Research has shown that youth experiencing homelessness (YEH) face barriers to social inclusion and are at risk for poor mental health. With the COVID-19 pandemic threatening the health, wellbeing, and economic circumstances of people around the world, this study aims to assess the impacts of the pandemic on YEH in Toronto, Ontario, as well as to identify recommendations for future waves of COVID-19.Semi-structured interviews were conducted with YEH  and staff who work in one of four downtown emergency shelters for youth (n = 31) in Toronto, Ontario.YEH experienced both structural changes and psychosocial impacts resulting from the pandemic. Structural changes included a reduction in services, barriers to employment and housing, and changes to routines. Psychosocial outcomes included isolation, worsened mental health, and increased substance use. Impacts were magnified and distinct for subpopulations of youth, including for youth that identified as Black, 2SLGBTQ+, or those new to Canada.The COVID-19 pandemic increased distress among YEH while also limiting access to services. There is therefore a need to balance health and safety with continued access to in-person services, and to shift the response to youth homelessness to focus on prevention, housing, and equitable supports for subpopulations of youth. Research on the impacts of the COVID-19 pandemic has demonstrated the myriad tolls the pandemic has taken on the wellbeing and economic circumstances of people globally . These eAlthough there are numerous causes of youth homelessness, the most common are family conflict, abuse, aging out of the child welfare system and, for youth that identify as 2SLGBTQ+, living with non-affirming families . ResearcAn incipient body of research since the start of the pandemic has confirmed these hypotheses. Quantitative research found significant rates of poor mental health and increased substance use among this population since the onset of the pandemic . AdditioEmerging research has found that the impacts of the COVID-19 pandemic are particularly acute among individuals that face additional inequities by virtue of their identities. Results from a large quantitative study in the United States found that mental health issues have disproportionately occurred in “young adults, Hispanic persons, Black persons, essential workers, and those receiving treatment for pre-existing psychiatric conditions” during the pandemic . ResearcOur study adds to the existing literature by investigating the experiences of youth living in one of four downtown emergency shelters in Toronto, Ontario during the COVID-19 pandemic. The primary objective was to understand the impact COVID-19 had on YEH, including among youth that moved to a hotel for services and those that remained in shelter, and to identify recommendations for future waves of COVID-19.In this paper we present the qualitative findings of a broader, sequential mixed-method study, where the qualitative findings were used to inform the selection of quantitative tools and generate hypotheses to be tested in the second, quantitative phase.This study was reviewed and approved by the University of Toronto Research Ethics Board (RIS Protocol No. 39900). In accordance with COVID-19 research protocols, interviews were conducted remotely, and verbal consent was attained subsequent to thoroughly reviewing the informed consent form with participants and prior to the beginning of the interviews. Participants were allowed to withdraw from the research at any time during the interview and were informed that withdrawal would not affect their ability to receive the incentive associated with participation. To maintain anonymity, participants in this study are identified using unique numerical codes, prefixed by ‘Y’ for youth and ‘ST’ for staff.Interviews were conducted with 45 YEH, ages 16–24, as well as 31 staff who work in one of four downtown emergency shelters for youth in Toronto, Ontario, Canada. Interviews with youth were conducted between January and March 2021, a period which roughly aligned with the city’s third wave of the COVID-19 pandemic. Interviews with staff were conducted slightly earlier, between November and December 2020. Interviews lasted approximately 45 minutes. Recruitment drew on a multifaceted convenience sampling approach, distributing flyers to service providers and disseminating emails to staff who then encouraged participation from both youth and fellow staff members. Snowball sampling was also used, as word of mouth between youth accessing services spurred additional participation. Youth who participated were provided a $50 incentive for their time.Data was collected through semi-structured interviews, which focused on the various impacts the pandemic had on YEH, including their mental health and wellbeing, education and employment, and experiences accessing services. Staff were asked about their own experiences providing services during the pandemic, as well as their perspectives on the wellbeing of their clients. Due to health and safety protocols associated with the COVID-19 pandemic, all interviews were conducted remotely using video conferencing technology or by phone. To address accessibility issues for youth who did not have access to stable WIFI or internet-enabled devices, participants were also able to phone into the interview using a local phone number and secure access code generated by the platform. Interviews were sent to a third-party transcription service, who signed a confidentiality agreement, and were transcribed verbatim.The saturation point was determined using the notion of ‘meaning saturation’, which occurs when “no further dimensions, nuances, or insights of issues can be found” . MeaningInterviews were analyzed inductively using thematic analysis , with asInterviews were conducted by the first and second authors, as well as by two research assistants. All four interviewers had previous experience conducting qualitative interviews, and the second author and research assistants also received additional training from the first author prior to engaging in interviews. The research team was also comprised of researchers from diverse social locations, granting each a different positionality, and therefore degree of ‘insider-status’ —vis-à-viThe impacts discussed most frequently by staff and youth have been organized into two large themes: structural changes caused by the pandemic and the psychosocial implications of the structural changes. The structural changes included changes to the shelter sector, and increased barriers to obtaining employment and housing. These changes resulted in psychosocial effects including increased feelings of isolation and loneliness, mental health challenges, and substance use. Each of these themes is elaborated on below, followed by a discussion of how the pandemic impacted sub-groups of young people, in particular youth that identify as 2SLGBTQ+, Black youth and newcomer youth.Prior to the start of each interview, participants were asked a series of demographic questions. Both the youth and staff samples included participants from a variety of social locations and backgrounds. See Tables When the COVID-19 pandemic hit Toronto’s emergency homeless-service system, it was readily apparent that congregate shelters were insufficient to ward off a public health catastrophe. Under the guidelines of the provincial government and Toronto Public Health, the City of Toronto’s Shelter, Support and Housing Administration Division (SSHA) opened up over 25 temporary spaces, including leasing a series of hotels, in order to move thousands of people to hotels to accommodate social distancing measures . For theAt the onset of the pandemic, agencies were forced to halt all in-person programming that did not provide an essential service, resulting in numerous service closures and, in other cases, a shift to a virtual format. This led to a dramatic reduction in social services available to YEH, including both internally at their agency and externally in the community. In addition, many of the rules at the shelters were tightened (such as granting nights away from the shelter) particularly during lockdowns, which meant that youth were not able to see friends and family regularly.In addition to affecting shelter capacity and access to services, COVID-19 restrictions also shaped the economic context for YEH, increasing both employment and housing precarity. As restrictions were imposed over the course of the pandemic, employment opportunities for many young people were severely reduced. Nearly two-thirds of youth participants indicated that their experiences of employment were negatively affected by the pandemic, including layoffs, difficulty finding work, and heightened precarity among those who were employed. When asked whether COVID-19 played a role in them coming to the shelter, one youth described how they were laid off at the beginning of the pandemic and were not hired back despite the store reopening months later:“I was working full time in a management position. I had a lot of responsibilities for the overall managing of the store, and then I just got laid off out of nowhere, and the store was closed for a few months and then it opened, and they didn’t hire me back, and then it closed again.” [Y041].For YEH who were unemployed, finding work was also a challenge. As several youth pointed out, the economic consequences of the pandemic and ensuing restrictions disproportionately affected segments of the economy that typically hire young people, including accommodation, retail, and food service. With these businesses temporarily closed or operating with reduced staffing, employment opportunities were scarce. For one youth, the easing of restrictions—which roughly preceded the pandemic’s ‘waves’—provided some hope, but the resurgence of the virus made it difficult to secure stable work:“…It’s hard to find anything now, because positions are filled. Not many places are accepting new hires and a lot of services are closed, other than essential. Things opened up for a second wave, and that’s when I decided to reapply, but then it went back, so…” [Y008].Among youth who were able to work during the pandemic, the majority were concentrated in precarious jobs, often working in the ‘gig economy’ as couriers for food delivery apps. One youth who worked in this sector described an oversaturated labour market in which it was hard for him to secure gigs:“I have sometimes, just when Uber Eats—like I can’t really make as much, because there’ll be weeks that I couldn’t even make 500 bucks… like not even 300, because there is like so many drivers out there.” [Y017].For some youth, the lack of employment opportunities left them feeling “stuck”, or unsure how to move forward in their lives as they were unable to save money to obtain housing or leave the shelter. Elaborating on this heightened