 months post-enrolment are complete. Recruitment commenced on May 6, 2021, with the last volunteer enrolled into the dose escalation cohort on Nov 24, 2022. 36 volunteers were enrolled, with four to eight volunteers inoculated in each dosing group from 1×101 to 1×105 TCID50 SARS-CoV-2. All volunteers have completed quarantine, with follow-up to 12 months complete. Despite dose escalation to 1×105 TCID50, we were unable to induce sustained infection in any volunteers. Five (14%) of 36volunteers were considered to have transient infection, based on the kinetic of their PCR-positive swabs. Transiently infected volunteers had significantly lower baseline mucosal and systemic SARS-CoV-2-specific antibody titres and significantly lower peripheral IFNγ responses against a CD8+ T-cell SARS-CoV-2 peptide pool than uninfected volunteers. 14 (39%) of 36 volunteers subsequently developed breakthrough infection with the omicron variant after discharge from quarantine. Most adverse events reported by volunteers in quarantine were mild, with fatigue (16 [44%]) and stuffy nose (16 [44%]) being the most common. There were no serious adverse events. Our study demonstrates potent protective immunity induced by homologous vaccination and homologous or heterologous previous SARS-CoV-2 infection. The community breakthrough infections seen with the omicron variant supports the use of newer variants to establish a model with sufficient rate of infection for use in vaccine and therapeutic development. Wellcome Trust and Department for Health and Social Care.

B-018 Compact all in one, Fully Automated Molecular Diagnostic System “ExiStation™ FA 96” in 100 minutes

Abstract Background Traditional PCR method’s instruments are discrete the processes of sample collection, nucleic acid(NA) extraction, and NA amplification. As human labor is required between the instruments, there is a risk of human error, infection and contamination. Biosafety facilities such as biosafety cabinet, level D protective clothing, and negative pressure facilities are required for ensuring safe testing. To improve the testing environment, the molecular diagnostic market has developed and started using automated instruments, though, which take up larger space and take longer time to test. As a result, it is necessary to develop instrument that takes up less space and reduces testing time to a minimum, so, space and time can be saved. Methods In this study, we developed an automated systematic genetic diagnostic instrument. In order to carry out the entire process within one integrated instrument, automatic mechanism of de-capping and re-capping of sample tube, sample aspiration, and sample transfer were developed. The system also includes integrated key steps of NA extraction and amplification (qPCR). We developed a primer/probe design technology that can accurately detect viruses with high accuracy in performing PCR tests using extracted genes, as well as precision temperature control algorithm and optimized real-time nucleic acid amplification using reverse transcription enzymes and gene amplification enzymes. In order to carry out all these functions within one device, we maximized user convenience by developing software for instrument operation, result analysis, and a Graphic User Interface for automation Results ExiStation™ FA 96 is largely composed of sample processing, gene extraction, and gene amplification (qPCR). (Photo to be in poster) Sample Processing automatically opens a cap of sample tube, then transfer a required quantity of sample to cartridge. While opening the cap, the barcode attached to sample tube is automatically identified and the information required for a test is entered. After sampling, the cap is automatically re-capped and placed back in the sample tube rack. When collecting samples, it measures the sample level in the tube and indirectly check the viscosity by detecting the pressure inside the tip, minimizing aspiration errors. The Extraction step performs the function of extracting genes. It consists of three modules of 32 wells, and the number of samples can even be adjusted in eight units, so the instrument can be operated flexibly upon the number of samples requested. Then, the qPCR step follows. The ExiStation™ FA 96 setup allows simultaneous testing of up to 20 targets for 94 samples in approximately 100 min. The instrument is equipped with a HEPA filter and UV lamp to maintain clean, and since the sample tubes are inserted directly on the instrument, it is no of necessity or save the costs such as of negative pressure rooms, biosafety cabinet, and level D protective clothing. Conclusion ExiStation™ FA 96 is a fully automated molecular diagnostic test instrument that can quickly and accurately process large amounts of samples, while greatly reducing user risks and shortening molecular diagnostic test time.

Negative-pressure rooms and Aspergillus risk-Air balance alone is insufficient.

