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openaire: EC/H2020/713645/EU//BioMEP Funding Information: We thank Drs. Kristian Donner, Greg Schwartz, Gabriel Peinado, and Christophe Ribelayga for valuable comments on the manuscript; Matthew Dunkerley and Sathish Narayanan for the design of the data acquisition software; Dr. Martta Viljanen for technical assistance with the design of the water maze; and Mr. Sami Minkkinen for technical assistance with the design of the patch rig. Support was provided by the Academy of Finland (296269 and 305834 to P.A.-L.); the Aalto Brain Centre (J.W.); Svenska kulturfonden (J.W.); the Finnish Society of Sciences and Letters (J.W.); the European Union's Horizon 2020 research and innovation programme (Marie Sklodowska-Curie grant 713645 to N.M.); the Doctoral programme Brain & Mind, University of Helsinki (S.K.); the Finnish Cultural Foundation (S.K.); the Ella and Georg Ehrnrooth Foundation (T.T.); the Oskar Öflund Foundation (T.T.); and the Finnish Foundation for Technology Promotion (T.T.). We acknowledge the computational resources provided by the Aalto Science-IT Project. Parts of Figure 1 and 4 were adapted from https://biorender.com. J.W. S.K. and P.A.-L. designed the experiments. T.T. developed the methodology for markerless mouse tracking. T.T. and S.K. set up the water maze used for behavioral experiments, and S.P carried out behavioral experiments. S.K. and S.P. collected and analyzed pupil data. N.M. carried out RGC experiments. J.W. S.K. and S.P. analyzed data. J.W. S.K. and P.A.-L wrote the MS. P.A.-L. is a founder and shareholder of Quantal Vision Technologies. T.T. and P.A.-L. have the following patents related to “a method for performing behavioral experiments with rodents”: FI127666B & US10706287B2. Perception of light in darkness requires no more than a handful of photons, and this remarkable behavioral performance can be directly linked to a particular retinal circuit—the retinal ON pathway. However, the neural limits of shadow detection in very dim light have remained unresolved. Here, we unravel the neural mechanisms that determine the sensitivity of mice (CBA/CaJ) to light decrements at the lowest light levels by measuring signals from the most sensitive ON and OFF retinal ganglion cell types and by correlating their signals with visually guided behavior. We show that mice can detect shadows when only a few photon absorptions are missing among thousands of rods. Behavioral detection of such “quantal” shadows relies on the retinal OFF pathway and is limited by noise and loss of single-photon signals in retinal processing. Thus, in the dim-light regime, light increments and decrements are encoded separately via the ON and OFF retinal pathways, respectively.

The aim of this study was to assess the occurrence and nature of retained dental roots and their associations with demographics in the Finnish adult population. From the cross-sectional nationwide Health 2000 Survey of the Finnish population aged 30 years and older, 6005 participants with clinical oral examination and panoramic radiographs were included. Occurrence and characteristics of all retained dental roots were examined. Statistical analyses included chi(2), Kruskal-Wallis and Mann-Whitney U tests, and SAS-SUDAAN calculations. The mean age of the 6005 participants (46% men and 54% women) was 53 (SD 14.6) years. At least one retained dental root was observed in 13% (n = 754) of the participants. The 1350 retained roots included 461 (34%) roots retained entirely in bone and 889 (66%) partly in bone. The most common location of a retained dental root was the third molar region. Occurrence of retained roots partly in bone was associated with male sex and lower education. Occurrence of retained third molar roots entirely in bone was associated with female sex, younger age, higher education, and living in a city. Among all retained dental roots, the preponderance of third molars emphasized the demanding nature of extracting the third molar in women.