housing precarity, one youth said:“It’s definitely been hard because I have no income coming in. It’s just difficult, not knowing how I’m going to move forward.” [Y002].In addition to facing difficulties saving for housing, the high levels of unemployment and precarious work among youth in the sample led to some losing their housing alongside work. For one youth, moving to the shelter was a direct result of lost employment after restaurants first shut down:“I had my own place; I lived downtown for more than one and a half years, nearly about two years […] 24th March or 25th March [my work] closed due to COVID… After that I haven’t got any job, so have, I did a program, that’s the job training program, but no luck with that too.” [Y023].Prior to coming to shelter, youth and staff also shared how the pandemic encouraged youth to endure unstable and—at times—unsafe living arrangements, often due to a perception of the relative unsafety of the shelter system. As one staff noted, this was particularly prominent among female-identified and trans youth:“Especially for our … for young women and our trans community. They will move in with partners or parents, family systems, because they’re so lonely, or they’ve lost their employment and can’t pay their damn rent, that they go back into family systems and relationship systems that are highly toxic, and sometimes physically abusive.” [ST012].For those who sought to move to shelter during the pandemic, some faced obstacles when looking for a shelter space. As previously discussed, shelter capacity was greatly reduced at the start of the pandemic to accommodate social distancing, and other health and safety protocols were put in place that altered how services were delivered. Moreover, in the event of an outbreak (two or more positive COVID-19 cases among residents or staff), agencies were not permitted to accept new intakes until it was declared safe to do so. One youth shared how these changes made it difficult to find a bed: “it was not easy I can tell you that … just getting in and trying to find a bed” [Y011].One of the most frequently discussed impacts of the pandemic by both youth and staff participants was the reduced access to important social networks, and an associated increase in feelings of isolation and loneliness. Due to health and safety protocols intended to stop the spread of COVID-19, many common spaces were closed, in-person group activities were cancelled, and social distancing and single-occupancy bedrooms were enforced throughout the youth shelter system. Many youth also described not being able to see loved ones, including family and friends, and simply staying in their rooms alone all day. For instance, one said:“I’m a very social person and I love being around people and getting to know people … Like right now, because of like everyone’s at home, because of lockdown and you can’t really like meet people, meet up with friends and stuff, it’s … it’s a very challenging moment, it’s testing me, another limit of me.” [Y017].Staff also observed experiences of isolation in the youth they worked with. One staff described experiencing “heartbreak” after hearing one youth say, “‘I always knew I was alone, [and] now it really looks like I’m alone’,” and described that “This was not the first time I’ve heard it…and it’s not the tenth” [ST012], emphasizing how many youth she heard similar sentiments from. Some staff worried that feelings of isolation were particularly prevalent among the youth at the hotel, given the limited number of staff onsite and a layout that was not conducive to socializing. In the words of one staff member, this only worsened under government-mandated lockdown measures: “At the hotel, we’re really struggling with young people that are also isolating … And with lockdown, that just increases, as well” [ST015]. Connecting youth’s tendencies to stay in their rooms with feelings of hopelessness, the same staff member described how a lack of motivation and routine contributed to isolating habits: “They tend to just isolate … the big question is, what are they getting up for, right?” [ST015].Given the increased unemployment, change to daily routines, and feelings of isolation—on top of continued homelessness—it is not surprising that staff and youth participants consistently mentioned the negative consequences the pandemic has had on YEH’s mental health. These experiences with poor mental health included both worsening mental health issues among those previously diagnosed, as well as a general increase in incidences of anxiety and depression among youth. One staff member described how social and economic aspects of the pandemic also led to decreased mental health because it replicated many of the YEH’s histories of trauma:“I’ve had many, many young people tell me that this entire pandemic mimics trauma for them. It mimics how hopeless they felt, how afraid they felt and how alone they felt, and how they had nowhere to go…[they say] ‘this reminds me exactly of when I was the most alone in my life’. So not having employment opportunities, not having relationships–we know this is a recipe for tremendous stress and a reopening of trauma, which leads to a decline in mental health for sure.” [ST012].Some youth also described seeking hospitalization to cope with their mental health, in part due to a lack of other available options for support. Describing how the effects of isolation intensified mental health issues he experienced, one youth said:“When the pandemic started that’s when I was–I had to go to the hospital for my mental health … I was inside the house, you know, too much that I, I went a little bit crazy.” [Y045].The increase in mental health concerns was described, particularly by staff, as being compounded by a decrease in supports and services during the pandemic. One staff member said:“What really impacted our young people was the pulling of resources. Programming. So, they don’t have anywhere to go, they don’t have anything to do, and they don’t really have any connections they can safely seek. And what we started seeing was a direct impact on an increase in anxiety, increase in depression, and increase in [substance] use.” [ST011].In addition to exacerbating pre-existing mental health issues, others described the ways the pandemic led to an increase in anxiety and depression among youth in the shelter system more broadly. For one staff member who observed these mental health impacts throughout the pandemic, these outcomes were situationally dependent, associated with case numbers and restrictions and compounded as the pandemic stretched to the point of interminability: “I have really also seen their wellness go up and down with the numbers and the amounts of lockdowns and restrictions that we’ve had” [ST012].Underlying many of the pandemic-related mental health effects was a sense of hopelessness. As the pandemic stretched beyond the first wave with no foreseeable end, youth in the sample—and the staff who worked with them—described how they had a hard time envisioning or working towards their life goals. For one youth, COVID-19 made him feel hopeless about his living situation and prospects of leaving the shelter. When asked where he might move after his time at the shelter, he said:“I’m just living day by day at this point, and that’s the shitty part. That’s what makes me feel like I’m a shelter kid and I hate that. I feel like I’m in a revolving door and COVID definitely made it spin a lot faster.” [Y008].While not discussed by many youth participants, staff described a marked increase in substance use among YEH during the pandemic. For many staff, this increase in substance use was perceived to be related to heightened mental health concerns and boredom:“Mental health got really bad in that capacity around isolation, and people got bored and people needed to self-medicate so they would use substances more.” [ST003].Indeed, several staff and three youth noted that people were using substances more, sometimes “all day” simply because there was nothing else to do. One staff suggested that this was even the case for youth who did not use substances prior to the pandemic, as they were “experimenting to see if they were helpful to get through [the pandemic]” [ST017]. In other cases, staff felt that youth who were working to moderate the volume of substances they used prior to the pandemic—due to the loss of employment or other meaningful activities—gave up on this moderation because they “had nothing to stay as clean as possible for” [ST012]. For some youth with more severe addictions, the decrease in daily structure and available supports was described as making it difficult to remain sober. In the words of one staff:“[My client is] a severe alcoholic who had a routine to stay sober including going to the gym, going for coffee with their sponsor, going to an agency for support…all of that was gone. A lot of things are virtual, but you don’t get the human connection. [So they are struggling with] ‘how am I not going to drink? I can’t go to my AA meeting; I can’t go meet my sponsor’.” [ST012].A few staff described an increase in overdoses on site during the pandemic, which is congruent to the opioid crisis facing much of North America, and the toxic drug supply circulating Toronto . One staStaff participants also discussed the additional impacts the pandemic has had on subpopulations of YEH. A few staff, for instance, referred to a gap in the Toronto youth emergency shelter system for Indigenous youth, or the relatively small amount of culturally appropriate or safe spaces for them. One commented that, at their shelter, they do not see a lot of Indigenous youth and felt that this was due to the lack of Indigenous staff employed at the agency. In their words, this staffing gap “doesn’t allow for Indigenous youth to have anyone to identify with” [ST019]. One staff who works closely with youth with developmental disabilities commented that the closure of services as well as the shift to virtual services disproportionately affected these youth, as they often cannot be accommodated online. In this research, however, the most frequently discussed sub-populations were Black youth, newcomer youth, and youth that identify as 2SLGBTQ+, and as such are elaborated on below.Multiple staff and a few youth discussed how systemic racism coupled with the pandemic magnified the impact on Black YEH. One staff member said:“People of Colour already have to deal with structured racism and all the issues that go with that in society. So just imagine, what’s happened with COVID has made things worse.” [ST020].As highlighted earlier, the pandemic greatly affected the ability of study participants to secure employment and housing. This was particularly true for Black youth; several staff described how their Black clients face discrimination from landlords, giving examples of youth discussing