Clinical implications

Funding: GC was funded by Fundaçao para a Ciência e Tecnologia (FCT; Portugal) through a PhD Scholarship (SFRH/BD/130210/2017). AJOM was funded by FCT (Portugal) through a Junior Research and Career Development Award from the Harvard Medical School e Portugal Program (HMSP-ICJ/0020/2011). GC and AJO-M were supported by grant PTDC/MED-NEU/31331/2017, and AJO-M by grant PTDC/MED-NEU/30302/2017, funded by national funds from FCT/MCTES and co-funded by FEDER, under the Partnership Agreement Lisboa 2020 - Programa Operacional Regional de Lisboa. The content of this study is solely the responsibility of the authors and does not necessarily represent the official views of the Fundaçao para a Ciência e Tecnologia, Harvard University or its affiliated academic health care centers. AJO-M was national coordinator for Portugal of a noninterventional study (EDMS-ERI-143085581, 4.0) to characterize a Treatment-Resistant Depression Cohort in Europe, sponsored by Janssen-Cilag, Ltd (2019e2020), is recipient of a grant from Schuhfried GmBH for norming and validation of cognitive tests, and is national coordinator for Portugal of trials of psilocybin therapy for treatment-resistant depression, sponsored by Compass Pathways, Ltd (EudraCT number 2017-003288-36 and 2020-001348- 25), and of esketamine for treatment-resistant depression, sponsored by Janssen-Cilag, Ltd (EudraCT NUMBER: 2019-002992-33). AP-L is a co-founder of Linus Health and TI Solutions AG; serves on the scientific advisory boards for Starlab Neuroscience, Neuroelectrics, Magstim Inc., Nexstim, Cognito, and MedRhythms; and is listed as an inventor on several issued and pending patents on the real-time integration of noninvasive brain stimulation with electroencephalography and magnetic resonance imaging. None of the aforementioned agencies had a role in the design and conduct of the study, in the collection, management, analysis, and interpretation of the data, in the preparation, review, or approval of the manuscript, nor in the decision to submit the manuscript for publication. The remaining authors have declared that they have no potential conflicts of interest involving this work, including relevant financial activities outside the submitted work and any other relationships or activities that readers could perceive to have influenced, or that give the appearance of potentially influencing what is written.Background: When repetitive transcranial magnetic stimulation (rTMS) is used to treat medication refractory depression, the treatment pulse intensity is individualized according to motor threshold (MT). This measure is often acquired only on the first day of treatment, as per the protocol currently approved by Food and Drug Administration. Objective: Here, we aimed to assess daily MT variability across an rTMS treatment course and simulate the effects of different schedules of MT assessment on treatment intensity. Methods: We conducted a naturalistic retrospective study with 374 patients from a therapeutic rTMS program for depression that measures MT daily. Results: For each patient, in almost half the TMS sessions, MT varied on average more than 5% as compared to the baseline MT acquired in the first treatment day. Such variability was only minimally impacted by having different TMS technicians acquiring MT in different days. In a smaller cohort of healthy individuals, we confirmed that the motor hotspot localization method, a critical step for accurate MT assessment, was stable in different days, arguing that daily MT variability reflects physiological variability, rather than an artifact of measurement error. Finally, in simulations of the effect of one-time MT measurement, we found that half of sessions would have been 5% or more above or below target intensity, with almost 5% of sessions 25% above target intensity. The simulated effects of weekly MT measurements were significantly improved. Conclusions: In conclusion, MT varies significantly across days, not fully dependent on methods of MT acquisition. This finding may have important implications for therapeutic rTMS practice regarding safety and suggests that regular MT assessments, daily or at least weekly, would ameliorate the effect.publishersversionpublishe