Negative-pressure rooms and Aspergillus risk-Air balance alone is insufficient.

Efficacy of a surgical mask during high-flow nasal oxygen therapy in preventing aerosol dispersion: a randomized controlled study.

It is not clear whether or not high-flow nasal oxygenation used in patients with severe respiratory tract infection, or coughing, increases the risk of infection to the healthcare personnel, and whether or not applying a surgical mask to the patient's face or treating the patient in a negative-pressure room can reduce the risk. In a randomized crossover design, we compared in 50 participants receiving high-flow nasal oxygenation, the aerosol counts measured at approximately 20cm above the participant's mouth in 32 different circumstances (with or without coughing, with or without wearing a surgical mask, at four different flow rates of oxygenation, in a positive- or negative-pressure operating room). In a positive-pressure room, a surgical mask significantly decreased the aerosol counts during coughing (P = 0.0005), or during no coughing (P = 0.009), under high-flow nasal oxygenation (at 60l.min-1). In the negative-pressure room, the aerosol count was significantly lower than in the positive-pressure room, for all the circumstances (all P < 0.001), and a surgical mask significantly decreased the aerosol counts during coughing (P = 0.047) but not during no coughing (P = 0.60). In conclusion, treating a patient in a negative-pressure room, or applying a surgical mask, during high-flow nasal oxygenation (with the flow rate of 60l.min-1) would inhibit, but would not completely prevent, dispersion of aerosols by coughing.

Gambaran Kunjungan Pasien di Ruang Bertekanan Negatif Semasa Pandemi Covid-19

Background: Dental and oral health is important to maintain a healthy body, the prevalence of dental and oral problems in DKI Jakarta was as high as 59.1% and only 16.4% received services. After the outbreak of Covid-19 pandemic, people felt anxious visiting dentist for fear of being infected. This caused a change in the pattern of patient visit. Objectives: To describe patient visit at RSGM-P USAKTI before and after the operation of negative pressure room. Methods: Descriptive observational study with a cross-sectional design to describe patient visit at RSGM-P USAKTI before and after the operation of negative pressure room in 2019-2021. Results: A total of 21,761 visits were recorded before the pandemic. There was a decrease before (1,472 visits) and an increase (5,929 visits) after the operation of negative pressure room. Female patients were more recorded. During pandemic there was a decrease especially in patients aged ≤11.9 years, number of caries cases increased, and visits after the negative pressure room was operational during the pandemic increased. Conclusion: Patients visit decreased before and increased after the negative pressure room operated. However, counseling regarding the importance of negative pressure rooms to public is crucial.&#x0D;

음압병실에서 공조시스템 급배기 위치 개선에 따른 호흡기 감염병 공기전파 저감 효과 평가

음압병실에서 공조시스템 급배기 위치 개선에 따른 호흡기 감염병 공기전파 저감 효과 평가

Clinical Issues - July 2023.

Use of clean versus sterile pneumatic tourniquet cuffs Key words: clean, sterile, pneumatic tourniquet, incision site, cuff placement. Active shooter crisis preparedness Key words: active shooter preparedness, emergency response, active shooter event, evacuate, barricade. Heating, ventilation, and air-conditioning parameters Key words: laminar airflow (LAF); unidirectional ultraclean air-delivery system; unidirectional downward airflow; turbulent; heating, ventilation, and air-conditioning (HVAC) system. Modifying directional air pressure settings Key words: directional air pressure, negative-pressure room, positive-pressure room, bronchoscopy, parameters.

Association between negative-pressure room utilization and hospital-acquired Aspergillus rates in patients with coronavirus disease 2019 (COVID-19) in two academic hospitals.

Hospital-acquired Aspergillus rates among coronavirus disease 2019 (COVID-19) patients were initially higher at a hospital with high negative-pressure room utilization compared to a similar hospital with low utilization but with otherwise identical infection control policies. After the index hospital decreased negative-pressure utilization, hospital-acquired Aspergillus case rates at the 2 hospitals converged.

