Miracle-dz/UniFAR-FTUs huggingface dataset:
A Dynamic Analysis of Household Dissolution and Living Arrangement Transitions by Elderly Americans

This paper exploits the new non-response files of the Panel Study of income Dynamics in order to study living arrangement transitions of elderly Americans. The focus of the paper is an estimate of the probability of household dissolution, i.e., the probabilities of transitions from living independently to living with adult children or other related or unrelated persons and the probability of becoming institutionalized, and an investigation of the factors causing such transitions. Our main result is an astounding stability of living arrangements even after incisive life-events such as death of a spouse, onset of a disability, or in the years immediately preceding death, in particular the large proportion of elderly who stay living independently until their deaths. Almost two thirds of all elderly are living independently in the year of their deaths. 14.4 percent share at least once housing with relatives or friends, 3.1 percent experience a stay in an institution. Old age, being male or of low income significantly increases the risk of institutionalization. Elderly with a large family and nonwhite elderly are the groups most likely to share housing. All this might be expected. An important new finding, however, is the time trend of these probabilities. Holding all other factors constant, the risk of institutionalization increased substantially between 1968 and 1984 while the likelihood of being "taken in" by relatives or friends markedly decreased.
A Selective Role for Dopamine in Learning to Maximize Reward But Not to Minimize Effort: Evidence from Patients with Parkinson's Disease

Instrumental learning is a fundamental process through which agents optimize their choices, taking into account various dimensions of available options such as the possible reward or punishment outcomes and the costs associated with potential actions. Although the implication of dopamine in learning from choice outcomes is well established, less is known about its role in learning the action costs such as effort. Here, we tested the ability of patients with Parkinson's disease (PD) to maximize monetary rewards and minimize physical efforts in a probabilistic instrumental learning task. The implication of dopamine was assessed by comparing performance ON and OFF prodopaminergic medication. In a first sample of PD patients (n = 15), we observed that reward learning, but not effort learning, was selectively impaired in the absence of treatment, with a significant interaction between learning condition (reward vs effort) and medication status (OFF vs ON). These results were replicated in a second, independent sample of PD patients (n = 20) using a simplified version of the task. According to Bayesian model selection, the best account for medication effects in both studies was a specific amplification of reward magnitude in a Q-learning algorithm. These results suggest that learning to avoid physical effort is independent from dopaminergic circuits and strengthen the general idea that dopaminergic signaling amplifies the effects of reward expectation or obtainment on instrumental behavior. SIGNIFICANCE STATEMENT Theoretically, maximizing reward and minimizing effort could involve the same computations and therefore rely on the same brain circuits. Here, we tested whether dopamine, a key component of reward-related circuitry, is also implicated in effort learning. We found that patients suffering from dopamine depletion due to Parkinson's disease were selectively impaired in reward learning, but not effort learning. Moreover, anti-parkinsonian medication restored the ability to maximize reward, but had no effect on effort minimization. This dissociation suggests that the brain has evolved separate, domain-specific systems for instrumental learning. These results help to disambiguate the motivational role of prodopaminergic medications: they amplify the impact of reward without affecting the integration of effort cost.
"Smouldering" Chronic Lymphocytic Leukemia.

Although clinical staging systems are useful to assess the prognosis of chronic lymphocyctic leukemia (CLL), for the large majority (up to 60%) of patients in early clinical stage no system is able to predict those who will progress ("active" disease) and those who will remain at the same stage ("smouldering" disease). To identify the latter subset of patients is important since in these patients treatment should be withhold until progression occurs. In the past few years, there have been several attempts to define "smouldering" CLL. Basically, patients in early stage (Binet's A) with: (a) moderate bone marrow infiltration (non-diffuse pattern in the biopsy or less than 80% lymphocytes in bone marrow aspirate), (b) low blood lymphocyte count (<30 × 10(9)/L), (c) Hb level in a non-anemic range (> 12 or 13 g/dL), and d) prolonged lymphocyte doubling time (> 12 months) are not likely to progress and have a life-expectancy not different from matched controls. In three different series analyzed so far, disease-progression rate is approximately 15% to 5 yrs, and survival is not different from that of controls. Approximately, 20 to 30% of all CLL patients with CLL fulfill "smouldering" criteria. Besides the above criteria, there are others that merit consideration. Thus, Rai's substages (AO vs AI + II) have been found to predict different outcomes within Binet's stage A. On the other hand, chromosome abnormalities may be useful to further assess the prognosis. Finally, the contribution of phenotypic studies to the definition of "smouldering" CLL remains uncertain, and a female sex has been associated with a better outcome. Whether or not patients with "active" stage A (e.g., those not fulfilling "smouldering" CLL criteria) should be treated is unknown. The morbidity associated to treatment (e.g. increase number of second neoplasms) and the lack of survival advantage found in recent randomized trials cast doubts on the real benefit of treating patients in early stage (Binet's A; Rai's 0). To answer this question, the separate analysis of patients with "smouldering" stage A and patients with "active" stage A included in recent trials could be of help. Moreover, prospective studies of patients in early stage followed-up with no treatment could be useful to refine the definition of "smouldering" CLL.
Cognitive therapy for the treatment of delusions

