Distinct Onset Research Articles

Chronisch progressief lymfoedeem bij het Belgisch trekpaard in België: klinische fenotypering, prevalentie en analyse van risicofactoren

Het Belgisch trekpaard is belast met chronisch progressief lymfoedeem (CPL), een bekende, ongeneeslijke aandoening. Tot op heden bestaat er geen uniform diagnostisch protocol, waardoor een goede schatting van de prevalentie onbestaande is. Het doel van dit artikel was een eenduidige klinische onderzoeksmethode te ontwikkelen om de objectiviteit van de CPL-diagnose te verhogen en de prevalentie van CPL bij het Belgisch trekpaard na te gaan. Daarnaast werd aan de hand van statistische modellen het verband onderzocht tussen bepaalde factoren, zoals de interactie leeftijd-geslacht, vachtkleur en seizoen, enerzijds en het optreden van klinische symptomen anderzijds. Deze studie toont aan dat de prevalentie van CPL hoog is. In de volledige steekproef, waarbij een groot aandeel van de paarden jonger was dan drie jaar, was 60,66% aangetast. In een subset van oudere dieren (≥ 3 jaar) was dat 85,86%. Bij sommige paarden werden reeds milde symptomen gezien vanaf één jaar (14% van de jaarlingen), maar duidelijke letsels kwamen doorgaans voor vanaf de leeftijd van drie jaar. Het ontwikkelde protocol kan de CPL-diagnose en toekomstige gegevensverzameling vergemakkelijken. In de voorliggende studie werden factoren die significant geassocieerd zijn met CPL, i. e. interactie leeftijd-geslacht, vachtkleur en seizoen, geïdentificeerd en gekwantificeerd. Daarmee is de basis gelegd voor kwantitatief genetisch onderzoek met als ultiem doel CPL bij het Belgisch trekpaard te reduceren.

Risk factors across the eating disorders

This study sought to examine risk and onset patterns in anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). Women with AN (n=71), BN (n=66), BED (n=160) and non-psychiatric controls (n=323) were compared retrospectively on risk factors, symptom onset, and diagnostic migration. Eating disorder groups reported greater risk exposure than non-psychiatric controls. AN and BED differed on premorbid personality/behavioral problems, childhood obesity, and family overeating. Risk factors for BN were shared with AN and BED. Dieting was the most common onset symptom in AN, whereas binge eating was most common in BN and BED. Migration between AN and BED was rare, but more frequent between AN and BN and between BN and BED. AN and BED have distinct risk factors and onset patterns, while BN shares similar risk factors and onset patterns with both AN and BED. Results should inform future classification schemes and prevention programs.

EPA-0058 – Delusional disorder in a man with anorexia nervosa: a case-report

Anorexia nervosa (AN) is a syndrome characterized by three essential criteria. The first is a self-induced starvation, the second is a relentless drive for thinness or a morbid fear of fatness and the third is the presence of medical signs and symptoms resulting from starvation. The most common ages of onset of anorexia nervosa are the mid teens. It occurs 10 to 20 times more often in females than males and it seems to be more frequent in developed countries. In some patients concerns about weight reaches delusional proportions. This subpopulation of patients warrants further study since patients with more delusional beliefs may have a form of AN that is more refractory to treatment. In this report a rare case of Anorexia nervosa is presented in which the patient is a 29 year old male with poor socioeconomic background from a developing country who subsequently experienced a distinct onset of delusional disorder. After four weeks delusional disorder and Anorexia Nervosa resolved due to treatment by atypical antipsychotics (Risperidone).