Tracheal bifurcation repair for blunt thoracic trauma in a patient with COVID-19

BackgroundTracheobronchial injury (TBI) is a rare but potentially life-threatening trauma that requires prompt diagnosis and treatment. We present a case in which a patient with COVID-19 infection was successfully treated for a TBI through surgical repair and intensive care with extracorporeal membrane oxygenation (ECMO) support.Case presentationThis is the case of a 31-year-old man transported to a peripheral hospital following a car crash. Tracheal intubation was performed for severe hypoxia and subcutaneous emphysema. Chest computed tomography showed bilateral lung contusion, hemopneumothorax, and penetration of the endotracheal tube beyond the tracheal bifurcation. A TBI was suspected; moreover, his COVID-19 polymerase chain reaction screening test was positive. Requiring emergency surgery, the patient was transferred to a private negative pressure room in our intensive care unit. Due to persistent hypoxia and in preparation for repair, the patient was started on veno-venous ECMO. With ECMO support, tracheobronchial injury repair was performed without intraoperative ventilation. In accordance with the surgery manual for COVID-19 patients in our hospital, all medical staff who treated this patient used personal protective equipment. Partial transection of the tracheal bifurcation membranous wall was detected and repaired using 4-0 monofilament absorbable sutures. The patient was discharged on the 29th postoperative day without postoperative complications.ConclusionsECMO support for traumatic TBI in this patient with COVID-19 reduced mortality risk while preventing aerosol exposure to the virus.

Viral emissions into the air and environment after SARS-CoV-2 human challenge: a phase 1, open label, first-in-human study

Effectively implementing strategies to curb SARS-CoV-2 transmission requires understanding who is contagious and when. Although viral load on upper respiratory swabs has commonly been used to infer contagiousness, measuring viral emissions might be more accurate to indicate the chance of onward transmission and identify likely routes. We aimed to correlate viral emissions, viral load in the upper respiratory tract, and symptoms, longitudinally, in participants who were experimentally infected with SARS-CoV-2. In this phase 1, open label, first-in-human SARS-CoV-2 experimental infection study at quarantine unit at the Royal Free London NHS Foundation Trust, London, UK, healthy adults aged 18-30 years who were unvaccinated for SARS-CoV-2, not previously known to have been infected with SARS-CoV-2, and seronegative at screening were recruited. Participants were inoculated with 10 50% tissue culture infectious dose of pre-alpha wild-type SARS-CoV-2 (Asp614Gly) by intranasal drops and remained in individual negative pressure rooms for a minimum of 14 days. Nose and throat swabs were collected daily. Emissions were collected daily from the air (using a Coriolis μ air sampler and directly into facemasks) and the surrounding environment (via surface and hand swabs). All samples were collected by researchers, and tested by using PCR, plaque assay, or lateral flow antigen test. Symptom scores were collected using self-reported symptom diaries three times daily. The study is registered with ClinicalTrials.gov, NCT04865237. Between March 6 and July 8, 2021, 36 participants (ten female and 26 male) were recruited and 18 (53%) of 34 participants became infected, resulting in protracted high viral loads in the nose and throat following a short incubation period, with mild-to-moderate symptoms. Two participants were excluded from the per-protocol analysis owing to seroconversion between screening and inoculation, identified post hoc. Viral RNA was detected in 63 (25%) of 252 Coriolis air samples from 16 participants, 109 (43%) of 252 mask samples from 17 participants, 67 (27%) of 252 hand swabs from 16 participants, and 371 (29%) of 1260 surface swabs from 18 participants. Viable SARS-CoV-2 was collected from breath captured in 16 masks and from 13 surfaces, including four small frequently touched surfaces and nine larger surfaces where airborne virus could deposit. Viral emissions correlated more strongly with viral load in nasal swabs than throat swabs. Two individuals emitted 86% of airborne virus, and the majority of airborne virus collected was released on 3 days. Individuals who reported the highest total symptom scores were not those who emitted most virus. Very few emissions occurred before the first reported symptom (7%) and hardly any before the first positive lateral flow antigen test (2%). After controlled experimental inoculation, the timing, extent, and routes of viral emissions was heterogeneous. We observed that a minority of participants were high airborne virus emitters, giving support to the notion of superspreading individuals or events. Our data implicates the nose as the most important source of emissions. Frequent self-testing coupled with isolation upon awareness of first symptoms could reduce onward transmissions. UK Vaccine Taskforce of the Department for Business, Energy and Industrial Strategy of Her Majesty's Government.