At the sensitivity limit of vision, the quantal fluctuations of light and neural noise in the retina and the brain limit the detection of light signals. The challenge for vision, as for all senses, lies in separating the weakest signals from the neural noise originating within the sensory system. In this thesis, I studied sparse signal detection in the vertebrate visual system (mouse and frog) at low light levels from single retinal neurons to behavioral performance. First, we determined the sensitivity limit of amphibian color vision at low light levels. Unlike most vertebrates, amphibians are potential dichromats even at night, with two spectrally distinct classes of rod photoreceptors: common vertebrate rods (peak sensitivity at 500 nm) and an additional class called “green rods” (peak sensitivity at 430 nm). We showed that frogs in a phototaxis experiment can distinguish blue from green down to their absolute visual threshold, meaning that they have wavelength discrimination as soon as they start seeing anything. Remarkably, the behavioral blue/green discrimination approached theoretical limits set by photon fluctuations and rod noise, highlighting the sensitivity of the system comparing signals from the two different photoreceptors. Additionally, we show that the amphibian threshold for color discrimination is task- and context-dependent, underlining that sensory discrimination is not universally driven to absolute physical limits, but depends on evolutionary trade-offs and flexible brain states. In the second paper, we studied the impact of the circadian rhythm on the sensitivity limit of mouse vision. The retina has its own intrinsic circadian rhythms, which has led to the hypothesis that the sensitivity limit of vision would be under circadian control. We used a simple photon detection task, which allowed us to link well-defined retinal output signals to visually guided behavior. We found that mice have strikingly better performance in the visual task at night, so that they can reliably detect 10-fold dimmer light in the night than in the day. Interestingly, and contrary to previous hypotheses, this sensitivity difference did not arise in the retina, as assessed by spike recordings from retinal ganglion cells. Instead, mice utilize a more efficient search strategy in the task during the night. They are even able to apply the more efficient strategy at day once they have first performed the task during the night. Measured differences in search strategy explain only part of the day/night difference, however. We hypothesize that in addition there are diurnal changes in the state of brain circuits reading out the retinal input and making decisions. In the third paper, we determined the sensitivity limit of decrement (shadow) detection of mouse vision. Compared with the question of ultimate limit for detecting light, the question of sensitivity limits for detecting light decrements (negative contrast) has been remarkably neglected. We recorded the OFF responses of the most sensitive retinal ganglion cells at dim background light levels and correlated the thresholds to visually guided behavior in tightly matched conditions. We show that compared with an ideal-observer model most of the losses happen in the retina and remarkably, the behavioral performance is very close to an optimal read-out of the retinal ganglion cells. I have shown across visual tasks and in two different species how closely behavior in specific conditions can approach the performance limit set by physical constraints, rejecting noise and making use of every available photon. However, the actual performance strongly depends on the behavioral context and relevance of the task and state of the brain. Näön herkkyyden rajalla valokvanttien vähäinen määrä asettaa erityisen suuren haasteen näköjärjestelmän toiminnalle. Tällöin näköjärjestelmän on kyettävä erottamaan heikoimmatkin signaalit aistijärjestelmän sisäisestä kohinasta. Väitöskirjassani kysyn miten biologiset mekanismit vastaavat näihin haasteisiin. Selvitän hermoverkkojen signaalinkäsittelykykyä käyttäytymistä määrittävänä tekijänä, käyttäen mallina selkärankaisen (sammakko, hiiri) silmän verkkokalvon suorituskykyä lähellä näönherkkyyden rajaa. Tutkin näköaistin suorituskykyä yksittäisten verkkokalvon hermosolujen tasolta koko eläimen näönvaraiseen käyttäytymiseen. Ensimmäisessä osaprojektissa määritin heikoimman valointensiteetin missä