Variability in motor threshold

Funding Information: GC was funded by Funda??o para a Ci?ncia e Tecnologia (FCT; Portugal) through a PhD Scholarship (SFRH/BD/130210/2017). AJO-M was funded by FCT (Portugal) through a Junior Research and Career Development Award from the Harvard Medical School ? Portugal Program (HMSP-ICJ/0020/2011). GC and AJO-M were supported by grant PTDC/MED-NEU/31331/2017, and AJO-M by grant PTDC/MED-NEU/30302/2017, funded by national funds from FCT/MCTES and co-funded by FEDER, under the Partnership Agreement Lisboa 2020 - Programa Operacional Regional de Lisboa. The content of this study is solely the responsibility of the authors and does not necessarily represent the official views of the Funda??o para a Ci?ncia e Tecnologia, Harvard University or its affiliated academic health care centers. Funding Information: GC was funded by Fundação para a Ciência e Tecnologia (FCT; Portugal) through a PhD Scholarship ( SFRH/BD/130210/2017 ). AJO-M was funded by FCT (Portugal) through a Junior Research and Career Development Award from the Harvard Medical School – Portugal Program ( HMSP-ICJ/0020/2011 ). GC and AJO-M were supported by grant PTDC/MED-NEU/31331/2017, and AJO-M by grant PTDC/MED-NEU/30302/2017, funded by national funds from FCT/MCTES and co-funded by FEDER , under the Partnership Agreement Lisboa 2020 - Programa Operacional Regional de Lisboa. The content of this study is solely the responsibility of the authors and does not necessarily represent the official views of the Fundação para a Ciência e Tecnologia, Harvard University or its affiliated academic health care centers. Funding Information: AJO-M was national coordinator for Portugal of a non-interventional study (EDMS-ERI-143085581, 4.0) to characterize a Treatment-Resistant Depression Cohort in Europe, sponsored by Janssen-Cilag, Ltd (2019–2020), is recipient of a grant from Schuhfried GmBH for norming and validation of cognitive tests, and is national coordinator for Portugal of trials of psilocybin therapy for treatment-resistant depression, sponsored by Compass Pathways, Ltd (EudraCT number 2017-003288-36 and 2020-001348-25), and of esketamine for treatment-resistant depression, sponsored by Janssen-Cilag, Ltd (EudraCT NUMBER: 2019-002992-33). AP-L is a co-founder of Linus Health and TI Solutions AG; serves on the scientific advisory boards for Starlab Neuroscience, Magstim Inc., Radiant Hearts, and MedRhythms; and is listed as an inventor on several issued and pending patents on the real-time integration of noninvasive brain stimulation with electroencephalography and magnetic resonance imaging. None of the aforementioned agencies or companies had a role in the design and conduct of the study, in the collection, management, analysis, and interpretation of the data, in the preparation, review, or approval of the manuscript, nor in the decision to submit the manuscript for publication. The remaining authors have declared that they have no potential conflicts of interest involving this work, including relevant financial activities outside the submitted work and any other relationships or activities that readers could perceive to have influenced, or that give the appearance of potentially influencing what is written.publishersversionpublishe

Recommending Physical Activity to Your Aging Patients? What Clinicians Need to Know to Increase Adherence From the Older Adult Perspective

A wealth of scientific evidence supports that being physically active may prevent or delay the onset of cognitive impairment and dementia. However, a critical barrier is that while most clinicians recommend physical activity (PA) and older adults recognize its health benefits, most older adults fail to regularly practice PA. Thus, it is necessary to explore and disseminate knowledge on how to help clinicians truly partner with people and help them to change their behavior and become more active. Clinical and scientific efforts are underway to establish dose-specific PA recommendations for cognitive brain health. However, an important knowledge gap is how to develop effective strategies to increase PA adherence in aging. To better understand the perspective of older adults, we undertook a mixed-method study on sixty-five sedentary older adults at risk for cognitive decline. Participants answered a questionnaire battery related to PA engagement, and a subcohort participated in a remote focus group. Our findings revealed four main themes: First, age and aging are determinants in PA practice. Second, maintaining both an active mind and autonomy are priorities, but planned PA is not usually related as part of being “active.” Third, motivational challenges in PA engagement were noted. And fourth, they emphasized a call for tailored recommendations. Therefore, we present a multidimensional model of PA adherence to maximize brain health in older adults and suggest a tool kit and key questions to effectively screen sedentary aging adults and translate current guidelines into the needs of the individual by using behavior change strategies

Three years of the coronavirus disease 2019 pandemic in a european region: a population-based longitudinal assessment in Madrid between 2020 and 2022