Sonorant Onset Pitch as a Perceptual Cue of Lexical Tones in Mandarin

Lexical tone identification requires a number of secondary cues, when main tonal contours are unavailable. In this article, we examine Mandarin native speakers' ability to identify lexical tones by extracting tonal information from sonorant onset pitch (onset contours) on syllable-initial nasals ranging from 50to 70 ms in duration. In experiments I and II we test speakers' ability to identify lexical tones in a second syllable with and without onset contours in isolation (experiment I) and in a sentential context (experiment II). The results indicate that speakers can identify lexical tones with short distinctive onset contour patterns,they also indicate that misperception of tones 213 and 24 are common. Furthermore, in experiment III, we test whether onset contours in a following syllable can be utilized by listeners in tone identification. We find that onset contours in the following syllable also contribute to the identification of the target lexical tones. The conclusions are twofold: (1) Mandarin lexical tones can be identified with onset contours; (2) tonal domain must be extended to include not just typical cues of tones but also coarticulated tonal patterns.

Drug delivery to the brain by focused ultrasound induced blood–brain barrier disruption: Quantitative evaluation of enhanced permeability of cerebral vasculature using two-photon microscopy

Reversible and localized blood–brain barrier disruption (BBBD) using focused ultrasound (FUS) in combination with intravascularly administered microbubbles (MBs) has been established as a non-invasive method for drug delivery to the brain. Using two-photon fluorescence microscopy (2PFM), we imaged the cerebral vasculature during BBBD and observed the extravasation of fluorescent dye in real-time in vivo. We measured the enhanced permeability upon BBBD for both 10kDa and 70kDa dextran conjugated Texas Red (TR) at the acoustic pressure range of 0.2–0.8MPa and found that permeability constants of TR10kDa and TR70kDa vary from 0.0006 to 0.0359min−1 and from 0.0003 to 0.0231min−1, respectively. For both substances, a linear regression was applied on the permeability constant against the acoustic pressure and the slope from best-fit was found to be 0.039±0.005min−1/MPa and 0.018±0.005min−1/MPa, respectively. In addition, the pressure threshold for successfully induced BBBD was confirmed to be 0.4–0.6MPa. Finally, we identified two types of leakage kinetics (fast and slow) that exhibit distinct permeability constants and temporal disruption onsets, as well as demonstrated their correlations with the applied acoustic pressure and vessel diameter. Direct assessment of vascular permeability and insights on its dependency on acoustic pressure, vessel size and leakage kinetics are important for treatment strategies of BBBD-based drug delivery.

461 – Delusional disorder in an iranian man with anorexia nervosa: a case report

Introduction Anorexia Nervosa is a serious mental illness and is frequently seen in young females in childhood and adolescence. The most common ages of onset of anorexia nervosa are the mid teens. Objectives To our knowledge this is singular report of a case of delusional disorder in which Anorexia Nervosa preceded the onset of psychotic symptoms. Age and sex of our case are unusual in Anorexia nervosa. Aim In this report a rare case of Anorexia nervosa is presented in which the patient is a 32 year old male with poor socioeconomic background from a developing country who subsequently experienced a distinct onset of delusional disorder. After four weeks, delusional disorder and Anorexia Nervosa resolved due to treatment by atypical antipsychotics (Risperidone). Results The association between anorexia Nervosa and Delusional Disorder is important. In the case which is reported here delusional thoughts started six month after anorexia nervosa when the patient became extremely thin and cachectic. Conclusion In fact the theory of occurrence of psychotic disorder as a result of severe malnutrition is intensified.

Enfermedad de Wilson: espectro clínico de la enfermedad hepática

Wilson's disease is a hereditary autosomal recessive disorder of copper metabolism,characterized by copper accumulation in the liver and brain. This rare entity, which has a broad clinical spectrum, is often difficult to diagnose and should therefore always be suspected in patients with liver disease of unclear cause. We describe two types of manifestation of liver disease in two patients; the first developed fulminant hepatic failure requiring urgent liver transplantation and the second showed advanced chronic liver disease and received standard medical treatment. The objective of this clinical observation is to analyze the diagnosis of Wilson's disease in two patients with distinct onset, illustrating the broad clinical spectrum of the disease, and its treatment.