units by phone or online, only to be told the unit is no longer available when they meet in person and the landlord sees that they are Black. One staff described the experience of a youth facing blatant racism by a landlord:“I had a client last week who told me that the landlord asked for first and last [rent]…when the youth went to get the keys and the landlord realized it was a person of colour because they had done everything online, they said, ‘you know, I don’t rent to [offensive racist slur]’.” [ST021].In addition, given the changes in daily routines and activities, and associated increase in boredom among youth, it was not uncommon for shelter staff to encourage youth during the warmer months to go outside. This has different implications for Black youth, who are policed differently, both formally and informally, compared to White people . One sta“With nothing to do, even going outside to hang out can cause stress. I have a couple of clients who are young Black men, and they addressed me because staff were telling them ‘maybe go for a walk, get some fresh air’, and they both came back to me on separate occasions [and said] ‘do you understand what it is to hang out if you’re a young Black man? You can’t just sit somewhere and loiter. That’s what’s what they call it, it’s not chilling, it’s loitering’.” [ST012].The pandemic was also the backdrop of a series of public displays of police brutality against unarmed Black citizens, including the murder of George Floyd, and the ensuing protests and public demands for racial justice and police reform. While these events were horrific and attracted widespread condemnation, they were particularly felt by those who identify as Black, as it was described by staff participants as bringing up their own traumatic experiences of racism and experiences with police coupled with the knowledge that they too could experience such tragedy. As one staff elaborated: “From the females it came from a place like that could be my brother. From the males, it was that could be me” [ST022]. This was supported in this study, with Black staff and youth describing the trauma they experienced as a result of these horrific events. One staff member said:“The psychological trauma, right? You’re seeing state sanctioned violence. I mean I know it’s in the States, but we know it happens here. We see it, and we feel it.” [ST021].While staff interviewed stated that the events were acknowledged by leadership at their respective organizations, the general sentiment was that it was insufficient and the impact was not (nor could be) understood by White staff and leadership. A few youth commented that the events were not widely discussed in shelter, and one felt that “COVID took precedence while social justice issues were swept under the rug” [Y014].The impact of the pandemic was also acutely experienced by newcomer youth in Toronto’s shelter system. Most prominently, the process of obtaining status in Canada was drastically slowed down, and many were left with no access to work or study permits and no way to secure an income. One youth shared his story, including how his impeded access to refugee status was extremely trying on his mental health:“This pandemic, it’s affecting me a lot…because my first time in Toronto, I applied for my refugee claim and the second day, the lockdown started. I have nothing to do. I don’t have my working permit, my study permit, nothing. Just read some books and watch some news…In one month it’s going to be one year I’m here; I’m not working, I’m not studying. It’s affecting me.” [Y030].It is worth noting that even among those who had obtained a work permit or legal status, similar to the experiences described above for Black youth, the intersection of the pandemic with structural racism created increased hardship for racialized newcomers. One youth participant who identified as a Muslim Person of Colour described experiencing racism before he even met with an employer:“Although COVID plays a big role in this, me being Muslim, because when they see my name…they don’t really check my resume. I did this before: I went to the same place, I handed in two resumes, everything the same, just a different name and I got called for the other name–the fake one I gave them.” [Y017].Several staff in this study discussed the effects of the pandemic on youth that identify as 2SLGBTQ+. In particular, staff described increased isolation, citing the reduced access to identity-specific services and safe communities. One staff said:“…a lot of community services have provided opportunities for that kind of peer support, social groups, recreational groups. All that stuff has been on pause since the pandemic hit…So I think they’re feeling it the hardest in terms of feeling isolated and disconnected.” [ST004].Expanding on this, a few staff expressed this disconnection was felt in particular among the trans youth they served:“Our trans youth…there aren’t many spaces in our society where they can gather as a mutual people and feel safe to have conversations and be free to express what they need to express…All of those kinds of support systems have gone virtual”–some really made great attempts, but isn’t the same.” [ST012].Similarly, youth participants who identified as 2SLGBTQ+ described experiences of isolation and expressed a desire for more identity-specific supports. In the words of one YEH who identified as trans, isolation was a particularly challenging aspect of the pandemic: “It’s definitely been very isolating unfortunately. Because of course, you can’t see people… So, it’s been hard on my mental health for various reasons” [Y002]. For another youth who identified as non-binary, accessing services over the phone was not always comfortable and, in one instance, forestalled access to gender-affirming support. After describing successfully renewing their health card over the phone, they shared their discomfort at discussing changing their gender on their passport over the phone:“At the same time, some other services, like information sessions or… I wish there was a mix of both in person or online. Because of COVID in-person is not possible. I really wanted to know about some information about changing my sex on my passport to an X, and I just didn’t feel comfortable talking about that over the phone, I would prefer to meet in person and talk about it in person.” [Y041].In this paper we showed that the restrictions of the COVID-19 pandemic led to multiple impacts on YEH, resulting in reduced wellbeing among a population already vulnerable to poor mental health as result of their exposure to adverse childhood experiences and the traumatic experience of being homeless . We discIn light of structural changes caused by the pandemic, YEH faced profound psychosocial impacts. Youth who had no activities to fill their days were faced with feelings of boredom, which while seemingly innocuous, has been correlated with anxiety, depression, and substance use ,34. Yan The findings of this study corroborate similar research studies with YEH in Canada and the United States. Indeed, previous quantitative research has found heightened anxiety, depression, substance use, and sleep disturbances among YEH during the pandemic ,37. SimiThis research also highlighted the additional effects the pandemic had on various subpopulations who disproportionately experience youth homelessness, particularly youth that identify as Black, 2SLGBTQ+, and newcomer youth. Liu & Modir  have argStaff also expressed concerns about youth that identify as 2SLGBTQ+ as they were faced with reduced access to affirming communities and social supports and thus experienced increased feelings of isolation. Service providers must be particularly vigilant in providing outreach and support to youth that identify as 2SLGBTQ+ as research has shown that 2SLGBTQ+ young people are more likely to experience mental health distress, including depression suicidal ideation ,42 and tFinally, the needs of newcomer youth were discussed in this study, mainly how the pandemic prolonged their ability to obtain legal documents and earn an income. Many newcomer youth interviewed discussed how this created profound stress in their lives, as many were trying to raise money to support themselves as well as family members in their country of origin. Even for those with legal status, newcomer youth of colour in this study also spoke about experiencing discrimination when trying to obtain a job, which is also evidenced by other research ,45. WhilIn addition to the structural and psychosocial consequences of COVID-19 on YEH, the closure of services or move to virtual formats meant that, for many, this increase in distress was also met with a decrease in access to supports. While it is vital to respond to the public health crisis, the rise in mental health concerns and acuity, coupled with the inequitable access and varied levels of comfort in receiving virtual services , also points to the need to ensure balance between containing the virus and ensuring youth have access to some in-person services and supports. It is clear from this research, therefore, that social restrictions, and a shift to online services disproportionately impact the most marginalized, and measures need to be in place to support them when they need it the most.Finally, it critical to discuss the effects of the pandemic on YEH with a larger view to the socioeconomic context in which they exist . The YEHThe pandemic has further highlighted how inadequate housing creates profound health inequities. Indeed, many of the public health directives issued during the pandemic—the stay-at-home order for instance—are predicated on the assumption that one has a home to stay at. Similarly, maintaining social distance is exceedingly difficult when one must live with dozens of other youth and staff. Scholars from the Canadian Observatory on Homelessness have been leaders in arguing for a vastly different response to youth homelessness in Canada that focuses on prevention, rapid re-housing and long-term sustainable exits from homelessness ,52,53. TThere are limitations to note about this research. Given the cross-sectional nature of the interviews, which were conducted between November 2020 and March 2021, findings need to be regarded in their temporal context and do not reflect the changing circumstances of future ‘waves’ of COVID-19, nor the cumulative effects these waves may have had on YEH and shelter staff. As an exploratory qualitative study, the findings are also not generalizable to the broader population and future quantitative and mixed methods research on the impacts of the pandemic on YEH is warranted.Additionally, restricting participation in the study by conducting interviews exclusively over the phone and using video-conferencing technology—as per COVID-19 safety protocols—may have introduced a degree of selection bias in the sample. Not all YEH have access to phones, reliable Wi-Fi, and/or Wi-Fi-enabled devices, making it more difficult for these youth to participate in the study. Indigenous youth were also underrepresented in the sample of YEH, leading to a dearth of data on their pandemic experiences. Future research, centred on the experiences of Indigenous YEH during the pandemic, is warranted to address this gap in the literature and highlight the experiences of this subpopulation. Similarly, female-identified youth were also underrepresented in the sample, and the ways in which the pandemic may have had differential impacts on female-identified and non-binary YEH are not documented in the present study. Additional research on the gendered impacts of the pandemic for YEH would begin to address this gap. 28 Feb 2022 <div> PONE-D-22-01338 </div>  <div> “I feel like I’m in a revolving door, and COVID has made it spin a lot faster”: The impact of the COVID-19 pandemic on youth experiencing homelessness in Toronto, Canada </div>  <div> PLOS ONEDear Dr. Noble,Thank you for submitting your manuscript to PLOS ONE. 