profile are gradually disclosed. Roberts (1991) describes some primary delusions as being potentially adaptive, leading to protection from depression and to an enhanced sense of meaning. Also, Harrow et al (1988)estimate that 70% of delusional ideas relate to non-delusional beliefs that pre-date the delusion. Delusions are, according to a number of researchers, points along a continuum with overvalued ideas and normal beliefs (Strauss, 1969; Chapman & Chapman, 1988; Jones & Watson, 1997). This continuum hypothesis, along with other research postulating that delusions are a reflection of a defensive attributional style protecting against low self-esteem (Lyon et al, 1994), provides the theoretical basis for many of the techniques and approaches used in the cognitive therapy of delusions. Cognitive therapy is a psychological treatment used nowadays in the majority of psychiatric disorders with differing levels of proven efficacy. It is active, directive, time-limited, structured and collaborative (Beck et al, 1979). Some time ago, there was a wider divide between cognitive therapy and cognitive-behavioural therapy. Cognitive therapy having a more cognitive focus, and being much more formulation driven, and focused on schema change, while cognitive-behavioural therapy was tradition ally more behaviourally oriented. Now the position is much less clear, with the terms cognitive therapy and cognitive-behavioural therapy being used more or less synonymously; in this paper, the terms cognitive therapy and cognitive-behavioural therapy refer to the same therapeutic stance and range of techniques. Most of the research on cognitive therapy so far has been done on depression. Cognitive therapy has been shown to be effective in both endogenous and non-endogenous depression (Blackburn et al, 1981) and also has a value in relapse prevention (Evans et al, 1992). Its efficacy in anxiety disorders (Blackburn & Davison, 1990) is relatively well known. Recent, randomised controlled trials which have been evaluating cognitive therapy in the treatment of schizophrenia are coming to fruition (Kuipersef al, 1997) to support an early promising but uncon trolled study (Kingdon & Turkington, 1991) indicating the potential benefits to be gained from this method of treating schizophrenia. The cognitive therapy approach to schizophrenia is much broader, including components directed towards coping skills (Tarrier et al, 1993), medication compliance (Kemp et al, 1996) and negative symptoms (Hogg, 1996). Delusions as treated within schizophrenia are tackled within this broader framework and techniques integrated within the overall direction of therapy (Fowler et al, 1995). In this situation one of the key predictors of response is cognitive flexibility concerning delusions (Garety et al, 1997). Huq et al (1988) have shown that deluded patients require less information and controls on probabilistic reasoning tasks and express greater certainty over their judgements; that is, deluded patients tend not
Prostatic Acid Phosphatase Reduces Thermal Sensitivity and Chronic Pain Sensitization by Depleting Phosphatidylinositol 4,5-Bisphosphate

