Patient effort at a glance

A: Patient with little effort. Top: Volume Controlled Ventilation: airway pressure in cmH2O in yellow, constant flow in L/min in pink. Middle: Pressure controlled ventilation: airway pressure in cmH2O in yellow, decelerating flow in L/min in pink. Bottom: Esophageal pressure in cmH2O. B: Patient with high effort. Top: Volume Controlled Ventilation: airway pressure with convex negative deflection during trigger and first half of inspiration (blue arrow). Middle: Pressure controlled ventilation: airway pressure with negative deflection during the trigger (yellow arrow) and slight convex deflection (green arrow), concave deflection in the flow (orange arrow). Bottom: Convex deflection in esophageal pressure (grey arrow).

LUMBOCOSTOVERTEBRAL SYNDROME (LCVS) - A RARE ENTITY

Full term female neonate, weighing 2.7 kg, was born to 37- year-old mother with an uneventful antenatal course. On examination, child was active and anthropometric parameters were normal. Head to toe examination revealed a globular swelling below left costal margin lateral to dorsolumbar spine measuring approximately 6 cm X 6 cm. It was soft, nontender, reducible and used to become prominent on crying. Rest of general and systemic examination was th th normal. X-ray of chest and spine showed dysplastic 9 , 10 , th th th 11 , 12 thoracic vertebrae (Fig 1 red arrow) with absent left 9 , th, th th 10 11 , 12 ribs (Fig 1 blue arrow) and left lumbar hernia (Fig 1 yellow arrow). Ultrasonography abdomen showed a hernial defect in left lumbar region measuring 5 cm X 5 cm containing small bowel loops. Ultrasonography spine showed spina bida occulta. Echocardiography was normal. Lumbar hernia was repaired by pediatric surgeons, operative ndings showed 5 cm X 4 cm hernial sac containing small bowel loops. Child had uneventful post-operative course and discharged successfully. Baby was advised regular follow up.

Reconstructing the origins of the space-number association: spatial and number-magnitude codes must be used jointly to elicit spatially organised mental number lines

In a series of recent studies we have pointed out that the use of contrasting left/right spatial codes, whether indirectly related to number magnitudes through response selection or directly associated to the same magnitudes to guide their spatial positioning on a mental number line, is crucial in eliciting space-number associations (Aiello, 2012; Fattorini et al., 2015; 2016; Pinto et al., 2018). Nonetheless, this conclusion is based on experiments in which spatial and number-magnitudes codes are used jointly during task performance. Here, in a series of unimanual Go/No-Go tasks with intermixed central numerical and pictorial targets, i.e. arrows pointing to the left or to the right, we explore whether spatial codes used in isolation inherently evoke the left-to-right representation of number magnitudes and, vice-versa, whether number-magnitude codes used in isolation inherently evoke the conceptual activation of left/right spatial codes. In a first series of experiments participants were asked to provide unimanual Go/N-Go responses based on instructions that activated only magnitude codes, e.g. “push only if the number is lower than 5 and whenever an arrow appears”, or only spatial codes, e.g. “push only when an arrow points to the left and whenever a number appears”. In a second series of experiments, the same numerical instructions were combined with the request of responding only to arrows in a specific colour, e.g. “push when the number is lower than 5 and whenever a blue arrow appears”. At variance with a recent experiment by Shaki and Fischer (2018), in our experiments no constant association was present between a specific arrow colour and a specific arrow direction. The results of these experiments highlight no space-number congruency effects: e.g. no faster RTs to arrows pointing to the left rather than to the right when participants attend to numbers lower than 5 and, vice-versa, no faster RTs to numbers lower than 5 rather than higher, when participants attend to arrows pointing to the left. Based on these findings it must be concluded that neither space codes used in isolation can elicit a spatial representation of number magnitudes nor number-magnitude codes used in isolation can trigger the activation of spatial codes. Thus, spatial and numerical codes must be used jointly to evoke spatially organised mental number lines.

The impact of bilingualism on executive function in adolescents

Aims and objectives/purpose/research questions: In early childhood and older adulthood, bilinguals generally demonstrate better performance on executive function tasks than their monolingual counterparts, but in the young adult population, these differences are infrequently observed. However, few studies have examined these effects in the adolescent population, so the trajectory of these changes is unclear. The objective of the study was to compare performance on a modified flanker task for monolingual and bilingual adolescents, a time when the executive functions are still developing. Design/methodology/approach: The flanker task was adapted by including a rule-switching component and contained three blocks: (1) rule; (2) flanker; and (3) mixed. In the rule block, a single red or blue arrow (indicated by light grey or medium grey in Figure 1) denoted a response rule; for example, a blue arrow signaled pressing the button indicating the direction the arrow was pointing but a red arrow signaled pressing the button indicating the opposite direction. The flanker block was a standard flanker task consisting of congruent and incongruent trials. The mixed block manipulated both congruency and rule conditions. Data and analysis: Mean reaction times and accuracy from 33 monolingual and 32 bilingual adolescents were analyzed using a repeated-measures analysis of variance with language group as the between-subjects variable and congruency and/or rule-type as the within-subjects variable depending on the block. Findings/conclusions: Bilingual adolescents outperformed monolingual adolescents but only on the block that was most similar to the standard flanker task. The blocks with the rule-switching component yielded equivalent performance. Originality: Unlike previous studies, the current study adapted a simple executive control task to require greater attentional resources by manipulating task demands. Significance/implications: Our findings add to the growing body of literature examining bilingualism and executive control in the adolescent population and fill in the gap in our understanding of the lifespan trajectory of these effects.