Gbx2 Plays an Essential but Transient Role in the Formation of Thalamic Nuclei

Unlike the laminar arrangement of neurons in the neocortex, thalamic neurons aggregate to form about dozens of nuclei, many of which make topographic connections with specific areas in the neocortex. The molecular mechanisms underlying the formation of thalamic nuclei remain largely unknown. Homeodomain transcription factor Gbx2 is specifically expressed in the developing thalamus. Deleting Gbx2 leads to severe disruption of the histogenesis of the thalamus in mice, demonstrating an essential role of Gbx2 in this brain structure. Using inducible genetic fate mapping, we have previously shown that the neuronal precursors for different sets of thalamic nuclei have distinctive onset and duration of Gbx2 expression, suggesting that the dynamic expression of Gbx2 plays an important role in the specification and differentiation of thalamic nuclei. Here, we showed that the Gbx2 lineage exclusively gives rise to neurons but not glia in the thalamus. We performed conditional deletion to examine the temporal requirements of Gbx2 in the developing thalamus in mice. Corresponding to the dynamic and differential expression of Gbx2 in various thalamic nucleus groups, deleting Gbx2 at different embryonic stages disrupts formation of distinct sets of thalamic nuclei. Interestingly, different thalamic nuclei have remarkably different requirements of Gbx2 for the survival of thalamic neurons. Furthermore, although Gbx2 expression persists in many thalamic nuclei until adulthood, only the initial expression of Gbx2 following neurogenesis is crucial for the differentiation of thalamic nuclei. Our results indicate that the dynamic expression of Gbx2 may act as an important determinant in coupling with other developmental programs to generate distinct thalamic nuclei.

Paired-Pulse Plasticity in the Strength and Latency of Light-Evoked Lateral Inhibition to Retinal Bipolar Cell Terminals

Synapses in the inner plexiform layer of the retina undergo short-term plasticity that may mediate different forms of adaptation to regularities in light stimuli. Using patch-clamp recordings from axotomized goldfish Mb bipolar cell (BC) terminals with paired-pulse light stimulation, we isolated and quantified the short-term plasticity of GABAergic lateral IPSCs (L-IPSCs). Bright light stimulation evoked ON and OFF L-IPSCs in axotomized BCs, which had distinct onset latencies (∼50-80 and ∼70-150 ms, respectively) that depended on background light adaptation. We observed plasticity in both the synaptic strength and latency of the L-IPSCs. With paired light stimulation, latencies of ON L-IPSCs increased at paired-pulse intervals (PPIs) of 50 and 300 ms, whereas OFF L-IPSC latencies decreased at the 300 ms PPI. ON L-IPSCs showed paired-pulse depression at intervals <1 s, whereas OFF L-IPSCs showed depression at intervals ≤1 s and amplitude facilitation at longer intervals (1-2 s). This biphasic form of L-IPSC plasticity may underlie adaptation and sensitization to surround temporal contrast over multiple timescales. Block of retinal signaling at GABA(A)Rs and AMPARs differentially affected ON and OFF L-IPSCs, confirming that these two types of feedback inhibition are mediated by distinct and convergent retinal pathways with different mechanisms of plasticity. We propose that these plastic changes in the strength and timing of L-IPSCs help to dynamically shape the time course of glutamate release from ON-type BC terminals. Short-term plasticity of L-IPSCs may thus influence the strength, timing, and spatial extent of amacrine and ganglion cell inhibitory surrounds.