sammakko pystyy erottamaan värejä. Toisin kuin muilla selkärankaisilla, sammakkoeläimillä on kaksi erityyppistä hämäränäköön erikoistunutta sauva-valoreseptoria: vihreän valon aallonpituutta parhaiten absorboiva viherherkkä sauvareseptori (kuten meillä) sekä lyhyempiä, sinisiä aallonpituuksia absorboiva siniherkkä sauva. Osoitimme, että sammakot pystyvät erottamaan värejä valaistuksessa, missä ihmiset eivät pysty. Tämä sini/viher-erotuskyky lähestyi teoreettisia fysikaalisia raja-arvoja. Lisäksi näytimme, että sammakkoeläinten värinäön kynnysherkkyys riippuu käyttäytymistehtävästä, korostaen kuinka aistinvarainen erotuskyky riippuu myös evolutiivisista valinnoista ja eläimen käyttäytymistilasta. Toisessa osatyössä tutkin vuorokausirytmin vaikutusta hiiren näönherkkyyteen. On oletettu, että verkkokalvon sopeutuu ennakoivasti valtaviin valon intensiteettimuutoksiin yön ja päivän välillä. Tässä työssä käytimme yksinkertaista, himmeiden valojen havaitsemistehtävää, joka mahdollisti verkkokalvon aivoihin lähettämän signaalin yhdistämisen näönvaraiseen käyttäytymiseen tiukan kvantitatiivisesti. Havaitsimme, että yöllä hiiret erottivat hyvin heikkoja valoja pimeässä jopa kymmenen kertaa paremmin kuin päivällä. Yllätykseksemme tämä ei johtunut muutoksista verkkokalvon maksimaalisessa herkkyydessä, vaan parempi suorituskyky yöllä johtui tehokkaammasta käyttäytymisstrategiasta sekä tarkemmasta näkötiedon käsittelystä aivoissa. Näytimme lisäksi, että hiiret pystyvät hyödyntämään tehokkaampaa strategiaa myös päiväsaikaan, jos ovat ensin suorittaneet tehtävän yöllä. Näkeminen vaatii sekä valojen että varjojen havaitsemista. Kolmannessa osaprojektissa määritin kuinka paljon fotoneja pitää poistaa heikosta taustavalosta, jotta hiiri havaitsee eron. Tämä kysymys on jäänyt verrattain huomiotta, verrattuna kymmenien vuosien tutkimukseen pienimmästä havaittavasta valomäärästä. Vertasimme herkimpien verkkokalvosolujen suorituskykyä näönvaraiseen käyttäytymiseen vastaavissa olosuhteissa. Näytimme verkkokalvon prosessointiin perustuvaa mallinnusta hyväksi käyttäen, että verrattuna teoreettisesti täydelliseen suorituskykyyn suurin osa informaationmenetyksistä tapahtuu verkkokalvolla fotonien pyydystämisessä ja verkkokalvon signaalinkäsittelyssä. Käyttäytyminen sen sijaan on huomattavan lähellä tilannetta, jossa aivot lukevat verkkokalvon lähettämää signaalia lähes täydellisesti. Väitöskirjassani näytän kahdella selkärankaisella, kuinka näkösuoritus pääsee useassa tehtävässä erittäin lähelle fysikaalisten reunaehtojen määräämiä raja-arvoja. Suorituskyky riippuu kuitenkin kontekstista ja käyttäytymistehtävän merkityksestä eläimelle sekä aivojen sen hetkisestä tilasta.

Background Shoulder disorders are common problems in primary health care. The course of disease of patients consulting for a new episode of a shoulder problem has been thought to be benign. In this prospective cohort study, we assessed the one-year consumption of medical resources and clinical outcome of shoulder disorders inclusive of all disease episodes. Methods All individuals consulting primary health care for shoulder disorder in a catchment area of more than 120 000 people were included. A composite questionnaire including the American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) was used to measure use of resources as well as shoulder pain and function. A follow-up assessment was performed after one year. Results A total of 128 individuals responded to the questionnaire. Only 24% of the patients had recovered after one year. Mean shoulder pain (Visual analogue scale, VAS, max 100 mm) decreased from 38.9 mm to 28.6 mm (95% CI -16.3 to -4.2 mm). The ASES score (max 100) improved significantly from 59.9 to 70.2 (95% CI 5.3 to 15.3). Mean one-year consumption of medical resources after the index consultation was 1.5 consultations, 0.5 radiological examinations, and 3.3 visits to physiotherapist. Mean resource-weighted direct costs were €543/patient/year (95% CI €351 to 735). Conclusions Shoulder disorders are often chronic and require a significant amount of resources from the health care system. The clinical outcome of the management of shoulder disorders in our study population including also individuals who have consulted previously for a shoulder problem is notably poorer than the one reported by previous studies on new episodes. However, despite the relatively modest outcome, subjective disability is low.