Our objective was to assess the health impact of coronavirus disease 2019 (COVID-19) during 2020-2022 in the Madrid region. We included all individuals registered in the Madrid Health System Registry as of 31 December 2019, and followed them until 31 December 2022. Using a unique personal identifier, we linked the databases of primary care, hospitals, pharmacies, certified laboratories performing diagnostic tests, vaccines, and mortality. Of 6 833 423 individuals, 21.4% had a confirmed COVID-19 diagnosis, and 1.5% had a COVID-19 hospitalization (primary diagnosis). Thirty-day mortality was 1.6% for confirmed COVID-19 (from 11.4% in first semester 2020 to 0.4% in first semester 2022). Thirty-day mortality was 10.8% for COVID-19 hospitalizations (from 14.0% in first semester 2020 to 6.0% in second semester 2022). There were 24 073 deaths within 30 days of a confirmed COVID-19 diagnosis. Advanced age, male sex, higher socioeconomic deprivation, and comorbidities were associated with higher mortality. By linking administrative and clinical databases, we characterized the burden of the COVID-19 pandemic in Madrid over 3 years. Our analysis proposes a high-level framework for comparisons of the burden of COVID-19 across areas worldwid

New Results from the Cryogenic Dark Matter Search Experiment

Using improved Ge and Si detectors, better neutron shielding, and increased counting time, the Cryogenic Dark Matter Search (CDMS) experiment has obtained stricter limits on the cross section of weakly interacting massive particles (WIMPs) elastically scattering from nuclei. Increased discrimination against electromagnetic backgrounds and reduction of neutron flux confirm WIMP-candidate events previously detected by CDMS were consistent with neutrons and give limits on spin-independent WIMP interactions which are >2X lower than previous CDMS results for high WIMP mass, and which exclude new parameter space for WIMPs with mass between 8-20 GeV/c^2.Comment: 4 pages, 4 figure

The Brazilian Developments on the Regional Atmospheric Modeling System (BRAMS 5.2): An Integrated Environmental Model Tuned for Tropical Areas

We present a new version of the Brazilian developments on the Regional Atmospheric Modeling System where different previous versions for weather, chemistry and carbon cycle were unified in a single integrated software system. The new version also has a new set of state-of-the-art physical parameterizations and greater computational parallel and memory usage efficiency. Together with the description of the main features are examples of the quality of the transport scheme for scalars, radiative fluxes on surface and model simulation of rainfall systems over South America in different spatial resolutions using a scale-aware convective parameterization. Besides, the simulation of the diurnal cycle of the convection and carbon dioxide concentration over the Amazon Basin, as well as carbon dioxide fluxes from biogenic processes over a large portion of South America are shown. Atmospheric chemistry examples present model performance in simulating near-surface carbon monoxide and ozone in Amazon Basin and Rio de Janeiro megacity. For tracer transport and dispersion, it is demonstrated the model capabilities to simulate the volcanic ash 3-d redistribution associated with the eruption of a Chilean volcano. Then, the gain of computational efficiency is described with some details. BRAMS has been applied for research and operational forecasting mainly in South America. Model results from the operational weather forecast of BRAMS on 5 km grid spacing in the Center for Weather Forecasting and Climate Studies, INPE/Brazil, since 2013 are used to quantify the model skill of near surface variables and rainfall. The scores show the reliability of BRAMS for the tropical and subtropical areas of South America. Requirements for keeping this modeling system competitive regarding on its functionalities and skills are discussed. At last, we highlight the relevant contribution of this work on the building up of a South American community of model developers

Rarity of monodominance in hyperdiverse Amazonian forests.

Tropical forests are known for their high diversity. Yet, forest patches do occur in the tropics where a single tree species is dominant. Such "monodominant" forests are known from all of the main tropical regions. For Amazonia, we sampled the occurrence of monodominance in a massive, basin-wide database of forest-inventory plots from the Amazon Tree Diversity Network (ATDN). Utilizing a simple defining metric of at least half of the trees ≥ 10 cm diameter belonging to one species, we found only a few occurrences of monodominance in Amazonia, and the phenomenon was not significantly linked to previously hypothesized life history traits such wood density, seed mass, ectomycorrhizal associations, or Rhizobium nodulation. In our analysis, coppicing (the formation of sprouts at the base of the tree or on roots) was the only trait significantly linked to monodominance. While at specific locales coppicing or ectomycorrhizal associations may confer a considerable advantage to a tree species and lead to its monodominance, very few species have these traits. Mining of the ATDN dataset suggests that monodominance is quite rare in Amazonia, and may be linked primarily to edaphic factors