Analysis of parametric optimization on the design of negative pressure room

ABSTRACT Negative pressure rooms are crucial for the prevention of the dispersion of infectious diseases. Using the ANSYS-Fluent finite volume method (FVM), standard kϵ turbulent, species transport, and discrete phase model with the transient condition, this research aims to reduce the amount of airborne contamination inside the negative pressure room. In the current design, both 10 area ratios and static supply pressures 1 – 30 Pa are considered. The optimum condition is reached at an area ratio of 9 and 13 Air change per hours (ACHs) with a 96% reduction in CO2 concentration and an exhaust velocity of 3 m/s and a minimum power consumption of 247 W at a supply pressure of (10) Pa. The effective direct airflow pattern is observed as a safe environment by analyzing the streamlines and velocity vector distributions. To prevent the infectious viruses spread, the particle tracking of coughed droplets is analyzed so that 100% of aerosol particles can be extracted within 3 s. The door-opening effect showed that the desired negative pressure could be maintained even if the door opened for a long time. This work will benefit the design engineers for any intended negative pressure room and provide a secure working environment for the medical personnel.

The Isolation System for Treatment and Agile Response for High-Risk Infections (ISTARI) Unit, a Carecubes Design: Moving PPE Around the Patient, An Assessment of Provider Safety and Infection Control with Emergency Medicine Residents During Simulation

Introduction:The ISTARI unit is designed to be assembled in buildings or field hospitals to provide negative-pressure rooms in low-resource areas and decrease PPE use in the setting of highly-infectious diseases. Each unit is designed to perform ~20 air exchanges/hour with HEPA filters with multiple access points for providers to perform patient care without entering the unit while decreasing overall PPE usage. The goals of the design include patient safety, ease of use for, decreased infectious spread, and unit affordability.Method:A survey was obtained following a medical simulation within the ISTARI unit with Emergency Medicine resident physicians. The case involved an Ebola patient with Ventricular Tachycardia which progressed to cardiac arrest. Teams were given written and video instructions for the ISTARI unit and Ebola-level PPE. They were limited to one set of high-level PPE for the case. The survey scoring was a 0-5 scale, five being the highest.Results:Medical history-taking provider safety (PS)- 2.87, infection control (IC)-3.09, physical examination PS-3.52, IC-3.78, ultrasound usage PS-3.35, IC-3.43, intubation PS-2.35, IC-2.57, CPR PS-3.43, IC-3.65, cardioversion PS-3.35, IC-3.78, and overall average PS-3.145, IC-3.383.Limitations were noted compared with traditional care, but 100% of teams met critical actions for patient management, including intubation, cardioversion, and CPR. GloGerm showed no contamination to those providing care outside the unit, but a small amount of contamination after doffing for those who entered the unit.Conclusion:The ISTARI unit is a cost-effective isolation unit maximizing provider safety in management of patients with highly-infectious diseases, particularly in low-resource settings. It allows for easy mobilization of units and decreased medical supplies waste. The preliminary study shows satisfactory data about provider safety and infection control when using ISTARI for a highly-infectious patient, especially in providers unfamiliar with typical high-level PPE. Providers were able to provide all necessary critical actions for highly-infectious, critically-ill patients.

Viable mpox virus in the environment of a patient room

We conducted a prospective environmental surveillance study to investigate the air, surface, dust, and water contamination of a room occupied by a patient infected with mpox virus (MPXV) at various stages of the illness. The patient tested positive for MPXV from a throat swab and skin lesions. Environmental sampling was conducted in a negative pressure room with 12 unidirectional high efficiency particulate air filter (HEPA) air changes per hour and daily cleaning of the surfaces. A total of 179 environmental samples were collected on days 7, 8, 13, and 21 of illness. Among the days of sampling, air, surface, and dust contamination showed the highest contamination rates on day 7 and 8 of illness, with a gradual decline to the lowest contamination level by day 21. Viable MPXV was isolated from surfaces and dust samples and no viable virus was isolated from the air and water samples.