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Please note that Supporting Information files do not need this step.While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool,  4 Apr 2022Thank you to the editor and reviewers for your thoughtful comments on our manuscript. We address each of the comments in greater detail below. If there are any other comments or points that arise during the review process, please let us know.Journal Requirements:1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. a. The manuscript has been revised to conform to PLOS ONE’s style requirements, and the file names have been updated for this resubmission. Apologies for this mistake. 2. We note that you have provided funding information. However, funding information should not appear in the Funding section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form. Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. a. All funding-related text has been removed from the manuscript. The funding statement provided in the online submission form is accurate and up-to-date, and does not need to be updated.3. In your Data Availability statement, you have not specified where the minimal data set underlying the results described in your manuscript can be found.a. We have modified our data availability statement and added the University of Toronto’s Social Science Ethics Review Board as the contact for anonymized data. The revised statement is as follows:ethics.review@utoronto.ca, +1 (416) 946-3273.”“Data cannot be shared publicly as participants did not consent to the release of transcripts in a public domain. In addition, interview data holds sensitive information from youth experiencing homelessness and the staff who serve them in Toronto, Ontario. These populations are small, and thus publicly sharing data would compromise the level of risk of participating in the research—particularly given the marginalization that youth experiencing homelessness already experience and the ways in which staff discussed their places of employment. Researchers who wish to access anonymized interview data are encouraged to contact the University of Toronto’s Social Science Research Ethics Board to request access at Additional Editor Comments:1. The manuscript is too long, try to shorten it. a. We have substantially revised the manuscript to reduce the length. As a result, we have reduced the word count of the body text from 8641 words to 6710.2. Use continuous line numbers (do not restart the numbering on each page).a. Apologies for this. Continuous line numbers have been added to the manuscript.3. Table 1 and Table 2 are results, not methods. So, remove them from methodology section and add them to results section.a. Thank you for pointing out this mistake. Tables 1 and 2 have been moved to the results section.AttachmentResponse to Reviewers.docxSubmitted filename: Click here for additional data file. 21 Jul 2022 <div> PONE-D-22-01338R1 </div>  <div> “I feel like I’m in a revolving door, and COVID has made it spin a lot faster”: The impact of the COVID-19 pandemic on youth experiencing homelessness in Toronto, Canada </div>  <div> PLOS ONEDear Dr. Noble,Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.plosone@plos.org. 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For instructions see: We look forward to receiving your revised manuscript.Kind regards,Baltica Cabieses, PhDAcademic EditorPLOS ONEJournal Requirements:Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.[Note: HTML markup is below. Please do not edit.]Reviewers' comments:Reviewer's Responses to Questions <font color="black"> Comments to the Author </font> 1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.Reviewer #1: (No Response)Reviewer #2: (No Response)********** <font color="black"> 2. Is the manuscript technically sound, and do the data support the conclusions? </font> The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: PartlyReviewer #2: Yes********** <font color="black"> 3. 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Is the manuscript presented in an intelligible fashion and written in standard English? </font> PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.Reviewer #1: YesReviewer #2: Yes********** <font color="black"> 6. Review Comments to the Author </font> Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. Reviewer #1: Introduction is clear and presents background that justifies the research problem and the relevance of the research. The methodology is clear and rigorously presented, it is suggested to explain an ethical section where the approval of the ethics committee and the verbal informed consent given by the participants are mentioned, given the vulnerability of the study population. The presentation of results and discussion is clear and attractive. When the case of 2SLGBTIQ+ youth is presented, it is recommended to have first-person quotes from their experience, not only focused on the discourse of the shelter workers. It would be interesting to include a reflection from the gender perspective on the women experience who participated less than man in the study. It is suggested to share the limitations of the study in the discussion section if they exist. In the final list of references the year of publication corresponds to the APA style, it is needed to change the references to Vancouver format.Reviewer #2: Congratulations on a very interesting study that will surely contribute to asses and mitigate the impacts of the COVID-19 pandemic on the youth experiencing homelessness. It is a substantial contribution that the results are detailed according to the differentiated experiencies of subpopulations.Some minor aspects could be improved in the manuscript, which will be discussed below.Regarding the sections where the experience of subpopulations is developed, the one that adresses the 2SLGBTQ+, lacks the perspective of the 2SLGBTQ+ population interviewed, as only staff quotes were incorporated.Also, according to the consolidated criteria for reporting qualitative research, an identification should be added to each quotation, for example, a participant number (protecting the anonimity of the participants).Along the report, some minor language editing is required, for example, with repeated words like "support" and "impacts".Finally, a few format aspects should be adressed, like the size of the numbers in the references and the incorporation of page numbers.********** <font color="black"> 7. 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Please note that Supporting Information files do not need this step. </div> While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool,  2 Aug 2022We are very grateful to the editor and reviewers for your thoughtful comments on our manuscript. We address each of the comments in greater detail below and in our 'Response to Reviewers' document. If there are any other comments or points that arise during the review process, please let us know.Reviewer #1’s comments:1. It is suggested to explain an ethical section where the approval of the ethics committee and the verbal informed consent given by the participants are mentioned, given the vulnerability of the study population.a. Thank you for this comment. We have added a subsection on research ethics to the methodology section of the manuscript where we detail the study’s ethics approval and the verbal informed consent process.2. When the case of 2SLGBTIQ+ youth is presented, it is recommended to have first-person quotes from their experience, not only focused on the discourse of the shelter workers.a. This is a very important point raised by both reviewers. The section on 2SLGBTQ+ youth’s experiences has been updated to include quotes from 2SLGBTQ+ youth themselves, who describe experiences of isolation and difficulty accessing services.3. It is suggested to share the limitations of the study in the discussion section if they exist.a. The manuscript has been updated to include a section on limitations alongside the discussion. This section addresses the study’s limitations and suggests potential areas for future research. 4. It would be interesting to include a reflection from the gender perspective on the women experience who participated less than man in the study. a. Thank you very much for this comment. While an analysis of the gendered impacts of the pandemic for youth experiencing homelessness is important, it is unfortunately a limitation of this study given the interview protocol and sample. We have added this as a limitation in the limitations section of the manuscript and call for future research to address this gap.5. In the final list of references the year of publication corresponds to the APA style, it is needed to change the references to Vancouver format.a. The reference list has been updated to be consistent with the Vancouver citation style guide.Reviewer #2’s comments:1. Regarding the sections where the experience of subpopulations is developed, the one that addresses the 2SLGBTQ+, lacks the perspective of the 2SLGBTQ+ population interviewed, as only staff quotes were incorporated. a. Thank you for this very important comment. As mentioned above, we have added quotations from 2SLGBTQ+ youth to this section, where they share first-hand their experiences of isolation and difficulty accessing supports. 2. Also, according to the consolidated criteria for reporting qualitative research, an identification should be added to each quotation, for example, a participant number (protecting the anonymity of the participants). a. The manuscript has been revised to include unique participant codes for each quotation. Quotes from youth are prefixed by ‘Y’, and quotes from staff are prefixed by ‘ST’. This coding formula is described in the methods section of the manuscript.3. Along the report, some minor language editing is required, for example, with repeated words like "support" and "impacts". a. Thank you for catching this. The manuscript has been revised to minimize repeated words.4. Finally, a few format aspects should be addressed, like the size of the numbers in the references and the incorporation of page numbers. a. The reference list has been edited for consistency in font size.AttachmentResponse to Reviewers.docxSubmitted filename: Click here for additional data file. 10 Aug 2022“I feel like I’m in a revolving door, and COVID has made it spin a lot faster”: The impact of the COVID-19 pandemic on youth experiencing homelessness in Toronto, CanadaPONE-D-22-01338R2Dear Dr. Noble,We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at onepress@plos.org.If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact Kind regards,Baltica Cabieses, PhDAcademic EditorPLOS ONE 12 Aug 2022PONE-D-22-01338R2 “I feel like I’m in a revolving door, and COVID has made it spin a lot faster”: The impact of the COVID-19 pandemic on youth experiencing homelessness in Toronto, Canada Dear Dr. Noble:I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. onepress@plos.org.If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact plosone@plos.org. If we can help with anything else, please email us at Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staffon behalf ofDr. Baltica Cabieses Academic EditorPLOS ONE