Prostatic acid phosphatase (PAP) is expressed in nociceptive dorsal root ganglion (DRG) neurons, functions as an ectonucleotidase, and generates adenosine extracellularly. Here, we found that PAP inhibits noxious thermal sensitivity and sensitization that is associated with chronic pain through sustained activation of the adenosine A1 receptor (A1R) and phospholipase C-mediated depletion of phosphatidylinositol 4,5-bisphosphate (PIP2). In mice, intrathecal injection of PAP reduced PIP2 levels in DRGs, inhibited thermosensation through TRPV1, and enduringly reduced thermal hyperalgesia and mechanical allodynia caused by inflammation, nerve injury, and pronociceptive receptor activation. This included inhibitory effects on lysophosphatidic acid, purinergic (ATP), bradykinin, and protease-activated (thrombin) receptors. Conversely, PIP2 levels were significantly elevated in DRGs from Pap−/− mice, and this correlated with enhanced thermal hyperalgesia and mechanical allodynia in Pap−/− mice. To directly test the importance of PIP2 in nociception, we intrathecally injected PIP2 into mice. This transiently (2 h) elevated PIP2 levels in lumbar DRGs and transiently (2 h) enhanced thermosensation. Additionally, thermal hyperalgesia and mechanical allodynia were enduringly enhanced when PIP2 levels were elevated coincident with injury/pronociceptive receptor stimulation. Nociceptive sensitization was not affected if PIP2 levels were elevated in the absence of ongoing pronociceptive receptor stimulation. Together, our data suggest that PIP2 levels in DRGs directly influence thermosensation and the magnitude of nociceptive sensitization. Moreover, our data suggest there is an underlying “phosphoinositide tone” that can be manipulated by an adenosine-generating ectonucleotidase. This tone regulates how effectively acute nociceptive insults promote the transition to chronic pain.
Nuclear interactor of ARF and Mdm2 regulates multiple pathways to activate p53

The p53 tumor suppressor is controlled by an interactive network of factors that stimulate or inhibit its transcriptional activity. Within that network, Mdm2 functions as the major antagonist of p53 by promoting its ubiquitylation and degradation. Conversely, Tip60 activates p53 through direct association on target promoters as well as acetylation of p53 at lysine 120 (K120). This study examines the functional relationship between Mdm2 and Tip60 with a novel p53 regulator, NIAM (nuclear interactor of ARF and Mdm2). Previous work showed NIAM can suppress proliferation and activate p53 independently of ARF, indicating that other factors mediate those activities. Here, we demonstrate that NIAM is a chromatin-associated protein that binds Tip60. NIAM can promote p53 K120 acetylation, although that modification is not required for NIAM to inhibit proliferation or induce p53 transactivation of the p21 promoter. Notably, Tip60 silencing showed it contributes to but is not sufficient for NIAM-mediated p53 activation, suggesting other mechanisms are involved. Indeed, growth-inhibitory forms of NIAM also bind to Mdm2, and increased NIAM expression levels disrupt p53–Mdm2 association, inhibit p53 polyubiquitylation, and prevent Mdm2-mediated inhibition of p53 transcriptional activity. Importantly, loss of NIAM significantly impairs p53 activation. Together, these results show that NIAM activates p53 through multiple mechanisms involving Tip60 association and Mdm2 inhibition. Thus, NIAM regulates 2 critical pathways that control p53 function and are altered in human cancers, implying an important role for NIAM in tumorigenesis.
A Subconscious Interaction between Fixation and Anticipatory Pursuit

Ocular smooth pursuit and fixation are typically viewed as separate systems, yet there is evidence that the brainstem fixation system inhibits pursuit. Here we present behavioral evidence that the fixation system modulates pursuit behavior outside of conscious awareness. Human observers (male and female) either pursued a small spot that translated across a screen, or fixated it as it remained stationary. As shown previously, pursuit trials potentiated the oculomotor system, producing anticipatory eye velocity on the next trial before the target moved that mimicked the stimulus-driven velocity. Randomly interleaving fixation trials reduced anticipatory pursuit, suggesting that a potentiated fixation system interacted with pursuit to suppress eye velocity in upcoming pursuit trials. The reduction was not due to passive decay of the potentiated pursuit signal because interleaving “blank” trials in which no target appeared did not reduce anticipatory pursuit. Interspersed short fixation trials reduced anticipation on long pursuit trials, suggesting that fixation potentiation was stronger than pursuit potentiation. Furthermore, adding more pursuit trials to a block did not restore anticipatory pursuit, suggesting that fixation potentiation was not overridden by certainty of an imminent pursuit trial but rather was immune to conscious intervention. To directly test whether cognition can override fixation suppression, we alternated pursuit and fixation trials to perfectly specify trial identity. Still, anticipatory pursuit did not rise above that observed with an equal number of random fixation trials. The results suggest that potentiated fixation circuitry interacts with pursuit circuitry at a subconscious level to inhibit pursuit. SIGNIFICANCE STATEMENT When an object moves, we view it with smooth pursuit eye movements. When an object is stationary, we view it with fixational eye movements. Pursuit and fixation are historically regarded as controlled by different neural circuitry, and alternating between invoking them is thought to be guided by a conscious decision. However, our results show that pursuit is actively suppressed by prior fixation of a stationary object. This suppression is involuntary, and cannot be avoided even if observers are certain that the object will move. The results suggest that the neural fixation circuitry is potentiated by engaging stationary objects, and interacts with pursuit outside of conscious awareness.
Past, Present and Future of Hospice in Korea