Logistic model of glucose-regulated C-peptide secretion: hysteresis pathway disruption in impaired fasting glycemia

The present analysis tests the hypothesis that quantifiable disruption of the glucose-stimulated insulin-secretion dose-response pathway mediates impaired fasting glycemia (IFG) and type 2 diabetes mellitus (DM). To this end, adults with normal and impaired fasting glycemia (NFG, n = 30), IFG (n = 32), and DM (n = 14) were given a mixed meal containing 75 g glucose. C-peptide and glucose were measured over 4 h, 13 times in NFG and IFG and 16 times in DM (age range 50-57 yr, body mass index 28-32 kg/m(2)). Wavelet-based deconvolution analysis was used to estimate time-varying C-peptide secretion rates. Logistic dose-response functions were constructed analytically of the sensitivity, potency, and efficacy (in the pharmacological sense of slope, one-half maximal stimulation, and maximal effect) of glucose's stimulation of prehepatic insulin (C-peptide) secretion. A hysteresis changepoint time, demarcating unequal glucose potencies for onset and recovery pathways, was estimated simultaneously. According to this methodology, NFG subjects exhibited distinct onset and recovery potencies of glucose in stimulating C-peptide secretion (6.5 and 8.5 mM), thereby defining in vivo hysteresis (potency shift -2.0 mM). IFG patients manifested reduced glucose onset potency (8.6 mM), and diminished C-peptide hysteretic shift (-0.80 mM). DM patients had markedly decreased glucose potency (18.8 mM), reversal of C-peptide's hysteretic shift (+4.5 mM), and 30% lower C-peptide sensitivity to glucose stimulation. From these data, we conclude that a dynamic dose-response model of glucose-dependent control of C-peptide secretion can identify disruption of in vivo hysteresis in patients with IFG and DM. Pathway-defined analytic models of this kind may aid in the search for prediabetes biomarkers.

Lack of association between filaggrin gene mutations and onset of psoriasis in childhood

Atopic dermatitis (AD; OMIM#603165) and psoriasis (OMIM#177900) are two common inflammatory skin disorders. Both are genetically complex, multifactorial and do not follow a Mendelian pattern of inheritance. Both diseases share several genetic susceptibility loci such as the epidermal differentiation complex (EDC) on chromosome 1q21. Within the EDC, mutations in the filaggrin (FLG) gene are strongly associated with AD whereas no association has been replicated with psoriasis. However, reduced levels of filaggrin have been reported in psoriatic skin. Further, filaggrin deficiency was shown to be a modifying factor for the phenotype in another epidermal skin disorder, X-linked recessive ichthyosis. Altogether, this raises the question if FLG mutations may modify the disease course in other epidermal skin diseases such as psoriasis. Psoriasis is a highly heterogeneous disease and so far genetic studies have not taken the distinct sub-phenotype childhood onset into account. To determine if FLG mutations modify the onset of psoriasis. A total of 241 children with onset of psoriasis below 15 years of age and 314 healthy controls were identified at the Dermatology clinic, Karolinska University Hospital and diagnosed by the same dermatologist (JL). Blood samples were taken and medical history was recorded. FLG was genotyped in all patients and controls using allelic discrimination (n = 555) and sequencing (n = 20). No association between FLG mutations and early onset of psoriasis was demonstrated (P = 0.57) and no novel mutations were detected, indicating that FLG loss-of-function variants do not have a strong effect on the onset of psoriasis in childhood.

Increased familiarity of intellectual deficits in early-onset schizophrenia spectrum disorders

Objectives. Early-onset schizophrenia is considered to be neurobiologically similar to adult-onset forms, although it represents a more severe expression of the disorder. In the present study, we explored putative larger familial vulnerability of intellectual impairments in early-onset schizophrenia spectrum disorders (EOS) when compared to adult-onset (AOS) families. Methods. A sample of 340 subjects including schizophrenia spectrum disorder patients, their first degree relatives and age-matched healthy controls was assessed on intelligence quotient (IQ). We used linear regression analysis and intraclass correlation coefficients (ICC) to explore familial aggregation of IQ across age at onset groups. Results. The relationship between IQ level of patients and their first-degree relatives showed positive linear association (β = 0.43, P < 0.01). High significant familial aggregation was found for intelligence quotient in EOS families (ICC = 0.618, P < 0.01), while AOS families responded to lower estimates (ICC = 0.204, P = 0.26; between ICC comparison z = 1.993, P < 0.05). Conclusions. High aggregation of intellectual performance in the EOS group suggests larger familial vulnerability in early-onset forms of the disease when cognitive functions are considered. Within a continuum of psychopathology in schizophrenia spectrum disorders, specific genetic effects are discussed for distinct onset forms that might be in line with a neurodevelopmental model of the disease.