Periodic boundary conditions (PBCs) are a standard featureof molecularsimulations, and their mathematical and computational aspects arewell-understood and relatively straightforward. However, they canin practice be a nuisance when simulating heterogeneous systems, especiallywhen different types of molecules change their relative positionsduring the simulation. Although the translation required to fix abroken molecular complex of interest can in most cases be easily inferredby visual inspection, it typically depends on the type of system,its configuration, and the box geometry, making automated proceduresproblematic. We present here a general algorithm, named FixBox, thatcan fix a molecular complex of interest from a minimal set of definitionsof its assembling parts and intended arrangement in the simulationbox. It uses a unified triclinic framework for the box geometric periodicity,does not require a full molecular topology, and is applicable to varioustypes of systems and configurations, making it possible to fully andeasily automate the fixing of a broken molecular complex. The performanceof the algorithm is illustrated with problematic configurations ofvarious types of simulated systems. The presented formal frameworkcan generally be useful for algorithms that need to perform geometricaltransformations on systems with PBCs. Or, if we prefer to focus our attentionon the reference box used by the simulation softwarebeing employed , any atom that exits the referencebox through one of its faces can be regarded as effectively reenteringthrough the opposite parallel face. Regardless of the interpretation,PBCs make possible the avoidance of surface effects caused by interactionwith actual box walls and have become the standard approach for simulatingcondensed-phase systems.Molecular simulationsare typically performed using periodic boundaryconditions (PBCs), meaning that the simulation box can be regardedas surrounded by identical replica boxes in a face-to-face arrangementthat fills the whole three-dimensional space.minimum image (MI) distance vectors,2 but this is not alwayspossible . In general, any procedure that requires the molecular complexto be a properly assembled object inside a single box, including simplevisualization, becomes problematic.However, although their mathematicaland computational aspectsare well-understood and relatively straightforward, PBCs can in practicebe a nuisance. The problem is that the adoption of PBCs correspondsessentially to regard the system as homogeneous with respect to translations,a view that may not be the most suitable when dealing with heterogeneoussystems in which some parts are inherently of more interest than others.In particular, in biomolecular simulations, there is typically somekind of molecular complex on which we want to focus our attentionand which is initially centered or somehow properly positioned inthe reference box; for example, a solvated multi-subunit protein wouldbe well-assembled and placed at the box center, a membrane proteinwould be at the center of a horizontal membrane vertically alignedwith the box midpoint, etc. However, as the simulation proceeds, themolecular complex may move across the box faces and end up no longernicely encompassed within the reference box but rather “broken”across its faces; for example, a multi-subunit protein that movesto a box corner may end up with its subunits scattered at variousbox corners, a membrane bilayer that moves up or down may end up withits leaflets at opposite box sides, etc. Of course, this “breaking”with respect to the reference box is to be expected and can be dealtwith transparently in some analyses by using 4). Standard simulationpackages often have tools that partially address this kind of problem, but they usually require beingused in combination with additional procedures  and depend on a full molecular topology thatmight be software-specific (meaning that using such a tool may requirea full topology conversion); there are also some lipid-oriented toolsthat can identify distinct lipid aggregates, but they are not intendedto rearrange the system into the reference box.8 Therefore,it would be convenient to have a more general and easy-to-use algorithm.In order to fix the molecularcomplex, making it again nicely encompassedby the reference box, an obvious initial step is to keep molecularintegrity. This can be easily done using the bond connectivity informationand is often included in simulation software, which can generate coordinatefiles with whole molecules arranged in a simple way . However, theresulting arrangement of the molecular complex, now consisting ofwhole molecules, will generally remain broken across the referencebox. In order to finish fixing the system, we need to perform a translationthat makes the complex to be nicely encompassed by the reference boxwhile keeping PBCs. In fact, the required approximate displacementis usually quite obvious upon visual inspection , but determining the exact translation isin practice system-dependent and can seldom be obtained from a simpleuniversal recipe. A simple standard approach is to start by superimposingthe system on a previously built one in which the complex of interestwas properly assembled and positioned in the reference box, but thiscan easily fail if some parts of the complex have changed their relativearrangement 1. TherefAlthough one generally wants the molecular complexof interestto be centered in the reference box, the crucial step of an efficientalgorithm is the complex assembly rather than its centering. In fact,a multi-part object is necessarily ill-defined when using PBCs, requiringa proper consideration of the MI proximity between its parts . It turns out that, upon visual inspection, we caneasily determine how the parts can be assembled in a proper way becausewe actually know which relations between the parts are sensible andwhich ones are not. Therefore, we mentally perform a sequence of sensibleassembly operations , and only after thatdo we think about the global translation needed to center the assembledcomplex into the reference box and, finally, about the individualPBC-complying translations that would bring each of the remainingmolecules into the reference box. The algorithm proposed here, namedFixBox, tries to simply follow the same sequence of geometric operationsthat we seem to instinctively perform in our mind when visually inspectinga simulation box: (1) evaluate the MI-proximities between the moleculesconstituting the molecular complex of interest; (2) assemble togetherthose molecules based on the MI-proximities; (3) center the resultingassembled system in the reference box; and (4) apply any requiredindividual translations to bring other molecules into the referencebox. For simplicity, it is assumed that the provided atomic coordinatesalready preserve molecular integrity . In addition to proposingthe FixBox algorithm, the present article provides a general formal/mathematicalframework that can be useful for algorithms that perform geometricaltransformations on systems with PBCs; so far, the description of suchalgorithms has mostly been limited to textual descriptions or to theactual source code, which can lead to misunderstandings or be impractical.22.19 Of these, only some regularforms of the parallelepiped (cube and right-rectangular prism), theregular rhombic dodecahedron, and the regular truncated octahedronare common as simulation boxes.10 However, the resultingfive types of space-filling arrangement of polyhedra are just alternativeways of splitting the space, and they can all be expressed in termsof the more general parallelepipedic or triclinic lattice.11 Therefore, for simplicityand uniformity of treatment, it is assumed here that the referencebox is parallelepipedic/triclinic; transformation to and from themore traditional box shapes can be done using available software tools.There are only fivepossible types of space-filling convex polyhedra that can be usedas simulation boxes with PBCs, the so-called parallelohedra: parallelepiped,rhombic dodecahedron, truncated octahedron, hexagonal prism, and rhombo-hexagonaldodecahedron.b1, b2, and b3, called primitive vectors.12  Given an initial point, the primitive vectors can be used asdirected edges that generate the triclinic reference box , whose replication generates the whole infinite latticeof stacked boxes /2 or g = 0. It is convenient to choosethe primitive vectors with the same handedness as the Cartesian referenceframe, in which case b1·(b2 × b3) is positive for aright-handed frame and negative for a left-handed one; the absolutevalue of this triple product is the volume of the triclinic box.13A triclinic lattice is fully definedby a set of three linearly independent vectors primitive unit cells, whose shape is largelyarbitrary (including non-convex shapes), and even a triclinic shapeis non-unique due to the infinitely many ways of selecting a validset of primitive vectors.12 Therefore, primitivevectors should be chosen in a sensible way, avoiding unnecessarilyskewed or elongated reference boxes that may fail to encompass themolecular complex of interest; sensible choices are available forthe usual regular parallelohedra . In some cases, though, itmay be impossible to keep the whole complex inside a reference boxthat is otherwise convenient for the system being analyzed . When dealing with PBCs, it is convenient to adopt a set of scaled coordinates  that can simplify