The Brazilian developments on the Regional Atmospheric Modeling System (BRAMS 5.2): an integrated environmental model tuned for tropical areas

We present a new version of the Brazilian developments on the Regional Atmospheric Modeling System (BRAMS), in which different previous versions for weather, chemistry, and carbon cycle were unified in a single integrated modeling system software. This new version also has a new set of state-of-the-art physical parameterizations and greater computational parallel and memory usage efficiency. The description of the main model features includes several examples illustrating the quality of the transport scheme for scalars, radiative fluxes on surface, and model simulation of rainfall systems over South America at different spatial resolutions using a scale aware convective parameterization. Additionally, the simulation of the diurnal cycle of the convection and carbon dioxide concentration over the Amazon Basin, as well as carbon dioxide fluxes from biogenic processes over a large portion of South America, are shown. Atmospheric chemistry examples show the model performance in simulating near-surface carbon monoxide and ozone in the Amazon Basin and the megacity of Rio de Janeiro. For tracer transport and dispersion, the model capabilities to simulate the volcanic ash 3-D redistribution associated with the eruption of a Chilean volcano are demonstrated. The gain of computational efficiency is described in some detail. BRAMS has been applied for research and operational forecasting mainly in South America. Model results from the operational weather forecast of BRAMS on 5 km grid spacing in the Center for Weather Forecasting and Climate Studies, INPE/Brazil, since 2013 are used to quantify the model skill of near-surface variables and rainfall. The scores show the reliability of BRAMS for the tropical and subtropical areas of South America. Requirements for keeping this modeling system competitive regarding both its functionalities and skills are discussed. Finally, we highlight the relevant contribution of this work to building a South American community of model developers.CNPqFAPESPEarth System Research Laboratory at the National Oceanic and Atmospheric Administration (ESRL/NOAA), Boulder, USAInst Nacl Pesquisas Espaciais, Ctr Previsao Tempo & Estudos Climat, Cachoeira Paulista, SP, BrazilDiv Ciência da Computação, Instituto Tecnológico de Aeronáutica, São José dos Campos, SP, BrazilUniv Estadual Paulista Unesp, Fac Ciencias, Bauru, SP, BrazilCtr Meteorol Bauru IPMet, Bauru, SP, BrazilUniv Fed Sao Paulo, Dept Ciencias Ambientais, Diadema, SP, BrazilUniv Sao Paulo, Inst Astron Geofis & Ciencias Atmosfer, Sao Paulo, SP, BrazilUniv Fed Campina Grande, Dept Ciencias Atmosfer, Campina Grande, PB, BrazilEmbrapa Informat Agr, Campinas, SP, BrazilUniv Fed Sao Paulo, Inst Ciencia & Tecnol, Sao Jose Dos Campos, SP, BrazilUniv Fed Rio Grande do Norte, Dept Ciencias Atmosfer & Climat, Programa Pos Grad Ciencias Climat, Natal, RN, BrazilInst Nacl Pesquisas Espaciais, Ctr Ciencias Sistema, Sao Jose Dos Campos, SP, BrazilUniv Fed Sao Joao Del Rei, Dept Geociencias, Sao Joao Del Rei, MG, BrazilInst Nacl Pesquisas Espaciais, Lab Associado Computacao & Matemat Aplica, Sao Jose Dos Campos, BrazilUniv Evora, Inst Ciencias Agr & Ambientais Mediterr, Evora, PortugalUniv Lusofona Humanidades & Tecnol, Ctr Interdisciplinar Desenvolvimento Ambient Gest, Lisbon, PortugalUniv Fed Pelotas, Fac Meteorol, Pelotas, RS, BrazilUnive Tecnol Fed Parana, Londrina, PR, BrazilNASA, Goddard Space Flight Ctr, Univ Space Res Assoc, Goddard Earth Sci Technol & Res Global Modeling &, Greenbelt, MD USAUniv Fed Sao Paulo, Inst Ciencia & Tecnol, Sao Jose Dos Campos, SP, BrazilUniv Fed Sao Paulo, Inst Ciencia & Tecnol, Sao Jose Dos Campos, SP, BrazilCNPq: 306340/2011-9FAPESP: 2014/01563-1FAPESP: 2015/10206-0FAPESP: 2014/01564-8Web of Scienc