호스피스는 머지않아 임종이 예견되는 환자와 가족들 이 가지고 있는 육체적, 정신적, 영적, 경제적, 사회 적, 문화적 문제들을 의사와 간호사를 포함하는 의료인 뿐 만 아니라 여러가지 문제 해결을 도와줄 각 분야의 전문가 들이하나의팀을구성하여상호보완적인위치에서최선을 다 함으로써 환자와 가족의 고통을 덜어주고 삶의 질의 극 대화하여 행복하고 편안한 가운데에서 인간으로서의 존엄 성을유지하면서임종을맞이하도록돕고나아가서환자임 종 후에 남는 가족들의 사별의 슬픔까지 도와주는 행위를 말한다(1). 1965년에처음시작된한국의호스피스는이제 청년기를 넘어 장년기로 들어가고 있다. 그러나 아직 호스 피스의개념정립이미흡하고제도자체가미성숙하여국민 들의 호스피스에 대한 요구를 충족하기에 부족함이 많다. 정부의 호스피스에 대한 정책은 최근 들어 제자리를 잡기 시작하였으며, 바야흐로호스피스법의제정과수가에대한 기준이 마련되는 등 제도화를 위한 준비가 진행되고 있는 한국 호스피스의 과거, 현재, 미래
Multistate Structural Modeling and Voltage-Clamp Analysis of Epilepsy/Autism Mutation Kv10.2–R327H Demonstrate the Role of This Residue in Stabilizing the Channel Closed State

Voltage-gated potassium channel Kv10.2 (KCNH5) is expressed in the nervous system, but its functions and involvement in human disease are poorly understood. We studied a human Kv10.2 channel mutation (R327H) recently identified in a child with epileptic encephalopathy and autistic features. Using multistate structural modeling, we demonstrate that the Arg327 residue in the S4 helix of voltage-sensing domain has strong ionic interactions with negatively charged residues within the S1–S3 helices in the resting (closed) and early-activation state but not in the late-activation and fully-activated (open) state. The R327H mutation weakens ionic interactions between residue 327 and these negatively charged residues, thus favoring channel opening. Voltage-clamp analysis showed a strong hyperpolarizing (∼70 mV) shift of voltage dependence of activation and an acceleration of activation. Our results demonstrate the critical role of the Arg327 residue in stabilizing the channel closed state and explicate for the first time the structural and functional change of a Kv10.2 channel mutation associated with neurological disease.
Activity of Tachykinin1-Expressing Pet1 Raphe Neurons Modulates the Respiratory Chemoreflex