many calculations and geometric transformations.A position vector r is related to the vector s of its scaled coordinates as13g is the geometric centerof the reference box and B is the box matrix obtained by collecting the primitive vectors as column matricesB is equalto b1·(b2 × b3), whose absolute value is, as noted above, thebox volume. Therefore, B has a non-null determinant andis thus invertible, givingrAB pointingfrom point A to point B, we getsAB = B–1rAB, where we defined sAB = sB – sA; thus, g is droppedwhen mapping free vectors.A point in physicalthree-dimensional space is usually written as a position vector andexpressed in terms of Cartesian coordinates, a, ⌈a⌋ = ⌊a + 1/2⌋, where ⌊·⌋denotes the floor function,15 and its vectorialcounterpart a = . If we consider an atom i at ri, with scaled position si = f–1(ri), it is easy to seethat atom i is inside a box that is ⌈si,α⌋ boxes awayfrom the reference box in each of the directions α = x, y, z and that the “local”position of that point in its box is identical to that of the pointsi =  gives ⌈si⌋ = and si° = . Similarly,if sij = sj – si is the vector between atoms i and j, the MI vector between them isi and j are too far apart; see below). The counterparts in the physicaltriclinic lattice can then be obtained by using 13 Therelations , which 1 of ref 2.3.B contains the actual lengthvalues of the primitive vectors , this cubiclattice is dimensionless, with s =  being atriplet of bare real numbers, where the subscripts x, y, and z refer to the cubic latticeaxes and not to the original ones in physical space. The mappings f and f–1 are affinetransformations, which preserve the following geometric features:17 linearity and planarity, parallelism and intersectionof lines and planes, and ratios of lengths between parallel line segments.As shown below, many transformations involving a triclinic latticecan be entirely conducted in the scaled cubic lattice, with the back-mappingtaking place only at the end.Thechange from physical Cartesian coordinates to scaled ones correspondsto a geometric transformation that maps the physical triclinic latticeto a non-physical lattice of unit cubes , with the original reference box being mapped to the cubecentered at the origin. Since 2.3M and N as RMN in physical spaceand as SMN in scaled space,we want to have RMN = BSMN so that we may use an equationanalogous to  The calculation of the RMN than RMN = BSMN. We note alsothat ∥RMN∥is a measure of molecular proximity but not necessarilya metric (in the sense used in topology18); for example, the triangle inequality ∥r̆MN∥ ≤ ∥r̆MP∥ + ∥r̆PN∥ may not hold for some molecules M, N, and P.Another candidate for KM for each molecule k ∈ M and l ∈ N arethe minimum-distance atoms defined in SMN as There is usuallya set of molecules that we identify as composing the molecular complexthat we want to assemble. The second step of the algorithm consistsin moving those molecules to new positions that, together, preservethe wholeness of that complex. This will generally imply translatingeach molecule by a different displacement that corresponds to an integernumber of boxes in each lattice direction. If we denote as M and N in RMN′ = RMNMI. Using SMN⌋ = ⌈SMP⌋ + ⌈SPN⌋, which is generally impossible:for example, SM = , SP = , and SN =  give ⌈SMN⌋ =  but ⌈SMP⌋ + ⌈SPN⌋ = . Therefore, werequire instead that KM of each added molecule M from the KN of a previously assembled neighboringmolecule N. More exactly, the assembled complex isbuilt from its initially non-assembled molecules using the followingsequential procedure:(a)KP = 0 and mark P as assembledSelect an initial molecule (b)RMNMI∥, where M is unmarked and N is marked as assembled and thencompute KM with M as assembled;Select the pair of moleculeswiththe lowest ∥(c)Repeatstep (b) until all moleculesin (d)si′ = si.Apply This will produce a complex having its molecules assembledby MI pairwise proximity, thus producing a tree (in the graph-theoreticsense19) that is independent of the initiallychosen molecule. However, this assembled tree will be in general notcentered nor fully contained in the reference box, possibly overlappingseveral of its neighboring boxes. In particular, if the molecularcomplex includes intrinsically periodic parts composed of small molecules, its molecules tend to get scattered overa substantially large region, possibly larger than a single box . Therefore,we define the vectors smin′ and smax′ withcomponentsFor greater flexibility, it is convenient thatdifferent partsof the system may be used for centering along different directions:for example, for a protein embedded in a horizontally oriented lipidbilayer, we typically want to use only the protein for the horizontalcentering  and use the whole complex for the vertical centering.Thus, instead of using a single set i, itsposition si″ obtained from step 3 could betranslated to the new positionM, computed as in Asnoted above, when the molecular complex includes intrinsically periodicparts composed of small molecules , step 3may end up with some of those molecules totally or partially outsideof the reference box. Furthermore, some non-assembled molecules thatwere initially inside the reference box may now be outside due to the translation performed in step 3. Therefore,it is necessary to move those outside molecules into the referencebox by translating them an integer number of boxes in each direction,which is the final step of the algorithm. A simple way of doing thisis to move each molecule so that its center is placed inside the referencebox; molecules partially outside will remain partially outside, buttheir external portion will be minimized. Therefore, we can apply x, y, z:However, in some cases, this final mapping into the reference boxmay not be convenient along some directions: for example, if a horizontallyoriented lipid bilayer experiences undulations large enough to makeits vertical range (slightly) higher than the box vertical size, wewill most likely want to move the outside lipid molecules into thereference box only along the two horizontal directions but not alongthe vertical one because that would cut some undulation crests 7. In facapplying  to all a2.4ri}, together with the primitive vectors of the corresponding triclinic reference box. Thiscan be a molecular structure file in some standard format . It is assumedthat the provided coordinates correspond to whole molecules , though these are not required to be totallyor even partially encompassed by the triclinic reference box.An initial set of atomic coordinates, {i belong to each molecule M. Since only the sets of atoms per molecule are needed, the algorithmdoes not need a full molecular topology, which makes it more general.The specification of the molecules, thatis, of whichatoms The specification of the sets of moleculesto be hierarchicallyassembled: Thespecification of the sets of molecules to be centeredalong each direction: The specificationof the sets of molecules that shouldbe PBC-mapped into the reference box along each direction: The algorithm then performs the steps 1–4 described,resulting in the consecutive transformations {ri} → {si} → {si′} → {si″} → {si‴} → {ri‴}. The final atomic coordinates, {ri‴}, can then be saved in a new molecularstructure file, keeping the original box vectors . Given theabove description, the algorithm FixBox requires the following input:gro file5 withthe atomic coordinates and primitive vectors plus a definitionsfile with all other required information and writes as outputa gro file with the system fixed in the referencebox; the input gro file may contain multipleconfiguration snapshots whose fixed counterparts are written to theoutput file. The definitions file is a very simple text file thatis parsed on a single-line basis: a line starting with G is a group definition followed by single-line definitionsof its elements, which may be molecules defined through atom ranges(line starting with a), single-residue moleculesdefined through the residue name (line starting with n), or previously defined groups (line starting with g); a line starting with A specifies the groupto be used in an assembly stage, with successive such lines correspondingto C specifies the groups to be used for P specifies the groupsto be used for Proteins contains the three proteins , Bilayer contains allthe blue molecules (assumed to consist each of a single residue namedBLU), and System contains the whole molecularsystem. As shown in A Proteins), and then the bilayer is assembled on top of them (with A Bilayer). The proteins are then used for centeringalong the x- and y-axes and thewhole system for centering along the z-axis. Thefinal three flags on that line indicate what happens if either ofthe x, y, z); in this case, an error (E) occurs if the proteins extend beyond the xy-planeand a warning (W) is issued if the system extendsbeyond the z-axis . Finally, bilayer molecules are moved into the referencebox along the x- and y-axes butnot along the z-axis , which is indicated with the None group. There are usually alternative ways to define groups, assembly,centering, and PBCs that lead to the same final result; the user shouldchoose the definitions that seem more intuitive or convenient in eachcase.FixBox is currently implemented as a C programthat reads as inputa 3This section illustratesthe use of the FixBox algorithm with problematicconfigurations of various types of systems, showing the results aftereach translation step of the algorithm . Theintermolecular distance 20 This is a simple case consisting of a two-chainprotein and water molecules, and a definitions file is shown in W flags for the centeringalong all directions. The triclinic box of this system is equivalentto a rhombic dodecahedron and, if necessary, the final arrangementcan be transformed to that geometry using a suitable tool ; but thatmay not be needed, as when the configuration is stripped of waterand subjected to a Poisson–Boltzmann calculation.20sn-glycero-3-phosphocholine (DMPC) membrane bilayer in water.21 As shown in xy-plane. Wenote that the assembly step results in an almost complete separationof the two monolayers because, as already noted in E are used for the centering on the xy-plane since a failure to encompass the peptide means that it unfolded(and a wider box should have been used), while a warning flag W is used for the centering along the z-axis in order to detect dissociation of the peptide from the membrane.c oxidase molecules (subunitsI and II) embedded on a DMPC bilayer that displays substantial undulations.As seen in xy-plane is done witha group consisting of a single cytochrome c oxidase(FirstProtein), while the set of all proteinsand lipids is used to center along the z-axis; inthis case, warning flags (W) were used alongall directions .No molecules are moved into the reference box along the z-axis to avoid cutting the undulation crests, which