Anti-D in a mother, hemizygous for the variant RHD*DNB gene, associated with hemolytic disease of the fetus and newborn.

BACKGROUND: Individuals with the partial D phenotype when exposed to D+ red blood cells (RBCs) carrying the epitopes they lack may develop anti-D specific for the missing epitopes. DNB is the most common partial D in Caucasians and the clinical significance for anti-D in these individuals is unknown. STUDY DESIGN AND METHODS: This article describes the serologic genotyping results and clinical manifestations in two group D+ babies of a mother presenting as group O, D+ with alloanti-D. RESULTS: The mother was hemizygous for RHD*DNB gene and sequencing confirmed a single-nucleotide change at c.1063G>A. One baby (group A, D+) displayed bilirubinemia at birth with a normal hemoglobin level. Anti-A and anti-D were eluted from the RBCs. For the next ongoing pregnancy, the anti-D titer increased from 32 to 256. On delivery the baby typed group O and anti-D was eluted from the RBCs. This baby at birth exhibited anemia, reticulocytosis, and hyperbilirubinemia requiring intensive phototherapy treatment from Day 0 to Day 9 after birth and was discharged on Day 13. Intravenous immunoglobulin was also administered. Both babies were heterozygous for RHD and RHD*DNB. CONCLUSION: The anti-D produced by this woman with partial D DNB resulted in a case of hemolytic disease of the fetus and newborn (HDFN) requiring intensive treatment in the perinatal period. Anti-D formed by women with the partial D DNB phenotype has the potential to cause HDFN where the fetus is D+. Women carrying RHD*DNB should be offered appropriate prophylactic anti-D and be transfused with D- RBCs if not already alloimmunized.

Mechanisms of automaticity and anticipatory control in fluid intelligence.

The constructs of fluid (Gf) and crystalized (Gc) intelligence represent an early attempt to describe the mechanisms of problem solving in the vertebrate brain. Modern neuroscience demonstrates that problem solving involves interplay between the mechanisms of automaticity and anticipatory control, enabling nature's elegant solution to the challenges animals face in their environment. Studies of neural functioning are making clear the primary role of cortical-subcortical interactions in the manifestation of intelligent behavior in humans and other vertebrates. A tridimensional model of intelligent problem solving is explored, wherein the basal ganglia system (BGS) and cerebrocerebellar system (CCS) interact within large scale brain networks. The BGS and CCS work together to enable automaticity to occur. The BGS enables the organism to learn what to do through a powerful instrumental learning system. The BGS also regulates when behavior is released through an inhibitory system which is incredibly sensitive to context. The CCS enables the organism to learn how to perform adaptive behaviors. Internal cerebellar models enable gradual improvements in the quality of behavioral output. The BGS and CCS interact within large scale brain networks, including the dorsal attention network (DAN), ventral attention network (VAN), default mode network (DMN) and frontoparietal network (FPN). The interactions of these systems enable vertebrate organisms to develop a vast array of complex adaptive behaviors. The benefits and importance of developing clinical tests to measure the integrity of these systems is considered.

Hemolytic transfusion reaction attributable to anti-Dia.

CONCLUSIONS: In situations when a patient's antibody detection test is negative, many institutions have moved from an indirect antiglobulin test (IAT) crossmatch to an electronic crossmatch system. Here we report a case of an acute hemolytic transfusion reaction attributable to anti-Dia in a patient with a negative antibody detection test. A 22-year-old female patient with a diagnosis of ß thalassemia and sickle cell anemia commenced a routine exchange transfusion of 5 units of red blood cells (RBCs) in the apheresis unit as part of her regular treatment. When the patient started receiving the implicated unit, she reported back pain, chest pain, and a feeling of anxiety, suggestive of an acute transfusion reaction. The transfusion was ceased and an investigation of an adverse event was commenced. This case illustrates that the presence of antibodies to low-prevalence antigens remains a significant issue for transfusion-dependent individuals. To prevent other transfusion reactions by anti-Dia, the addition of Di(a+) cells to the reagent RBCs used for the antibody detection test along with IAT-crossmatching of donor units for all patients with sickle cell disease is recommended.

Implicit Working Memory: Implications for Assessment and Treatment.

Working memory (WM) impacts a gamut of cognitive abilities, but implicit WM is typically not considered in assessment or treatment, which may explain the variability of results in reviews of WM training. The role of implicit WM in adaptive behavior is reviewed. All we do is action based. Explicit WM plays a major role when we are required to "think"; that is, when we apply previously learned perception-action linkages in new ways to unique situations. Implicit WM is involved in the automation of behavior, which occurs through interaction with cortical and subcortical systems that guide sensory-motor anticipation and the prediction of reward. This article reviews evidence that implicit WM interacts with cortical-cerebellar and cortical-basal ganglia connections to form perception-action linkages. The cerebellum forms an internal model of cortical WM, corrects the content of this internal model, and then projects the improved representation back to the cortex, where it is retained for future use. The basal ganglia also form an anticipatory system, controlling cortical access to WM by allowing or restricting the information that is released based on the probability of reward. This framework is applied to the assessment and treatment of individuals with WM deficits. The ability to automate behavior can be assessed through repeated trials of existing testing instruments, such as the Trails B and Stroop tasks. Application of skill learning emphasizing automation as an end goal offers a model for the development of new types of WM training.