Management and Outcomes in Pediatric Patients Presenting with Acute Fulminant Myocarditis

To investigate factors associated with mechanical circulatory support and survival in patients with acute fulminant myocarditis (AFM). Retrospective cohort of AFM patients admitted to the cardiac intensive care unit during 1996-2008. AFM was defined as distinct onset of symptoms ≤14 days before admission, rapid-onset cardiogenic shock, and normal left ventricular size. Demographic and physiological variables were compared between patients treated with extracorporeal membrane oxygenation (ECMO) and those who were not and between survivors and nonsurvivors. Twenty patients (median age 12.7 years) met inclusion criteria. Seventeen patients (85%) survived to hospital discharge. One underwent heart transplantation. Ten (50%) patients required ECMO, and 7 (70%) of these survived. On admission, patients requiring ECMO had elevated lactate (9 vs 1 mmol/L), creatinine (0.8 vs 0.6 mg/dL), and aspartate aminotransferase (256 vs 35 IU/L) (all P < .05) and a trend towards increased incidence of dysrhythmias (80% vs 30%, P = .07). During hospitalization, non-survivors had higher peak lactate (10 vs 3 mmol/L), creatinine (1.5 vs 0.8 mg/dL), and aspartate aminotransferase (3007 vs 156 IU/L) (all P < .05) compared with survivors. Patients with AFM with end organ dysfunction or arrhythmias on admission may require mechanical circulatory support. The transplant-free survival rate in this critically ill cohort was excellent (80%).

40Ar/39Ar chronostratigraphy of Altiplano-Puna volcanic complex ignimbrites reveals the development of a major magmatic province

The Lipez region of southwest Bolivia is the locus of a major Neogene ignimbrite flare-up, and yet it is the least studied portion of the Altiplano-Puna volcanic complex of the Central Andes. Recent mapping and laser-fusion 40 Ar/ 39 Ar dating of sanidine and biotite from 56 locations, coupled with paleomagnetic data, refine the timing and volumes of ignimbrite emplacement in Bolivia and northern Chile to reveal that monotonous intermediate volcanism was prodigious and episodic throughout the complex. The new results unravel the eruptive history of the Pastos Grandes and Guacha calderas, two large multicyclic caldera complexes located in Bolivia. These two calderas, together with the Vilama and La Pacana caldera complexes and smaller ignimbrite shields, were the dominant sources of the ignimbrite-producing eruptions during the ∼10 m.y. history of the Altiplano-Puna volcanic complex. The oldest ignimbrites erupted between 11 and 10 Ma represent relatively small volumes (approximately hundreds of km 3 ) of magma from sources distributed throughout the volcanic complex. The first major pulse was manifest at 8.41 Ma and 8.33 Ma as the Vilama and Sifon ignimbrites, respectively. During pulse 1, at least 2400 km 3 of dacitic magma was erupted over 0.08 m.y. Pulse 2 involved near-coincident eruptions from three of the major calderas resulting in the 5.60 Ma Pujsa, 5.65 Ma Guacha, and 5.45 Ma Chuhuilla ignimbrites, for a total minimum volume of 3000 km 3 of magma. Pulse 3, the largest, produced at least 3100 km 3 of magma during a 0.1 m.y. period centered at 4 Ma, with the eruption of the 4.09 Ma Puripicar, 4.00 Ma Chaxas, and 3.96 Ma Atana ignimbrites. This third pulse was followed by two more volcanic explosivity index (VEI) 8 eruptions, producing the 3.49 Ma Tara (800 km 3 DRE) and 2.89 Ma Pastos Grandes (1500 km 3 DRE) ignimbrites. In addition to these large caldera-related eruptions, new age determinations refine the timing of two little-known ignimbrite shields, the 5.23 Ma Alota and 1.98 Ma Laguna Colorada centers. Moreover, 40 Ar/ 39 Ar age determinations of 13 ignimbrites from northern Chile previously dated by the K-Ar method improve the overall temporal resolution of Altiplano-Puna volcanic complex development. Together with the updated volume estimates, the new age determinations demonstrate a distinct onset of Altiplano-Puna volcanic complex ignimbrite volcanism with modest output rates, an episodic middle phase with the highest eruption rates, followed by a decline in volcanic output. The cyclic nature of individual caldera complexes and the spatiotemporal pattern of the volcanic field as a whole are consistent with both incremental construction of plutons as well as a composite Cordilleran batholith.