Assessment of aerosol persistence in ICUs via low-cost sensor network and zonal models

The COVID-19 pandemic raised public awareness about airborne particulate matter (PM) due to the spread of infectious diseases via the respiratory route. The persistence of potentially infectious aerosols in public spaces and the spread of nosocomial infections in medical settings deserve careful investigation; however, a systematic approach characterizing the fate of aerosols in clinical environments has not been reported. This paper presents a methodology for mapping aerosol propagation using a low-cost PM sensor network in ICU and adjacent environments and the subsequent development of the data-driven zonal model. Mimicking aerosol generation by a patient, we generated trace NaCl aerosols and monitored their propagation in the environment. In positive (closed door) and neutral-pressure (open door) ICUs, up to 6% or 19%, respectively, of all PM escaped through the door gaps; however, the outside sensors did not register an aerosol spike in negative-pressure ICUs. The K-means clustering analysis of temporospatial aerosol concentration data suggests that ICU can be represented by three distinct zones: (1) near the aerosol source, (2) room periphery, and (3) outside the room. The data suggests two-phase plume behavior: dispersion of the original aerosol spike throughout the room, followed by an evacuation phase where "well-mixed" aerosol concentration decayed uniformly. Decay rates were calculated for positive, neutral, and negative pressure operations, with negative-pressure rooms clearing out nearly twice as fast. These decay trends closely followed the air exchange rates. This research demonstrates the methodology for aerosol monitoring in medical settings. This study is limited by a relatively small data set and is specific to single-occupancy ICU rooms. Future work needs to evaluate medical settings with high risks of infectious disease transmission.

Theoretical and evidence-based infection control during general anesthesia in the COVID-19 pandemic.

With the outbreak of COVID-19, attention has focused on measures to prevent droplet infection. Operating rooms, where we anesthesiologists mainly work, are equipped with various theories and techniques for performing surgical procedures and general anesthesia on patients with various infectious diseases, whether airborne, droplet, or contact infection, and are an environment where surgical procedures and general anesthesia can be safely performed on patients with compromised immune functions. Here, we describe the anesthesia management standards assuming COVID-19 from the viewpoint of medical safety, as well as the structure for supplying clean air in the operating room and the structure of a negative-pressure operating room.

First case of mpox diagnosed in Queensland, Australia: clinical and molecular aspects.

First case of mpox diagnosed in Queensland, Australia: clinical and molecular aspects.

Health Equity in Sickle Cell Research and Access to Therapy

Health Equity in Sickle Cell Research and Access to Therapy

Aerosol Concentrations During Otolaryngology Procedures in a Negative Pressure Isolation Room

To evaluate the role of a negative pressure room with a high-efficiency particulate air (HEPA) filtration system on reducing aerosol exposure in common otolaryngology procedures. Prospective quantification of aerosol generation. Tertiary care. The particle concentrations were measured at various times during tracheostomy tube changes with tracheostomy suctioning, nasal endoscopy with suctioning, and fiberoptic laryngoscopy (FOL), which included 5 times per procedurein a negative pressure isolation room with a HEPA filter and additional 5 times in a nonpressure-controlled room without a HEPA filter. The particle concentrations were measured from the baseline, during the procedure, and continued until 30 minutes after the procedure ended. The particle concentrations were compared to the baseline concentrations. The particle concentration significantly increased from the baseline during tracheostomy tube changes (mean difference [MD] 0.80 × 106 p/m3 , p = .01), tracheostomy suctioning (MD 0.78 × 106 p/m3 , p = .004), at 2 minutes (MD 1.29 × 106 p/m3 , p = .01), and 3 minutes (MD 1.3 × 106 p/m3 , p = .004) after suctioning. There were no significant differences in the mean particle concentrations among various time points during nasal endoscopy with suctioning and FOL neither in isolation nor nonpressure-controlled rooms. A negative pressure isolation room with a HEPA filter was revealed to be safe for medical personnel inside and outside the room. Tracheostomy tube change with tracheostomy suctioning required an isolation room because this procedure generated aerosol, while nasal endoscopy with suctioning and FOL did not. Aerosol generated in an isolation room was diminished to the baseline after 4 minutes.