are indeed presentin the configuration being shown. The strategy adopted for centeringon the xy-plane is arguable, opting for splittingagain a “molecular complex” that, instead of forminga single aggregate, displays several small ones. The alternative tocenter the whole Protein group on the xy-plane would result in a bounding box much wider thanthe reference box, which, unlike the situation along the z-axis, would not be a satisfactory solution. This illustrates thatFixBox is at present sub-optimal when dealing with multiple aggregates.A more challenging membrane system is shown in The fact that FixBox does not make direct useof a topology canalso be occasionally exploited. For example, if a molecular complexcontains a strictly periodic (“infinite”) molecule,the algorithm can be easily misled to do what we want by treatingits structural units as distinct molecules, which, in analogy witha lipid bilayer, would then be assembled in a proper configurationthat preserves the strict molecular periodicity.424 or some constant-pH MD methods4). The use of a unified triclinic framework makes the algorithm agnosticwith respect to box geometry (only the box primitive vectors mustbe provided in addition to the atomic coordinates), and the fixingof the system is based on a simple set of definitions of its assemblingparts and their intended arrangement (provided in a definitions file).FixBox is intended for general use as illustrated in The FixBox algorithmpresented here provides a general and easy-to-usemethod to fix a molecular system that has been “broken”during a simulation with PBCs. Its new features include multi-stagereassembly of a molecular complex based on the shortest distance betweenits molecules, centering along different directions using differentsets of molecules, centering using bounding boxes, and PBC-wrappingalong different directions using different sets of molecules; together,these allow for a level of “box fixing” not usuallyattainable with available tools. FixBox can be used to process simulationtrajectories prior to analysis or as part of a more complex automatedprocedure in which box fixing is required (e.g., web servers for Poisson–Boltzmanncalculations5https://www.itqb.unl.pt/simulation/in-house-software, both standalone and as part of our in-house implementation of thestochastic titration method for constant-pH MD,4 whichwas the main drive for its development.Thecurrent open source implementation of FixBox is available at


The aim of this hermeneutic-phenomenological study was to explore the perspectives of 12 patients, 17 nurses, and 4 musicians on patient-tailored live music interventions in a hemodialysis setting. Twenty-six semi-structured interviews were collected—17 with patients, 9 with nurses. Furthermore, 18 moderate participation observations, whilst 1 semi-structured group interview with 3 nurses and 3 musicians, and 13 reflective journals from musicians were collected. Within the analysis—based on Ricoeur’s theory of interpretation—two overall themes emerged: (1) the inner space and (2) the participating space, followed by five subthemes: (1a) Entering a calm and enjoyable pause bubble; (1b) Resting in a thought-free state of mind; (1c) Traveling in the past and catching the moment through heartfelt music; (2a) Bringing positive changes into life; (2b) The artistic quality mediating a magnificent and beautiful experience. We found that patient-tailored live music was a meaningful break, influencing mental and physical well-being, time perception, community, work environment, and artistic approach. The artistic quality of the music was essential—together with the musicians’ social awareness, empathy, and ability to interact with the patients—in creating meaningful moments for patients and staff. Overall, the music interventions were a welcome change in a predictable world of stressful routines and repetitive treatments. For decades, music-based interventions have been used in different healthcare settings. A recent report published by the World Health Organization identified over 3000 studies showing a major role for the arts in the prevention of ill health, promotion of health, and management and treatment of illness throughout life . Howevern = 1731)  have been here, I think it’s nice, because then suddenly 20 min and a half hour or so has passed by. Without really noticing it. So, it’s nice that it [the musical experience] makes time go faster, in a way.” (IP5).By actively choosing to take a break from work, several nurses felt an impact on their pulse rate and that they could catch their breath. It seemed that going into an inner space helped them let go of stress and work pressure: “Then I chose to prioritize being al-lowed to sit and enjoy it, half the time, I did not have to work at the same time. Well, it’s simply, you... your heart rate goes all the way down and you just get your head emptied and that gives such a break.” (IN10). However, some nurses experienced a tension between being at work and being responsible for the patients and at the same time devoting their attention to the music. They found it distracting and worried that they might overlook important signals from the patients, with serious consequences. One nurse described it in the following way: “As a nurse, you cannot completely indulge in the music because you sit and watch the machines and patients.” (IN17), whereas others stated that they were able to accommodate both the musical experience and their work during the limited 30 min period when the music was played.The musical repertoire was carefully selected, with a mix of well-known pieces in different tempos, styles, and arrangements, and less familiar pieces that were suitable for the setting, taking into account musical structure, harmony, length, and complexity vs. simplicity. To meet the patients´ preferences and situations, different musical expressions were chosen, including romantic, quiet, beautiful, calming, subdued, sad, and happy music: “In this setting, I think that a mix of very subdued, beautiful, romantic, happy, and sad music is appropriate.” (GM3).The musicians underlined the importance of performing music that they loved and were closely associated with: “The music had to be chosen and played with your heart.” (RJ1).One of the musicians described it in the following way: “Music is more than just satisfying people. Music should also be used to tease people’s curiosity, enabling openness to something new, I think. So, there are more elements to it.” (GM3).When the musicians performed well-known pieces, it prompted positive memories: “like traveling in the past,” as one patient noted (IP1), whereas unfamiliar classical guitar pieces brought to mind soothing atmospheres and images of the sea and calming waves: “When it was so quiet and so calm, I thought of the sea. The waves that came rushing just as quietly and so calm, that is. You can imagine some pictures.” (IP11).Beyond the repertoire, it seemed that the patients´ and staff’s experiences of the music depended on the musician’s presentation and the music’s intensity. One patient highlighted the connection between the quality of the listening experience and how the music was introduced: “I had a bit of dialogue with him. We talked a little bit about it. I think that´s good. At least a change from everyday life here.” (IP7). When the guitar duo decided to play unfamiliar pieces, they made an effort to introduce the music by telling personal anecdotes to create imagery that would help the patients immerse themselves more easily in the music. In contrast, a solo female classical guitarist performed in a constant musical flow which she did not break with verbal communication. Slow, calming, and soothing music made the patients close their eyes and dream away. When the music was performed rhythmically in an energized, up-tempo, and lively way, it encouraged the patients and staff to move: “It gives me either energy or peace.” (IN13). Even though they were not dancers, and they did not describe their activity as dancing, the rhythm made them feel like moving. Patients described it in the following way: “If it´s up-tempo, then you go into it.” (IP11); “Something spontaneous just happens... It’s not the same as dancing. I’m not such a big dancer. But something happens with that rhythm. I feel like moving to the beat of the music.” (IP7).The semi-structured interviews with the nurses revealed that experiencing the music encouraged the patients to show other sides of themselves, for instance, talking about a family member who was a musician or their own love of a particular Danish composer. Possibly, the music interventions created new connections between the nurses and patients, enabling the nurses to better see the person rather than just the patient, and to direct the conversation towards new shared and positive experiences in the clinic. Furthermore, one patient expressed sympathy and understanding for the staff’s work situation and highlighted the potential benefits of the music for the staff: “It must be a nice change in their lives, with all the mechanics [HD equipment]. With all that they must do [for patients on HD], that must be really nice.” (IP10).One of the musicians noted that music might act as a “breathing space giving the nurses new energy when they felt sorry for their patients and powerless to be able to improve their situation through their nursing”. This was supported by a nurse saying that the music interventions made her happy and professionally proud when she noticed how the initiative benefitted this group of patients. Another nurse stated that the music provided a special, encouraging, and life-affirming moment for one male patient, encouraging him to go on with life: “It was really meaningful. Through this experience, he will be able to cope for another day.” (GN17). One musician pointed out that, in addition to the musical experience itself, the per-former’s approach can be a meaningful catalyst for new ways of caring and communication, creating new communities and transforming people’s lives in the hospital environment: “In fact, the musicians and the music can bring something new. It can open up life [for new perspectives] to come and enable people to start talking to each other and commenting a little, and you [the nurse] get a little change from everyday triviality.” (GM3). Another described the treatment room as an intimate space where the musician was close to the patients and, e.g., felt a very close and present contact with a male patient, as if both were sharing the musical moment and performing together: “When patients spontaneously said, “It’s nice to have something positive to think about” and “It’s a great atmosphere you can create with your guitar,” it brought a feeling of togetherness into the room.” (GM1).When the patients’ behavior suggested detachment, e.g., eyes closed or watching