Spin-polarized spin excitation spectroscopy

We report on the spin dependence of elastic and inelastic electron tunneling through transition metal atoms. Mn, Fe and Cu atoms were deposited onto a monolayer of Cu2N on Cu(100) and individually addressed with the probe tip of a scanning tunneling microscope. Electrons tunneling between the tip and the substrate exchange energy and spin angular momentum with the surface-bound magnetic atoms. The conservation of energy during the tunneling process results in a distinct onset threshold voltage above which the tunneling electrons create spin excitations in the Mn and Fe atoms. Here we show that the additional conservation of spin angular momentum leads to different cross-sections for spin excitations depending on the relative alignment of the surface spin and the spin of the tunneling electron. For this purpose, we developed a technique for measuring the same local spin with a spin-polarized and a non-spin-polarized tip by exchanging the last apex atom of the probe tip between different transition metal atoms. We derive a quantitative model describing the observed excitation cross-sections on the basis of an exchange scattering process.

Distribution of late potentials within infarct scars assessed by ultra high-density mapping

Late potential (LP) electrograms represent areas of slow conduction and are often sites critical to reentrant tachycardia circuits. The distribution of LPs within infarct scar is not known. The purpose of this study was to delineate infarct heterogeneity using ultra high-density mapping and to determine the location of LPs with respect to scar architecture. Detailed endocardial (n = 21) and epicardial (n = 8) ultra high-density mapping was performed to delineate the substrate for ventricular tachycardia (VT) in 21 patients with ischemic cardiomyopathy. LP was defined as a low-voltage electrogram (< 1.5 mV) with distinct onset after the QRS. Very late potentials (vLPs) were classified as LPs with onset > 100 ms after the QRS. A mean of 787 ± 391 and 810 ± 375 points in the LV endocardium and epicardium were sampled. Multipolar mapping identified heterogeneous islets (HIs) with relatively preserved electrogram amplitudes (≥ 0.51 mv) within dense scar (8.5 ± 4.9/4.5 ± 2.6 HIs per endocardium/epicardium) in all patients. In maps on which putative VT isthmuses were identified (25/29), 57% of vLP were recorded in or adjacent to HI. An LP-targeted ablation strategy combined with pace mapping achieved acute success in all patients (complete success in 52% and partial success in 48%). After 15 ± 7 months, 65% of patients remained free of VT episodes. Ultra high-density mapping with a multipolar catheter facilitates the delineation of heterogeneous scar architecture at higher resolution. Electrograms within and adjacent to HIs have a higher incidence of vLP, and these sites are frequently critical to reentry. These findings have important implications for substrate-based ablation strategies.