Origins of halogen effects in bioorthogonal sydnone cycloadditions

In bioorthogonal sydnone cycloadditions, the fluorine substituent dramatically increases the reactivity of sydnone mainly by lowering its distortion energy (see blue arrow).

Refractory T-Cell Prolymphocytic Leukemia with JAK3 Mutation: In Vitro and Clinical Synergy of Tofacitinib and Ruxolitinib

T-cell prolymphocytic leukemia (T-PLL) is a rare hematologic disease characterized by a T-cell phenotype, rapid progression, and poor prognosis with median survival of less than a year. Alemtuzumab-based chemotherapy has increased the rate of complete remissions but these are often short-lived and allogeneic transplant is considered the only curative therapy. In recent studies, JAK3 activating mutations have been identified in T-cell cancers, with T-PLL having the highest rate of JAK3 mutations (30 - 42%). As such, T-PLL is a model disease for evaluating the utility of JAK3 inhibitors. We present a case of a 64 year old man with relapsed-refractory T-PLL. He was initially treated with alemtuzumab and obtained complete response and was consolidated with matched unrelated donor stem cell transplant. His disease stayed in remission for approximately 1.5 years before relapse, which was then treated with a clinical trial of romedepsin-lenalidomide (partial responses then progression at 6 months) and later alemtuzumab. Due to complications of myelosuppression and CMV reactivation, his treatment was interrupted leading to disease progression (Figure 1). The doubling time of lymphocyte count was approximately 20 days and over a span of 60 days the lymphocyte count rose from 8 x 109/L to 68 x 109/L. Exon sequencing showed a JAK3 mutation. The patient consented to and was treated with FDA-approved tofacitinib (initially 5 mg BID, increased to 10 mg BID after 15 days of treatment). An initial decrease in lymphocyte count was followed by progression. In vitro treatment of the patient's cells showed modest effects of tofacitinib and ruxolitinib as single agents, in the range of doxorubicin, but synergy between the agents (Figure 2). After 40 days of treatment with tofacitinib and with a lymphocyte count of 150 x 109/L, ruxolitinib (5mg BID) was added. Over the 60 days since dual inhibition was started, the lymphocyte count has stabilized. The patient has remained completely asymptomatic during treatment with tofacitinib and ruxolitinib. Neutrophil count has remained normal. Platelet count and hemoglobin have however declined from ~50 x109/L to ~30 x109/L and from 11 g/dL to 8.1 g/dL respectively, since the introduction of ruxolitinib. The stabilization in lymphocyte count confirms the clinical activity of JAK inhibitors in T-PLL as suggested by the presence of JAK3 mutations and by in-vitro assays. It also suggests clinical synergy between ruxolitinib and tofacitinib in this setting. Prospective studies of JAK inhibitors in PLL patients with formal dose-finding studies are needed. Figure 1. The overall trend of lymphocytes following disease refractory to or complicated by multiple lines of treatment. The patient demonstrated rapidly rising LDH and lymphocyte count. Following administration of tofacitinib (red arrow) and ruxolitinib (blue arrow), lymphocyte counts stabilized. Figure 1. The overall trend of lymphocytes following disease refractory to or complicated by multiple lines of treatment. The patient demonstrated rapidly rising LDH and lymphocyte count. Following administration of tofacitinib (red arrow) and ruxolitinib (blue arrow), lymphocyte counts stabilized. Figure 2. Level of ATP in patient cells treated for 24 hours with control, tofacitinib (tof), ruxolitinib (ruxol), doxorubicin or a combination of tofacitinib and ruxolitinib. There is synergistic depression of cell metabolism and growth for cells treated with both tofacitinib and ruxolitinib. Figure 2. Level of ATP in patient cells treated for 24 hours with control, tofacitinib (tof), ruxolitinib (ruxol), doxorubicin or a combination of tofacitinib and ruxolitinib. There is synergistic depression of cell metabolism and growth for cells treated with both tofacitinib and ruxolitinib. Disclosures Off Label Use: Jak inhibitors in TCL. van Besien:Miltenyi Biotec: Research Funding.