The role of the thalamus in ADHD symptomatology and treatment.

Attention-deficit hyperactivity disorder (ADHD) is a chronic disorder with symptoms of inattention and impulsivity that partially remit with age. A review of longitudinal studies of children and adolescents with ADHD showed that the majority will have continued cognitive and functional impairments into adulthood. The thalamus likely plays a prominent role in ADHD symptomatology, based on evidence that the thalamus generates waking-state electroencephalography (EEG) rhythms along with extensive thalamic neural circuitry connections with cortical and subcortical areas. Research demonstrates a specific abnormality in the thalamic pulvinar nucleus in ADHD populations. The thalamus can also play a role in ADHD treatment, based on solid evidence that both animals and humans can learn to self-regulate EEG oscillations. Given the underarousal and sleep disturbance commonly seen in ADHD, along with data that indicate an increased dosage of ADHD medication may improve behavioral control at a cost of lowered cognitive functioning, further investigation of the role for self-regulation through EEG training is warranted.

Attention: an evolving construct.

We review the implications of large-scale brain systems on the construct of attention by first focusing on significant theories and discoveries during the previous 150 years and then considering how the comparatively recent discovery of large-scale brain systems may render previous conceptualizations of attention outdated. Seven functional brain networks are briefly reviewed and the implications of emerging principles of brain functioning for test construction and neuropsychological evaluation are considered. To remain a relevant discipline moving into the 21st century, the field of neuropsychology needs to apply the principles that have been discovered about brain networks to better inform our understanding of attention as well as our ever-refining evaluation of this construct.

Structure and function of large-scale brain systems.

This article introduces the functional neuroanatomy of large-scale brain systems. Both the structure and functions of these brain networks are presented. All human behavior is the result of interactions within and between these brain systems. This system of brain function completely changes our understanding of how cognition and behavior are organized within the brain, replacing the traditional lesion model. Understanding behavior within the context of brain network interactions has profound implications for modifying abstract constructs such as attention, learning, and memory. These constructs also must be understood within the framework of a paradigm shift, which emphasizes ongoing interactions within a dynamically changing environment.

The small-world organization of large-scale brain systems and relationships with subcortical structures.

Brain structure and function is characterized by large-scale brain systems. However, each system has its own "small-world" organization, with sub-regions, or "hubs," that have varying degrees of specialization for certain cognitive and behavioral processes. This article describes this small-world organization, and the concepts of functional specialization and functional integration are defined and explained through practical examples. We also describe the development of large-scale brain systems and this small-world organization as a sensitive, protracted process, vulnerable to a variety of influences that generate neurodevelopmental disorders.

Large-scale brain systems and subcortical relationships: the vertically organized brain.

This article reviews the vertical organization of the brain. The cortico-basal ganglia and the cerebro-cerebellar circuitry systems are described as fundamental to cognitive and behavioral control. The basal ganglia anticipate and guide implicitly learned behaviors on the basis of experienced reward outcomes. The cerebellar-cortical network anticipates sensorimotor outcomes, allowing behaviors to be adapted across changing settings and across contexts. These vertically organized systems, operating together, represent the underpinning of cognitive control. The medial temporal lobe system, and its development, is also reviewed in order to better understand how brain systems interact for both implicit and explicit cognitive control.

Large-scale brain systems and subcortical relationships: practical applications.

This article describes an interactive paradigm for understanding brain functioning. This model requires both explicit and implicit learning processes. This paradigm is illustrated through the interpretation of practical examples of behavior. Applications of current neuropsychological tests are presented within this interactive paradigm. The development of new neuropsychological tests is presented, as derived from experimental test paradigms that evaluate implicit learning processes.

The neuropsychology of attention: revisiting the "Mirsky model".

Nearly 25 years ago, Mirsky and colleagues proposed a multiple-component model of attention. It was proposed that attention was characterized by several distinct elements that were organized into a system. A putative neuroanatomical substrate of this model of attention was proposed. This functional anatomy was primarily based upon inferences derived from brain lesion studies. Mirsky and colleagues developed a systematic clinical evaluation of this model by applying a group of neuropsychological tests. Since the introduction of what has been commonly referred to as the "Mirsky model," significant advances have been made in our understanding of brain-behavior relationships. This article applies current neuroscientific principles to "update" our understanding of attention and the "Mirsky model." We also demonstrate how the interpretation of neuropsychological tests can be modified according to principles of large-scale brain systems and patterns of brain network functional connectivity.

Neuropsychological assessment of persons with physical disability, visual impairment or blindness, and hearing impairment or deafness.

Conducting assessment with individuals with physical disability, visual impairment or blindness, and hearing impairment or deafness poses significant challenges for the neuropsychologist. Although standards for psychological testing have been devised to address assessment of persons with disabilities, little research has been conducted to validate neuropsychological test accommodation and modification practices that deviate from standard test administration or to develop test parameters and interpretive guidelines specifically for persons with different physical or sensory disabilities. This paper reviews issues pertaining to neuropsychological test selection and administration, common accommodation and modification practices, test development and validation, and disability-related factors that influence interpretation of test results. Systematic research is needed to develop methodological parameters for testing and to ensure reliable and valid neuropsychological assessment practices for individuals with physical or sensory disabilities.