Spatio-temporal evolution of volcano seismicity: A laboratory study

We report a laboratory and microstructural study of a suite of deformation experiments in which basalt from Mount Etna volcano is deformed and fractured at an effective confining pressure representative of conditions under a volcanic edifice (40 MPa). Particular attention was paid to the formation of a fracture and damage zone with which to stimulate coupled hydro-mechanical interactions that create the various types of seismicity recorded on volcanic edifices, and which usually precede eruption. Location of AE events through time shows the formation of a fault plane during which waveforms exhibit the typical high frequency characteristics of volcano-tectonic (VT) earthquakes. We found that these VT earthquakes were particularly pronounced when generated using dry samples, compared to samples saturated with a pore fluid (water). VT events generated during deformation of water saturated sample are characterised by a distinctive high frequency onset and a longer, low frequency coda exhibiting properties often seen in the field as hybrid events. We present evidence that hybrid events are, in fact, the common type of volcanic seismic event with either VT or low frequency (LF) events representing end members, and whose proportion depend on pore fluid being present in the rock type being deformed, as well as how close the rock is to failure. We find a notable trend of reducing instances of hybrid events leading up to the failure stage in our experiments, suggesting that during this stage, the pore fluid present in the rock moves sufficiently quickly to provide a resonance, seen as a LF coda. Our data supports recent modeling and field studies that postulate that hybrid events generated in volcanic areas are likely to be generated through the interaction of hydrothermal fluids moving through a combination of pre-existing microcrack networks and larger faults, such as those we observe in forensic (post-test) examination.

Bradiarritmia como forma de presentación inusual de rabdomioma cardíaco fetal

The prevalence of fetal heart tumors is 1:10,000 newborns, representing 1% of all cardiac alterations detected during fetal life. Of these, 60% are rhabdomyomas. Distinct clinical onsets have been described for cardiac rhabdomyomas. Fetal bradycardia is an uncommon form of presentation and only three previous cases have been reported. We present the case of a fetal cardiac rhabdomyoma presenting as bradycardia. The newborn was followed up for 24 months.

Survival Profiles of Patients With Frontotemporal Dementia and Motor Neuron Disease

Frontotemporal dementia and amyotrophic lateral sclerosis are neurodegenerative diseases associated with TAR DNA-binding protein 43- and ubiquitin-immunoreactive pathologic lesions. To determine whether survival is influenced by symptom of onset in patients with frontotemporal dementia and amyotrophic lateral sclerosis. Retrospective review of patients with both cognitive impairment and motor neuron disease consecutively evaluated at 4 academic medical centers in 2 countries. Clinical phenotypes and survival patterns of patients. A total of 87 patients were identified, including 60 who developed cognitive symptoms first, 19 who developed motor symptoms first, and 8 who had simultaneous onset of cognitive and motor symptoms. Among the 59 deceased patients, we identified 2 distinct subgroups of patients according to survival. Long-term survivors had cognitive onset and delayed emergence of motor symptoms after a long monosymptomatic phase and had significantly longer survival than the typical survivors (mean, 67.5 months vs 28.2 months, respectively; P < .001). Typical survivors can have simultaneous or discrete onset of cognitive and motor symptoms, and the simultaneous-onset patients had shorter survival (mean, 19.2 months) than those with distinct cognitive or motor onset (mean, 28.6 months) (P = .005). Distinct patterns of survival profiles exist in patients with frontotemporal dementia and motor neuron disease, and overall survival may depend on the relative timing of the emergence of secondary symptoms.

Lattice collapse and the magnetic phase diagram ofSr1−xCaxCo2P2

We report that the 122 type Sr$_{1-x}$Ca$_x$Co$_2$P$_2$ solid solution undergoes an anomalous structural transition from the uncollapsed to the collapsed ThCr$_2$Si$_2$ structure at a distinct onset composition near $x=0.5$. Correlated with the structural changes, the electronic system evolves from a nearly ferromagnetic Fermi liquid to an antiferromagnetic metal, through a complex crossover regime. The structural collapse, driven by P-P bonding across the (Sr,Ca) layers, is much more pronounced in this system than it is in the analogous Fe-based system, indicating a strong sensitivity of structure to total electron count in the transition metal pnictide 122 family.