Homeostatic control of breathing, heart rate, and body temperature relies on circuits within the brainstem modulated by the neurotransmitter serotonin (5-HT). Mounting evidence points to specialized neuronal subtypes within the serotonergic neuronal system, borne out in functional studies, for the modulation of distinct facets of homeostasis. Such functional differences, read out at the organismal level, are likely subserved by differences among 5-HT neuron subtypes at the cellular and molecular levels, including differences in the capacity to coexpress other neurotransmitters such as glutamate, GABA, thyrotropin releasing hormone, and substance P encoded by the Tachykinin-1 (Tac1) gene. Here, we characterize in mice a 5-HT neuron subtype identified by expression of Tac1 and the serotonergic transcription factor gene Pet1, referred to as the Tac1-Pet1 neuron subtype. Transgenic cell labeling showed Tac1-Pet1 soma resident largely in the caudal medulla. Chemogenetic [clozapine-N-oxide (CNO)-hM4Di] perturbation of Tac1-Pet1 neuron activity blunted the ventilatory response of the respiratory CO2 chemoreflex, which normally augments ventilation in response to hypercapnic acidosis to restore normal pH and PCO2. Tac1-Pet1 axonal boutons were found localized to brainstem areas implicated in respiratory modulation, with highest density in motor regions. These findings demonstrate that the activity of a Pet1 neuron subtype with the potential to release both 5-HT and substance P is necessary for normal respiratory dynamics, perhaps via motor outputs that engage muscles of respiration and maintain airway patency. These Tac1-Pet1 neurons may act downstream of Egr2-Pet1 serotonergic neurons, which were previously established in respiratory chemoreception, but do not innervate respiratory motor nuclei. SIGNIFICANCE STATEMENT Serotonin (5-HT) neurons modulate physiological processes and behaviors as diverse as body temperature, respiration, aggression, and mood. Using genetic tools, we characterize a 5-HT neuron subtype defined by expression of Tachykinin1 and Pet1 (Tac1-Pet1 neurons), mapping soma localization to the caudal medulla primarily and axonal projections to brainstem motor nuclei most prominently, and, when silenced, observed blunting of the ventilatory response to inhaled CO2. Tac1-Pet1 neurons thus appear distinct from and contrast previously described Egr2-Pet1 neurons, which project primarily to chemosensory integration centers and are themselves chemosensitive.
Higher-Order Sensory Cortex Drives Basolateral Amygdala Activity during the Recall of Remote, but Not Recently Learned Fearful Memories

Negative experiences are quickly learned and long remembered. Key unresolved issues in the field of emotional memory include identifying the loci and dynamics of memory storage and retrieval. The present study examined neural activity in the higher-order auditory cortex Te2 and basolateral amygdala (BLA) and their crosstalk during the recall of recent and remote fear memories. To this end, we obtained local field potentials and multiunit activity recordings in Te2 and BLA of rats that underwent recall at 24 h and 30 d after the association of an acoustic conditioned (CS, tone) and an aversive unconditioned stimulus (US, electric shock). Here we show that, during the recall of remote auditory threat memories in rats, the activity of the Te2 and BLA is highly synchronized in the theta frequency range. This functional connectivity stems from memory consolidation processes because it is present during remote, but not recent, memory retrieval. Moreover, the observed increase in synchrony is cue and region specific. A preponderant Te2-to-BLA directionality characterizes this dialogue, and the percentage of time Te2 theta leads the BLA during remote memory recall correlates with a faster latency to freeze to the auditory conditioned stimulus. The blockade of this information transfer via Te2 inhibition with muscimol prevents any retrieval-evoked neuronal activity in the BLA and animals are unable to retrieve remote memories. We conclude that memories stored in higher-order sensory cortices drive BLA activity when distinguishing between learned threatening and neutral stimuli. SIGNIFICANCE STATEMENT How and where in the brain do we store the affective/motivational significance of sensory stimuli acquired through life experiences? Scientists have long investigated how “limbic” structures, such as the amygdala, process affective stimuli. Here we show that retrieval of well-established threat memories requires the functional interplay between higher-order components of the auditory cortex and the amygdala via synchrony in the theta range. This functional connectivity is a result of memory consolidation processes and is characterized by a predominant cortical to amygdala direction of information transfer. This connectivity is predictive of the animals' ability to recognize auditory stimuli as aversive. In the absence of this necessary cortical activity, the amygdala is unable to distinguish between frightening and neutral stimuli.
Appraising clinical guidelines and the development of criteria-a pilot study

In the past few years there has been a remarkable rise in the publication of clinical practice guidelines in the UK. Guidelines are being produced for many conditions from a variety of sources. Increasingly, health care practitioners are encouraged to use guidelines to promote the quality and cost-effectiveness of the care they provide. Yet important questions remain unanswered. How do we judge the quality of guidelines? What criteria should we use to make that judgement? Following a national workshop, a joint programme was set up to research and develop methods for evaluating clinical practice guidelines. This paper presents the results of a pilot study on the appraisal of a number of UK published guidelines using a multidisciplinary review panel. If the introduction of guidelines is to improve the quality of care, users must be able to judge the rigour with which the guidelines have been produced. The results of this study suggest that UK guidelines are deficient in the information necessary to make thi.