television, this made the task more complex for the musicians (RJ4). However, as the musicians performed repeatedly for the same group of patients over the project period, better mutual contact developed between some of these patients and the musicians (RJ1). At one of the final music interventions, a patient requested his favorite song (IP7), and the patients in the room sang along together with the musician. The musician noted that this was a very special and life-affirming moment.For patients and nurses, the music was a shared experience that gave rise to feelings of joy, cohesion, openness, and community. It was a happy experience that they could talk about afterwards: “So what I experience is that the music creates calmness, cohesion, and community. And that is something we can use to build upon. For all the other times [HD treatments]. And that’s what I’ve been thinking here: that it’s really nice.” (IN1). The nurses emphasized that the music made a positive difference to their workday and that there was a positive and expectant mood among patients and staff in the morning before the musicians arrived. The musicians noted that, when they entered the treatment rooms, they also felt that the patients were looking forward to the music. One patient commented: “It´s nice to be together with people who express joy in music.” (IP7). In addition, the music may balance and dissolve the divisions between the roles of patients and staff, thereby creating a new and deeper mutual understanding. This point was supported by a nurse: “We work in a unit where it is necessary that you can also show yourself as a person to the patients.” (IN1).Many nurses and patients described the musicians’ presence, talent, personality, and approach as central to their experience of and engagement with the intervention. The nurses were impressed by the musicians, their professionalism, and their way of being present and adaptive in the treatment rooms: “It´s a great gift and an opportunity to have real musicians here who play live music, and who perform so nicely and beautifully.” (IN5). One noted that the musicians were very attentive and humble, unaffected by the alarms of the machines: “They are extremely attentive. Really. Probably also because they are so musical and therefore creative and very sensitive people.” (IN10). The patients were also impressed by the musicians´ artistic level, and some mentioned that seeing how the musicians performed was a positive and reflective experience: “It’s nice when you look at the musicians, how they are active and such. And it gives you something. Then you can follow what they do and such. There is a lot of hard work behind it.” (IP11).The musicians experienced the staff as friendly, accommodating, and supportive: “The staff at the HD department were very welcoming and committed, and I think it was a very professional and a satisfying experience.” (GM1). The nurses’ commitment to being open-minded and engaged with the live music performances in the treatment rooms had a huge impact on the musicians. They felt that the nurses’ professional approach created a safe and stable environment, which helped in situations, for instance, when patients lay with eyes closed, making them difficult to read (GM2). Sometimes, the nurses gave the musicians appreciative looks and commented on the music, and it seemed that the musicians saw the nurses both as a link to the patients and as part of the audience in the same way as the patients: “But there was something that I thought was really cool. Not just to play for the patients, but also to play for you [nurses] who were in the treatment rooms.” (GM3).Meeting patients on their own terms and adapting to their state of mind required a sensitive, intuitive, and empathetic approach. While the musicians’ attention was directed outward, they had to accentuate the calm nuances of the music rather than “filling the space” as they would in the familiar environment of a concert hall. The musicians matched the intensity of the music to the state of mind and energy levels of the patients in the treatment rooms; therefore, they sometimes changed the tempo or even the order of the repertoire according to the patients’ feedback. The musicians created a safe and positive space, inviting the patients to participate by asking questions, commenting, saying what they experienced during the music, and bringing memories to life. One musician described it in the following way: “That way, the patient becomes more active and is invited to join in and as a natural consequence I think that the patient will listen more deeply and differently to what is played on the guitar.” (GM1). If the patients were passively listening, for instance with eyes closed, the musicians noted that they would play more tenderly, dreamily, and quietly. In contrast, they would choose to play accessible, energetic, and upbeat music for attentive patients who were seeking contact. One musician felt that this intuitive and adaptive approach had implications for the musicians’ professional and personal development: “Participating in this space is like a development springboard both as a musician and as a human being.” (GM3). Experiencing the diversity of the patients’ respective personalities and reactions in this intimate space meant the musicians had to be open, artistically aware, and prepared for the unpredictable.Our data show that patient-tailored live music performed by professional musicians creates both an inner space and a participating space—a musical break. This musical break, alone or with others, represents a respite from the HD treatment—a temporary diversion from the burdensome treatment and stressful work environment, allowing patients’ and nurses’ thoughts to run free and create new perspectives. We found that patient-tailored live music interventions fostered well-being among patients undergoing HD, improved patient–nurse relationships and relaxation among nurses, and created a new artistic and social awareness for the professional musicians entering this healthcare environment. The themes identified showed that the music interventions were a meaningful break that influenced mental and physical well-being, time perception, community, professional attitudes, and artistic approach. The artistic quality of the music was essential, together with the musicians’ social awareness, empathy, and ability to interact with the patients, in creating meaningful moments for patients and staff. Overall, the music interventions were a welcome and positive change in a predictable world of stressful routines and repetitive treatments.For some, the music created a mutual consciousness, sensitivity, and attunement between patients, nurses, and musicians. It seemed that a third common space arose—a “we”—a resonant space of reaching out and letting go of negative thoughts, regardless of one’s role as a patient or nurse. It is possible that the music created an autonomous space—an “intermediate world” away from the medical hierarchy—as well as a sound environment, where patients, staff, and musicians could connect and communicate, without words, through music . AccordiOur findings are in line with Heidegger’s theories that being in the world is a predictor for being within the world and the existence of an understanding of the presence of others . HeideggThe strategy of combining well-known music with unfamiliar music aimed to pique the patients’ curiosity and also open them up to new perspectives on the music they already knew. The music intervention created an inner space where patients could experience memories from their past. Throughout life, many people build up an individual soundtrack—a musical memory lane—consisting of specific genres or pieces of music related to meaningful life events ,43,44,45According to Ruud, we construct ourselves when we listen to music . Music eThis self-construct might also counteract feelings of burnout among nurses in the HD setting, on both a personal and professional level. It is potentially a way to manage a stressful work environment, as well as creating shared experiences and pathways of communication with the patients. Our results are in line with Carswell et al., showing that individual art-based interventions improve well-being among nurses working in an HD unit ,50.Another key finding is that patients and nurses felt that the artistic quality of the music was important to the experience. These findings resemble those of Smilde, arguing that “authenticity of sound,” “fitness for purpose,” and “relevance to context” are important elements in achieving quality, and therefore meaningfulness, when involving music in healthcare contexts . In thisThis study was part of a randomized controlled pilot trial and aimed to garner an in-depth understanding of the patient, staff, and musician perspectives. One limitation of this study may be that the primary investigator had the roles of both selecting and supervising the musicians, as well as analyzing the data, including the reflective journals. This might have influenced the perspectives and reflections on the data. On the other hand, a strength of the analysis was that the second and last co-authors also participated in the in-depth analysis and brought different perspectives and reflections to the analysis and discussion of the findings. The study took place on a single site; thus, multiple sites might discover further perspectives. Another limitation could be that the positive feedback from the patients and nurses might be explained by novelty bias, why implementing patient-tailored live music into clinical practice maybe will show some other findings.A major strength of this study was the overall sample size with 18 moderate participation observations, 17 semi-structured interviews with patients, 9 semi-structured interviews with nurses, 1 semi-structured group interview, and 13 reflective journals from the musicians. These provide strong data material seen from a phenomenological-hermeneutical perspective. Furthermore, the various methods used to gather data are also a strength when bringing forth various perspectives to the phenomenon “patient-tailored live music intervention” ,34.We found that patient-tailored live music performed by professional musicians had positive effects on mental and physical well-being, time perception, and community among patients undergoing the burdensome treatment of HD. For the nurses, the music was relaxing and de-stressing, and had a positive effect on their work by improving their patient relationships and compassion. For the professional musicians, their artistic and social awareness was enhanced when they entered the HD setting. The artistic quality of the music was essential—together with the musicians’ social awareness, empathy, and ability to interact with the patients—in creating meaningful moments for the patients and staff.